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Archive for the ‘Cancer and Current Therapeutics’ Category


Reporter and Curator: Dr. Sudipta Saha, Ph.D.

 

A mutated gene called RAS gives rise to a signalling protein Ral which is involved in tumour growth in the bladder. Many researchers tried and failed to target and stop this wayward gene. Signalling proteins such as Ral usually shift between active and inactive states.

 

So, researchers next tried to stop Ral to get into active state. In inacvtive state Ral exposes a pocket which gets closed when active. After five years, the researchers found a small molecule dubbed BQU57 that can wedge itself into the pocket to prevent Ral from closing and becoming active. Now, BQU57 has been licensed for further development.

 

Researchers have a growing genetic data on bladder cancer, some of which threaten to overturn the supposed causes of bladder cancer. Genetics has also allowed bladder cancer to be reclassified from two categories into five distinct subtypes, each with different characteristics and weak spots. All these advances bode well for drug development and for improved diagnosis and prognosis.

 

Among the groups studying the genetics of bladder cancer are two large international teams: Uromol (named for urology and molecular biology), which is based at Aarhus University Hospital in Denmark, and The Cancer Genome Atlas (TCGA), based at institutions in Texas and Boston. Each team tackled a different type of cancer, based on the traditional classification of whether or not a tumour has grown into the muscle wall of the bladder. Uromol worked on the more common, earlier form, non-muscle-invasive bladder cancer, whereas TCGA is looking at muscle-invasive bladder cancer, which has a lower survival rate.

 

The Uromol team sought to identify people whose non-invasive tumours might return after treatment, becoming invasive or even metastatic. Bladder cancer has a high risk of recurrence, so people whose non-invasive cancer has been treated need to be monitored for many years, undergoing cystoscopy every few months. They looked for predictive genetic footprints in the transcriptome of the cancer, which contains all of a cell’s RNA and can tell researchers which genes are turned on or off.

 

They found three subgroups with distinct basal and luminal features, as proposed by other groups, each with different clinical outcomes in early-stage bladder cancer. These features sort bladder cancer into genetic categories that can help predict whether the cancer will return. The researchers also identified mutations that are linked to tumour progression. Mutations in the so-called APOBEC genes, which code for enzymes that modify RNA or DNA molecules. This effect could lead to cancer and cause it to be aggressive.

 

The second major research group, TCGA, led by the National Cancer Institute and the National Human Genome Research Institute, that involves thousands of researchers across USA. The project has already mapped genomic changes in 33 cancer types, including breast, skin and lung cancers. The TCGA researchers, who study muscle-invasive bladder cancer, have looked at tumours that were already identified as fast-growing and invasive.

 

The work by Uromol, TCGA and other labs has provided a clearer view of the genetic landscape of early- and late-stage bladder cancer. There are five subtypes for the muscle-invasive form: luminal, luminal–papillary, luminal–infiltrated, basal–squamous, and neuronal, each of which is genetically distinct and might require different therapeutic approaches.

 

Bladder cancer has the third-highest mutation rate of any cancer, behind only lung cancer and melanoma. The TCGA team has confirmed Uromol research showing that most bladder-cancer mutations occur in the APOBEC genes. It is not yet clear why APOBEC mutations are so common in bladder cancer, but studies of the mutations have yielded one startling implication. The APOBEC enzyme causes mutations early during the development of bladder cancer, and independent of cigarette smoke or other known exposures.

 

The TCGA researchers found a subset of bladder-cancer patients, those with the greatest number of APOBEC mutations, had an extremely high five-year survival rate of about 75%. Other patients with fewer APOBEC mutations fared less well which is pretty surprising.

 

This detailed knowledge of bladder-cancer genetics may help to pinpoint the specific vulnerabilities of cancer cells in different people. Over the past decade, Broad Institute researchers have identified more than 760 genes that cancer needs to grow and survive. Their genetic map might take another ten years to finish, but it will list every genetic vulnerability that can be exploited. The goal of cancer precision medicine is to take the patient’s tumour and decode the genetics, so the clinician can make a decision based on that information.

 

References:

 

https://www.ncbi.nlm.nih.gov/pubmed/29117162

 

https://www.ncbi.nlm.nih.gov/pubmed/27321955

 

https://www.ncbi.nlm.nih.gov/pubmed/28583312

 

https://www.ncbi.nlm.nih.gov/pubmed/24476821

 

https://www.ncbi.nlm.nih.gov/pubmed/28988769

 

https://www.ncbi.nlm.nih.gov/pubmed/28753430

 

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Lectures by The 2017 Award Recipients of Warren Alpert Foundation Prize in Cancer Immunology, October 5, 2017, HMS, 77 Louis Paster, Boston

Top, from left: James Allison and Lieping Chen. Bottom, from left: Gordon Freeman, Tasuku Honjo (NOT ATTENDED), Arlene Sharpe.

Aviva Lev-Ari, PhD, RN was in attendance and covered this event LIVE

 

The 2017 Warren Alpert Foundation Prize has been awarded to five scientists for transformative discoveries in the field of cancer immunology.

Collectively, their work has elucidated foundational mechanisms in cancer’s ability to evade immune recognition and, in doing so, has profoundly altered the understanding of disease development and treatment. Their discoveries have led to the development of effective immune therapies for several types of cancer.

The 2017 award recipients are:

  • James Allison, professor of immunology and chair of the Department of Immunology, The University of Texas MD Anderson Cancer Center – Immune checkpoint blockage in Cancer Therapystrictly Genomics based drug
  1. 2017 FDA approved a gemonics based drug
  2. and co-stimulatory signals
  3. CTLA-4 blockade, CD28, AntiCTLA-4 induceses regression of Transplantable Murine tumo
  4. enhance tumor-specific immune response
  5. Fully antibody human immune response in 10,000 patients – FDA approved 2011
  6. Metastatic melanoma – 3 years survival, programmed tumor death, PD-1, MHC-A1
  7. Ipi/Nivo vs. Ipi – combination – 60% survival vs Ipi alone
  8. Anti CTA4 va Anti-PD-1
  9. responsive T cell population – MC38 TILs
  10. MC38 Infiltrating T cell populations: Treg, CD4, Effector, CD8, NKT/gamma-delta
  11. Checkpoint blockage modulates infiltrating T cell population frequencies
  12. T reg correlated with Tumor growth
  13. Combination therapy lead to CURE survival at 80% rate vs CTAL-4 40% positive outcome

Not Attended — Tasuku Honjo, professor of immunology and genomic medicine, Kyoto University – Immune regulation of Cancer Therapy by PD-1 Blockade

 

  • Lieping Chen, United Technologies Corporation Professor in Cancer Research and Professor of immunobiology, of dermatology and of medicine, Yale University – Adoptive Resistance: Molecular Pathway t Cancer Therapy – focus on solid tumors
  1. Enhancement – Enhance normal immune system – Co-stimulation/Co-inhibition Treg, and Cytokines, adoptive cell therapy, Lymphoid organs stores
  2. Normalization – to correct defective immune system – normalizing tumor immunity, diverse tumor escape mechanisms
  3. Anti-PD therapy: regression of large solid tumors: normalizing tumor immunity targeting tumor microenvironment: Heterogeneity, functional modulation, cellular and molecular components – classification by LACK of inflamation, adaptive resistance, other inhibitory pathways, intrinsic induction
  4. avoid autoimmune toxicity,
  5. Resetting immune response (melanoma)
  6. Understad Resistance: Target missing resistance or Adaptive resistance Type II= acquired immunity
  • Gordon Freeman, professor of medicine, Dana-Farber Cancer Institute, Harvard Medical School – PD-L1/PD-1 Cancer Immunotherapy
  1. B7 antibody
  2. block pathway – checkpoint blockage, Expand the T cells after recognition of the disease. T cell receptor signal, activation, co -stimulatory: B71 molecule, B72 – survival signals and cytokine production,.Increased T cell proliferation,
  3. PDL-1 is a ligand of PD 1. How T cell die? genes – PD1 Gene was highly expressed,
  4. Interferon gamma upregulate PD-L1 expression
  5. Feedback loop Tumor – stimulating immune response, interferon turn off PD1
  6. PD-L1 and PD-L2 Expression: Interferom
  7. Trancefuctor MHC, B7-2
  8. PD-L! sisgnat inhibit T-cell activation: turn off Proliferation and cytokine production — Decreasing the immune response
  9. T cell DNA Content: No S-phase devided cell
  10. PD-L1 engagement of PD-1 results in activation : Pd-1 Pathway inhibits T Cell Actiivation – lyposite motility,
  11. Pd-L2 is a second ligand for PD-1 and inhibits T cell activation
  12. PDl-1 expression: BR CA, Ovarian, Colonol-rectal, tymus, endothelial
  13. Blockage of the Pathway – Immune response enhanced
  14. Dendritic cells express PD-L1, PD-L2 and combination of Two, Combination was best of all by increase of cytokine production, increasing the immune response.
  15. PD-L1 blockade enhanced the immune response , increase killing and increased production of cytokines,
  16. anti-tumor efficacy of anti-PD-1/Pd-L1
  17. Pancreatic and colono-rector — PD-L, PDL1, PDL2 — does not owrkd.
  18. In menaloma: PD-1 works better than CYLA-4
  19. Comparison of Targeted Therapy: BRAF TKI vs Chemo high % but short term
  20. Immunotherapy – applies several mechanism: pre-existing anti-therapy
  21. Immune desert: PD=L does not work for them
  22. COMBINATION THERAPY: BLOCK TUMOR INVASION THEN STIMULATE IMMUNE RESPONSE — IT WILL WORK
  23. PD blockage + nutrients and probiotic
  24. Tumor Genome Therapy
  25. Tumore Immuno-evasion Score
  26. Antigens for immune response – choose the ones
  27. 20PD-1 or PD-L1 drugs in development
  28. WHO WILL THE DRUG WORK FOR?

 

  • Arlene Sharpe, the George Fabyan Professor of Comparative Pathology, Harvard Medical School; senior scientist, department of pathology, Brigham and Women’s Hospital – Multi-faceted Functionsof the PD-1 Pathway
  1. function of the pathway: control T cell activation and function of maintain immune tolerance
  2. protect tissues from damage by immune response
  3. T cell dysfunction during cancer anf viral infection
  4. protection from autoimmunity, inflammation,
  5. Mechanism by which PD-1 pathway inhibits anti-tumor immunity
  6. regulation of memoryT cell responce of PD-1
  7. PD-1 signaling inhibit anti-tumor immunity
  8. Compare: Mice lacking CD8-Cre- (0/5) cleared vs PD-1-/-5/5 – PD-1 DELETION: PARTIAL AND TIMED: DELETION OF PD-1 ON HALF OG TILS STARTING AT DAY 7 POSTTUMOR IMPLANTATION OF BOTH PD-1 AND PD-1 TILS: – Tamoxifen days 7-11
  9. Transcription profile: analysis of CD8+ TILs reveal altered metabolism: Fatty Acid Metabolism vs Oxidative Phosphorylation
  10. DOes metabolic shift: WIld type mouth vs PD-1-/_ P14: analyze Tumor cell killingPD-1-/- enhanced FAO increases CD8+ T cell tocicity
  11. Summary: T cell memory development and PD-1: T effectors vs T cell memory: Primary vs Secondary infection: In the absent of PD-1, CD8+ T cels show increase expansion of T cells
  12. INFLUENZA INFECTION: PRIMARY more virus in lung in PD-1 is lacking
  13. Acute infection: PD-1 controls memory T cell differentiation vs PD-1 increase expansion during effector phase BUT impaired persistence during memory phase: impaired cytokine production post re-challenge
  14. PD-1 immunotherapy work for patients with tumor: Recall Response and Primary response
  15. TIL density Primary vs Long term survivor – 5 days post tumor implantation – rechallenged long term survival
  16. Hot tumor vs Cold tumor – Deletion of PD-1 impairs T memory cell development

 

Opening Remarks: George Q. Daley, MD, PhD, DEAN, HMS

  • Scientific collaboration check point – avoid the body attacking itself, sabotaging the immune system
  • 1987 – Vaccine for HepB
  • Eight of the awardees got the Nobel Prize

 

Moderated by Joan Brugge, PhD, HMS, Prof. of Cell Biology

  • Evolution of concepts of Immunotherapy: William Coley’s Toxin streptoccocus skin infection.
  • 20th century: Immuno-surveilence, Immune response – field was dead in 1978 replaced by Immunotherapy
  • Rosenberg at NIH, high dose of costimulatory molecule prevented tumor reappearanceantbody induce tumor immunity–>> immune theraphy by check point receptor blockade – incidence of tumor in immune compromised mice – transfer T cell
  • T cell defficient, not completely defficient, self recognition of tumor,
  • suppress immmune – immune evasion
  • Michael Atkins, MD, Detupy Director, Georgetown-Lombardi, Comprehensive Cancer Center Clinical applications of Checkpoint inhibitors: Progress and Promise
  1. Overwhelm the Immune system, hide, subvert, Shield, defend-deactivating tumor trgeting T cells that ATTACK the immune system
  2. Immune system to TREAT the cancer
  3. Monotherapy – anti PD1/PD-L1: Antagonist activity
  4. Evading immune response: prostate, colcn
  5. MMR deficiency
  6. Nivolumab in relaped/Refractory HODGKIN LYMPHOMAS – over expression of PD-L1 and PDL2in Lymphomas
  7. 18 month survival better with Duv in Lung cancer stage 3 – anti PD-1- adjuvant therapy with broad effectiveness
  8. Biomarkers for pD-L1 Blockage
  9. ORR higher in PD-L1
  10. Improve Biomarkers: Clonality of T cells in Tumors
  11. T-effector Myeloid Inflammation Low – vs Hogh:
  12. Biomarker Model: Neoantigen burden vs Gene expression vs CD8+
  13. Tissue DIagnostic Labs: Tumor microenveironmenr
  14. Microbiome
  15. Combination: Nivo vs Nivo+Ipi is superior: DETERMINE WHEN TO STOP TREATMENT
  16. 15/16 stopped treatment – Treatment FREE SURVIVAL
  17. Sequencing with Standard Therapies
  18. Brain metastasis – Immune Oncology Therapy – crosses the BBB
  19. Less Toxic regimen, better toxicity management,
  20. Use Immuno therapy TFS
  21. combination – survival must be justified
  22. Goal: to make Cancer a curable disease vs cancer becoming a CHronic disease

 

Closing Remarks: George Q. Daley, MD, PhD, DEAN, HMS

 

The honorees will share a $500,000 prize and will be recognized at a day-long symposium on Oct. 5 at Harvard Medical School.

The Warren Alpert Foundation, in association with Harvard Medical School, honors trailblazing scientists whose work has led to the understanding, prevention, treatment or cure of human disease. The award recognizes seminal discoveries that hold the promise to change our understanding of disease or our ability to treat it.

“The discoveries honored by the Warren Alpert Foundation over the years are remarkable in their scope and potential,” said George Q. Daley, dean of Harvard Medical School. “The work of this year’s recipients is nothing short of breathtaking in its profound impact on medicine. These discoveries have reshaped our understanding of the body’s response to cancer and propelled our ability to treat several forms of this recalcitrant disease.”

The Warren Alpert Foundation Prize is given internationally. To date, the foundation has awarded nearly $4 million to 59 scientists. Since the award’s inception, eight honorees have also received a Nobel Prize.

“We commend these five scientists. Allison, Chen, Freeman, Honjoand Sharpe are indisputable standouts in the field of cancer immunology,” said Bevin Kaplan, director of the Warren Alpert Foundation. “Collectively, they are helping to turn the tide in the global fight against cancer. We couldn’t honor more worthy recipients for the Warren Alpert Foundation Prize.”

The 2017 award: Unraveling the mysterious interplay between cancer and immunity

Understanding how tumor cells sabotage the body’s immune defenses stems from the collective work of many scientists over many years and across multiple institutions.

Each of the five honorees identified key pieces of the puzzle.

The notion that cancer and immunity are closely connected and that a person’s immune defenses can be turned against cancer is at least a century old. However, the definitive proof and demonstration of the steps in this process were outlined through findings made by the five 2017 Warren Alpert prize recipients.

Under normal conditions, so-called checkpoint inhibitor molecules rein in the immune system to ensure that it does not attack the body’s own cells, tissues and organs. Building on each other’s work, the five award recipients demonstrated how this normal self-defense mechanism can be hijacked by tumors as a way to evade immune surveillance and dodge an attack. Subverting this mechanism allows cancer cells to survive and thrive.

A foundational discovery made in the 1980s elucidated the role of a molecule on the surface of T cells, the body’s elite assassins trained to seek, spot and destroy invaders.

A protein called CTLA-4 emerged as a key regulator of T cell behavior—one that signals to T cells the need to retreat from an attack. Experiments in mice lacking CTLA-4 and use of CTLA-4 antibodies demonstrated that absence of CTLA-4 or blocking its activity could lead to T cell activation and tumor destruction.

Subsequent work identified a different protein on the surface of T cells—PD-1—as another key regulator of T cell response. Mice lacking this protein developed an autoimmune disease as a result of aberrant T cell activity and over-inflammation.

Later on, scientists identified a molecule, B7-H1, subsequently renamed PD-L1, which binds to PD-1, clicking like a key in a lock. This was followed by the discovery of a second partner for PD-1—the molecule PD-L2—which also appeared to tame T-cell activity by binding to PD-1.

The identification of these molecules led to a set of studies showing that their presence on human and mouse tumors rendered the tumors resistant to immune eradication.

A series of experiments further elucidated just how tumors exploit the interaction between PD-1 and PD-L1 to survive. Specifically, some tumor cells appeared to express PD-L1, essentially “wrapping” themselves in it to avoid immune recognition and destruction.

Additional work demonstrated that using antibodies to block this interaction disarmed the tumors, rendering them vulnerable to immune destruction.

Collectively, the five scientists’ findings laid the foundation for antibody-based therapies that modulate the function of these molecules as a way to unleash the immune system against cancer cells.

Antibody therapy that targets CTLA-4 is currently approved by the FDA for the treatment of melanoma. PD-1/PD-L1 inhibitors have already shown efficacy in a broad range of cancers and have been approved by the FDA for the treatment of melanoma; kidney; lung; head and neck cancer; bladder cancer; some forms of colorectal cancer; Hodgkin lymphoma and Merkel cell carcinoma.

In their own words

“I am humbled to be included among the illustrious scientists who have been honored by the Warren Alpert Foundation for their contributions to the treatment and cure of human disease in its 30+ year history.  It is also recognition of the many investigators who have labored for decades to realize the promise of the immune system in treating cancer.”
        -James Allison


“The award is a great honor and a wonderful recognition of our work.”
         Lieping Chen



I am thrilled to have made a difference in the lives of cancer patients and to be recognized by fellow scientists for my part in the discovery of the PD-1/PD-L1 and PD-L2 pathway and its role in tumor immune evasion.  I am deeply honored to be a recipient of the Alpert Award and to be recognized for my part in the work that has led to effective cancer immunotherapy. The success of immunotherapy has unleashed the energies of a multitude of scientists to further advance this novel strategy.”
                                        -Gordon Freeman


I am extremely honored to receive the Warren Alpert Foundation Prize. I am very happy that our discovery of PD-1 in 1992 and subsequent 10-year basic research on PD-1 led to its clinical application as a novel cancer immunotherapy. I hope this development will encourage many scientists working in the basic biomedical field.”
-Tasuku Honjo


“I am truly honored to be a recipient of the Alpert Award. It is especially meaningful to be recognized by my colleagues for discoveries that helped define the biology of the CTLA-4 and PD-1 pathways. The clinical translation of our fundamental understanding of these pathways illustrates the value of basic science research, and I hope this inspires other scientists.”
-Arlene Sharpe

Previous winners

Last year’s award went to five scientists who were instrumental in the discovery and development of the CRISPR bacterial defense mechanism as a tool for gene editing. They were RodolpheBarrangou of North Carolina State University, Philippe Horvath of DuPont in Dangé-Saint-Romain, France, Jennifer Doudna of the University of California, Berkeley, Emmanuelle Charpentier of the Max Planck Institute for Infection Biology in Berlin and Umeå University in Sweden, and Virginijus Siksnys of the Institute of Biotechnology at Vilnius University in Lithuania.

Other past recipients include:

  • Tu Youyou of the China Academy of Chinese Medical Science, who went on to receive the 2015 Nobel Prize in Physiology or Medicine with two others, and Ruth and Victor Nussenzweig, of NYU Langone Medical Center, for their pioneering discoveries in chemistry and parasitology of malaria and the translation of their work into the development of drug therapies and an anti-malarial vaccine.
  • Oleh Hornykiewicz of the Medical University of Vienna and the University of Toronto; Roger Nicoll of the University of California, San Francisco; and Solomon Snyder of the Johns Hopkins University School of Medicine for research into neurotransmission and neurodegeneration.
  • David Botstein of Princeton University and Ronald Davis and David Hogness of Stanford University School of Medicine for contributions to the concepts and methods of creating a human genetic map.
  • Alain Carpentier of Hôpital Européen Georges-Pompidou in Paris and Robert Langer of MIT for innovations in bioengineering.
  • Harald zur Hausen and Lutz Gissmann of the German Cancer Research Center in Heidelberg for work on the human papillomavirus (HPV) and cancer of the cervix. Zur Hausenand others were honored with the Nobel Prize in Physiology or Medicine in 2008.

The Warren Alpert Foundation

Each year the Warren Alpert Foundation receives between 30 and 50 nominations from scientific leaders worldwide. Prize recipients are selected by the foundation’s scientific advisory board, which is composed of distinguished biomedical scientists and chaired by the dean of Harvard Medical School.

Warren Alpert (1920-2007), a native of Chelsea, Mass., established the prize in 1987 after reading about the development of a vaccine for hepatitis B. Alpert decided on the spot that he would like to reward such breakthroughs, so he picked up the phone and told the vaccine’s creator, Kenneth Murray of the University of Edinburgh, that he had won a prize. Alpert then set about creating the foundation.

To award subsequent prizes, Alpert asked Daniel Tosteson (1925-2009), then dean of Harvard Medical School, to convene a panel of experts to identify scientists from around the world whose research has had a direct impact on the treatment of disease.

SOURCE

https://hms.harvard.edu/news/warren-alpert-foundation-honors-pioneers-cancer-immunology

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Koch Institute Immune Engineering Symposium on October 16 & 17, 2017, Kresge, MIT

Reporter: Aviva Lev-Ari, PhD, RN

 

Koch Institute Immune Engineering Symposium on October 16 & 17, 2017.

 

Summary: Biological, chemical, and materials engineers are engaged at the forefront of immunology research. At their disposal is an analytical toolkit honed to solve problems in the petrochemical and materials industries, which share the presence of complex reaction networks, and convective and diffusive molecular transport. Powerful synthetic capabilities have also been crafted: binding proteins can be engineered with effectively arbitrary specificity and affinity, and multifunctional nanoparticles and gels have been designed to interact in highly specific fashions with cells and tissues. Fearless pursuit of knowledge and solutions across disciplinary boundaries characterizes this nascent discipline of immune engineering, synergizing with immunologists and clinicians to put immunotherapy into practice.

SPEAKERS:

Michael Birnbaum – MIT, Koch Institute

Arup Chakraborty – MIT, Insititute for Medical Engineering & Sciences

Jianzhu Chen – MIT, Koch Institute

Jennifer R. Cochran – Stanford University

Jennifer Elisseeff – Johns Hopkins University

K. Christopher Garcia – Stanford University

George Georgiou – University of Texas at Austin

Darrell Irvine – MIT, Koch Institute

Tyler Jacks – MIT, Koch Institute

Doug Lauffenburger – MIT, Biological Engineering and Koch Institute

Wendell Lim – University of California, San Francisco

Harvey Lodish – Whitehead Institute and Koch Institute

Marcela Maus – Massachusetts General Hospital

Garry P. Nolan – Stanford University

Sai Reddy – ETH Zurich

Nicholas Restifo – National Cancer Institute

William Schief – The Scripps Research Institute

Stefani Spranger – MIT, Koch Institute

Susan Napier Thomas – Georgia Institute of Technology

Laura Walker – Adimab, LLC

Jennifer Wargo – MD Anderson Cancer Center

Dane Wittrup – MIT, Koch Institute

Kai Wucherpfennig – Dana-Farber Cancer Institute

Please contact ki-events@mit.edu with any questions.

SOURCE

From: Koch Institute Immune Engineering Symposium <ki-events@mit.edu>

Reply-To: <ki-events@mit.edu>

Date: Friday, September 8, 2017 at 9:06 AM

To: Aviva Lev-Ari <AvivaLev-Ari@alum.berkeley.edu>

Subject: Reminder – Register Today

 

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New Treatment in Development for Glioblastoma: Hopes for Sen. John McCain

Reporter: Aviva Lev-Ari, PhD, RN

We wish all patients diagnosed with Glioblastoma to be able to benefit from the advancements in Sciences reported, below

SOURCE

Glioblastoma Is A Grim Diagnosis, But There Are Some Signs Of Hope

Karen Weintraub, July 20, 2017 Updated July 21, 2017 5:33 PM

 

Advancements in Crossing The Blood-Brain Barrier

Paula Hammond, of MIT’s Koch Institute of Integrative Cancer Research: “We believe we have a handle on a good stealth mechanism. Now, we’re looking at enhanced uptake,” she said. “We have to begin to think a little bit about how to get nature on our side on this one.”

At the Brigham, researchers are trying another approach to getting across the blood-brain-barrier: prying open holes in its armor with beams of ultrasound. Although normally used to take cool pictures during pregnancy, multiple beams of ultrasound aimed at the same area can make blood vessels of the brain “leakier,” according to research at the Brigham.

 

Advancement in Stem Cells against Tumors

There’s also a possibility that stem cells may be useful for tracking down and killing tumor cells. Khalid Shah, director for the Center for Stem Cell Therapeutics and Imaging at Brigham and Women’s Hospital, has been experimenting with delivering engineered stem cells directly to tumor sites after surgery.

William Curry at Mass. General, is that the longer a patient with glioblastoma can hang on, the better their chances of getting one of these new treatments.

“The longer you stay alive and the longer you maintain good neurological function, the more eligible you one may be to see the benefits and the fruits of a lot of the research that is really accelerating right now,” he said.

SOURCE

Glioblastoma Is A Grim Diagnosis, But There Are Some Signs Of Hope

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Reporter and Curator: Irina Robu, PhD

Monitoring cancer patients and evaluating their response to treatment can sometimes involve invasive procedures, including surgery.

The liquid biopsies have become something of a Holy Grail in cancer treatment among physicians, researchers and companies gambling big on the technology. Liquid biopsies, unlike traditional biopsies involving invasive surgery — rely on an ordinary blood draw. Developments in sequencing the human genome, permitting researchers to detect genetic mutations of cancers, have made the tests conceivable. Some 38 companies in the US alone are working on liquid biopsies by trying to analyze blood for fragments of DNA shed by dying tumor cells.

Premature research on the liquid biopsy has concentrated profoundly on patients with later-stage cancers who have suffered treatments, including chemotherapy, radiation, surgery, immunotherapy or drugs that target molecules involved in the growth, progression and spread of cancer. For cancer patients undergoing treatment, liquid biopsies could spare them some of the painful, expensive and risky tissue tumor biopsies and reduce reliance on CT scans. The tests can rapidly evaluate the efficacy of surgery or other treatment, while old-style biopsies and CT scans can still remain inconclusive as a result of scar tissue near the tumor site.

As recently as a few years ago, the liquid biopsies were hardly used except in research. At the moment, thousands of the tests are being used in clinical practices in the United States and abroad, including at the M.D. Anderson Cancer Center in Houston; the University of California, San Diego; the University of California, San Francisco; the Duke Cancer Institute and several other cancer centers.

With patients for whom physicians cannot get a tissue biopsy, the liquid biopsy could prove a safe and effective alternative that could help determine whether treatment is helping eradicate the cancer. A startup, Miroculus developed a cheap, open source device that can test blood for several types of cancer at once. The platform, called Miriam finds cancer by extracting RNA from blood and spreading it across plates that look at specific type of mRNA. The technology is then hooked up at a smartphone which sends the information to an online database and compares the microRNA found in the patient’s blood to known patterns indicating different type of cancers in the early stage and can reduce unnecessary cancer screenings.

Nevertheless, experts warn that more studies are essential to regulate the accuracy of the test, exactly which cancers it can detect, at what stages and whether it improves care or survival rates.

SOURCE

https://www.fastcompany.com/3037117/a-new-device-can-detect-multiple-types-of-cancer-with-a-single-blood-test

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4356857/

Other related articles published in this Open Access Online Scientific Publishing Journal include the following:

Liquid Biopsy Chip detects an array of metastatic cancer cell markers in blood – R&D @Worcester Polytechnic Institute, Micro and Nanotechnology Lab

Reporters: Tilda Barliya, PhD and Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2016/12/28/liquid-biopsy-chip-detects-an-array-of-metastatic-cancer-cell-markers-in-blood-rd-worcester-polytechnic-institute-micro-and-nanotechnology-lab/

Liquid Biopsy Assay May Predict Drug Resistance

Curator: Larry H. Bernstein, MD, FCAP

https://pharmaceuticalintelligence.com/2015/11/06/liquid-biopsy-assay-may-predict-drug-resistance/

One blood sample can be tested for a comprehensive array of cancer cell biomarkers: R&D at WPI

Curator: Marzan Khan, B.Sc

https://pharmaceuticalintelligence.com/2017/01/05/one-blood-sample-can-be-tested-for-a-comprehensive-array-of-cancer-cell-biomarkers-rd-wpi

 

 

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Personalized Medicine been Positively affected by FDA Drug Approval Record

Reporter: Aviva Lev-Ari, PhD, RN

FDA to Clear Path for Drugs Aimed at Cancer-Causing Genes

By Anna Edney and Michelle Cortez

June 20, 2017, 10:41 AM EDT June 20, 2017, 3:02 PM EDT

https://www.bloomberg.com/news/articles/2017-06-20/fda-moves-to-clear-path-for-drugs-aimed-at-cancer-causing-genes

 

 

‘Landmark FDA approval bolsters personalized medicine’

PMC – An Op-Ed in STAT News

by Edward Abrahams

June 21, 2017

Our understanding of cancer has been morphing from a tissue-specific disease — think lung cancer or breast cancer — to a disease characterized more by specific genes or biomarkers than by location. A recent FDA decision underscores that transition and further opens the door to personalized medicine.

Two years ago, the director of the FDA’s Office of Hematology and Oncology Products told the Associated Press that there was no precedent for the agency to approve a drug aimed at treating tumors that generate a specific biomarker no matter where the cancer is in the body. Such a drug had long been seen as the epitome of personalized medicine. But with the rapid pace of progress in the field, director Dr. Richard Pazdur said, such an approval could one day be possible.

That day has arrived.

In a milestone decision for personalized medicine, the FDA approved Merck’s pembrolizumab (Keytruda) late last month for the treatment of tumors that express one of two biomarkers regardless of where in the body the tumors are located. The decision marks the first time FDA has approved a cancer drug for an indication based on the expression of specific biomarkers rather than the tumor’s location in the body.

Keytruda is designed to help the immune system recognize and destroy cancer cells by targeting a specific cellular pathway. The FDA notes that the two biomarkers — microsatellite instability-high (MSI-H) and mismatch repair deficient (dMMR) — affect the proper repair of DNA inside cells.

The approval represents an important first for the field of personalized medicine, which anticipates an era in which physicians use molecular tests to classify different forms of cancer based on the biomarkers they express, then choose the right treatment for it. In contrast to standard cancer treatments, which are given to large populations of patients even though only a fraction of them will benefit, Keytruda was approved only for the 4 percent of cancer patients whose tumors exhibit MSI-H or dMMR mutations. That may help the health system save money by focusing resources only on patients who are likely to benefit from Keytruda.

Such “personalized” strategies now dominate the landscape for cancer drug development. Personalized medicines account for nearly 1 of every 4 FDA approvals from 2014 to 2016, and the Tufts Center for the Study of Drug Development estimates that more than 70 percent of cancer drugs now in development are personalized medicines.

While this is encouraging, the U.S. research, regulatory, and reimbursement systems aren’t aligned to stimulate the development of personalized medicines, and may even deter progress.

The Trump administration’s proposal to cut biomedical research spending at the National Institutes of Health by 18 percent in fiscal year 2018, for example, would undermine its ability to fund more studies like the National Cancer Institute’s Molecular Analysis for Therapy Choice (MATCH) trial, which is designed to test targeted therapies across tumor types.

While the regulatory landscape for these targeted medicines is clear, the path to market for the molecular tests that do the targeting is not. That uncertainty continues to stifle investment in the innovative tests that make personalized medicine possible. The result is a clinical environment in which the patients who could benefit from personalized medicines are often never identified because the necessary tests aren’t available to them.

Finally, increasing pressure on pharmaceutical and diagnostic companies to decrease prices without considering their value to individual patients and the health system could also deter investment in innovative solutions that address unmet medical needs, particularly for smaller patient populations.

Confronted with unprecedented opportunities in personalized medicine, policymakers would do well to ensure that our research, regulatory, and reimbursement systems facilitate the development of and access to these promising new therapies. Only then can we ensure that Keytruda’s groundbreaking approval represents the beginning of a new era that promises better health and a more cost-effective health system.

Edward Abrahams, Ph.D., is president of the Personalized Medicine Coalition.

 

 

 

SOURCE

From: <cwells@personalizedmedicinecoalition.org>

Date: Wednesday, June 21, 2017 at 1:38 PM

To: Aviva Lev-Ari <AvivaLev-Ari@alum.berkeley.edu>

Subject: PMC in STAT: “Landmark FDA Approval Bolsters Personalized Medicine”

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City of Hope, Duarte, California – Combining Science with Soul to Create Miracles at a Comprehensive Cancer Center designated by the National Cancer InstituteAn Interview with the Provost and Chief Scientific Officer of City of Hope, Steven T. Rosen, M.D.

Author: Gail S. Thornton, M.A.

Co-Editor: The VOICES of Patients, Hospital CEOs, HealthCare Providers, Caregivers and Families: Personal Experience with Critical Care and Invasive Medical Procedures

 

City of Hope (https://www.cityofhope.org/homepage), a world leader in the research and treatment of cancer, diabetes, and other serious diseases, is an independent, biomedical research institution and comprehensive cancer center committed to researching, treating and preventing cancer, with an equal commitment to curing and preventing diabetes and other life-threatening diseases. Founded in 1913, City of Hope is one of only 47 comprehensive cancer centers in the nation, as designated by the National Cancer Institute.

City of Hope possesses flexibility that larger institutions typically lack. Innovative concepts move quickly from the laboratory to patient trials — and then to market, where they benefit patients around the world.

As a founding member of the National Comprehensive Cancer Network, their research and treatment protocols advance care throughout the nation. They are also part of ORIEN (Oncology Research Information Exchange Network), the world’s largest cancer research collaboration devoted to precision medicine. And they continue to receive the highest level of accreditation by the American College of Surgeons Commission on Cancer for their exceptional level of cancer care.

As an innovator, City of Hope is a pioneer in bone marrow and stem cell transplants with one of the largest and most successful of its kind in the world. Other examples of its leadership and innovation include,

  • Numerous breakthrough cancer drugs, including Herceptin, Rituxan, Erbitux, and Avastin, are based on technology pioneered by City of Hope and are saving lives worldwide.
  • To date, City of Hope surgeons have performed more than 10,000 robotic procedures for prostate, kidney, colon, liver, bladder, gynecologic, oral and other cancers.
  • They are a national leader in islet cell transplantation, which has the potential to reverse type 1 diabetes, and also provide islet cells for research at other institutions throughout the U.S.
  • Millions of people with diabetes benefit from synthetic human insulin, developed through research conducted at City of Hope.
  • Their scientists are pioneering the application of blood stem cell transplants to treat patients with HIV- and AIDS related lymphoma. Using a new form of gene therapy, their researchers achieved the first long-term persistence of anti-HIV genes in patients with AIDS-related lymphoma — a treatment that may ultimately cure lymphoma and HIV/AIDS.

 

Additionally, City of Hope has three on-campus manufacturing facilities producing biologic and chemical compounds to good manufacturing practice (GMP) standards.

City of Hope launched its Alpha Clinic, thanks to an $8 million, five-year grant from the California Institute for Regenerative Medicine (CIRM). The award is part of CIRM’s Alpha Stem Cell Clinics program, which aims to create one-stop centers for clinical trials focused on stem cell treatments for currently incurable diseases. The Alpha Clinics Network is already running 35 different clinical trials involving hundreds of patients, 17 of which are being conducted at City of Hope. Current clinical trials include transplants of blood stem cells modified to treat patients with AIDS and lymphoma, neural stem cells to deliver drugs directly to cancers hiding in the brain, and T cell immunotherapy trials.

Located just northeast of Los Angeles, landscaped gardens and open spaces surround City of Hope’s leading-edge medical and research facilities at its main campus in Duarte, California. City of Hope also has 14 community practice clinics throughout Southern California.

COH robotic (1)COH Helford H (1)COH1 Dr__Rosen_Clinic-2 (2)COH8 Janice_Huss-7COH7 COH_1369COH6 GMP_0454COH4 DSC_9279

Image SOURCE: Photographs courtesy of City of Hope, Duarte, California. Interior and exterior photos of the City of Hope, including Dr. Steven T. Rosen and his team.

 

Below is my interview with the Provost and Chief Scientific Officer of City of Hope, Steven T. Rosen, M.D., which occurred in April, 2017.

 

What sets City of Hope apart from other hospitals and research centers?

Dr. Rosen: City of Hope offers a unique blend of compassionate care and research innovation that simply can’t be found anywhere else.

We’re more than a medical center, and more than a research facility. We take the most compassionate patient-focused care available, combine it with today’s leading-edge medical advances, and infuse both with a quest to deliver better outcomes.

I’m proud to say that we’re known for rapidly translating scientific research into new treatments and cures, and that our technology has led to the development of four of the most widely used cancer-fighting drugs, Herceptin (trastuzumab), Avastin (bevacizumab), Erbitux (cetuximab), and Rituxin (rituximab).

City of Hope is a family. Our special team of experts treats the whole person and the family, not just a body, or a case or a disease. In fact, some of our patients have shared their stories of success. It is gratifying for me and our many health professionals to be able to make a positive difference in their lives.

Eleven years ago, Los Angeles firefighter Gus Perez was facing a battle far greater than any he’d ever known. He was diagnosed with CML (chronic myelogenous leukemia). Gus began receiving the drug Gleevec, which put him into remission. Given the drug’s success, he almost resigned himself to staying on it, yet was drawn to another option: undergoing a bone marrow transplant at City of Hope. “I went to my favorite ocean spot,” Gus recalls. “I put on my wetsuit, like I’ve done thousands of times, and paddled out. Every wave was special because I wasn’t sure if I was ever going to be back. And I remember getting out of the water and counting the steps to my car, thinking, ‘I’m going to beat this. I’m going to retrace those steps.’ And I’m happy to say I was able to do it.” Gus and his family recently celebrated the 10th anniversary of his bone marrow transplant. “City of Hope is more than just medical treatment,” Gus says. “They have to put you back together from the ground up. And to me, that’s truly a miracle.”

 

As an active 14-year-old, Nicole Schulz loved cheerleading and hanging out with her friends. Then her whole world changed. Nicole learned that her fatigue and other symptoms weren’t “just the flu,” but the effects of acute myelogenous leukemia (AML), an aggressive disease that rendered her bone marrow 97 percent cancerous. Nicole spent the next three and a half months at City of Hope, fighting the cancer with a daily regimen of chemotherapy and blood and platelet transfusions. “It put me into remission,” Nicole says. “But I wasn’t cured. And I wanted a cure.” Fortunately, Nicole was a candidate for a bone marrow transplant. Her malfunctioning marrow cells would be replaced with healthy marrow from a matching unrelated donor. “I never gave up — and neither did City of Hope,” Nicole says. After two bone marrow transplants and tremendous perseverance, Nicole is back to living the life she once knew and quickly making up for lost time.

 

When Jim Murphy’s doctor called and asked to see him on Christmas Eve, Jim knew it wasn’t going to be good news. And he was right. “The diagnosis was esophageal cancer,” Jim says. “Once they tell you that, there’s nothing you can do but formulate your action plan.” Jim would need to undergo chemotherapy, radiation and surgery to remove the tumor from his esophagus. It would require taking two-thirds of his esophagus and a third of his stomach. Despite the intense treatment, Jim was determined to keep his life as normal as possible. Throughout his chemotherapy and radiation therapy, he never missed a day of work, even riding his mountain bike to and from City of Hope to take his treatments. “I needed to show myself one victory after another,” Jim says. “I know City of Hope appreciated the fact that I was fighting as hard as they were.” Now cancer-free for several years, Jim credits City of Hope with giving him the best chance to fight his disease. “What really impressed me was that the research was right there at City of Hope. If they have something experimental, it goes from the researcher, right to the doctor and right to you. It’s the ultimate weapon — doctors reaching out for researchers, researchers reaching out for doctors. And the patient wins.”

 

City of Hope is a pioneer in the fields of bone marrow transplantation, diabetes and breakthrough cancer drugs based on technology developed at the institution.  How are you transforming the future of health care by turning science into a practical benefit for patients? 

Dr. Rosen: This is a distinctive place where brilliant research moves rapidly from concept to cure. That’s what we do—we speed breakthroughs in the lab to benefit patients in the clinic

Many know us for our leadership in fighting cancer, but fighting cancer is only part of our story. For decades, we’ve been making history in the fight against diabetes and other life-threatening illnesses that can be just as dangerous, and shattering, to patients and their families.

Every year, we conduct 400+ clinical trials, enrolling 6,000+ patients; hold 300+ patents and submit nearly 30 applications to the U.S. Food and Drug Administration (FDA) for investigational new drugs; and offer comprehensive assistance for patients and their families, including patient education, support groups, social resources, mind-body therapies and patient navigators.

We also translate breakthrough laboratory findings into real, lifesaving treatments and cures, and manufacture them at three on-campus facilities. Our goal is to get patients the treatments they need as fast as humanly possible.

We are in the race to save lives – and win. In our research efforts, we are teaching immune cells to attack tumors and Don J. Diamond [Ph.D.], Vincent Chung, [M.D.], and other City of Hope researchers launched a clinical trial seeking ways to effectively activate a patient’s own immune system to fight his or her cancer. The team is combining an immune-boosting vaccine with a drug that inhibits tumor cells’ ability to grow — to encourage immune cells to attack and eliminate tumors such as non-small cell lung cancer, melanoma, triple-negative breast cancer, renal cell carcinoma and many other cancer types.

City of Hope’s Diabetes & Metabolism Research Institute is committed to developing a cure for type 1 diabetes (T1D) within six years, fueled by a $50 million funding program led by the Wanek family. Research is already underway to unlock the immune system’s role in diabetes, including T cell modulation and stem cell-based therapies that may reverse the autoimmune attack on islet cells in the pancreas, which is the cause of T1D. City of Hope’s Bart Roep [Ph.D.], previously worked at Leiden University Medical Center in the Netherlands, where he was instrumental in launching a phase 1 clinical trial for a vaccine that aims to spur the immune system to fight, and possibly cure, T1D. Plans are developing for a larger, phase 2 trial to launch in the future at City of Hope.

 

What makes your recent alliance with Translational Genomics Research Institute (TGen) different from other efforts in precision medicine around the country and within our Government to identify treatments for cancer?

Dr. Rosen: Precision medicine is the future of cancer care. Since former Vice President’s Joe Biden’s Moonshot Cancer program was launched to achieve 10 years of progress in preventing, diagnosing and treating cancer, within five years, federal cancer funding has been prioritized to address these aims.

City of Hope and the Translational Genomics Research Institute (TGen) have formed an alliance to fast-track the future of precision medicine for patients. Our clinical leadership as a comprehensive cancer center combined with TGen’s leadership in molecular cancer research will propel us to the forefront of precision medicine and is further evidence of our momentum in transforming the future of health.

In fact, most recently scientists at TGen have identified a potent compound in the fight for an improved treatment against glioblastoma multiforme (GBM), the most common and deadly type of adult brain cancer. This research could represent a breakthrough for us to find an effective long-term treatment. The compound prevents glioblastoma from spreading, and leaves cancer vulnerable to chemotherapy and radiation.  Aurintricarboxylic Acid (ATA) is a chemical compound that in laboratory tests was shown to block the chemical cascade that otherwise allows glioblastoma cells to invade normal brain tissue and resist both chemo and radiation therapy.

The goal is to accelerate the speed at which we advance research discoveries into the clinic to benefit patients worldwide.

 

As a prestigious Comprehensive Cancer Center, City of Hope was named this year as one of the top 20 cancer centers for the past 10 years. How do you achieve that designation year after year? And what specific collaborations, clinical trials and multidisciplinary research programs are under way that offer benefits to patients?

Dr. Rosen: It’s simple – we achieve this through the compassion, commitment and excellence of the City of Hope family, which includes our world-class physicians, staff, supporters and donors.

We look to find the best and brightest professionals and bring them to City of Hope to work with our amazing staff on research, treatments and cures that not only change people’s lives, but also change the world.

We also have a community of forward-looking, incredibly generous and deeply committed supporters and donors. People who get it. People who share our vision. People who take their capacity for business success and apply it to helping others. They provide the fuel that drives us forward, enabling us to do great things.

City of Hope has a long track record of research breakthroughs and is constantly working to turn novel scientific research into the most advanced medical services.

Right now, we have a number of collaborative programs underway, including: Our alliance with TGen to make precision medicine a reality for patients, The Wanek Family Project to Cure Type 1 Diabetes, and Immunotherapy and CAR-T cell therapy clinical trials, which aim to fight against brain tumors and blood cancers.

More specifically, our research team led by Hua Yu, [Ph.D.] and Andreas Herrmann, [Ph.D.], developed a drug to address the way in which cancer uses the STAT3 protein to “corrupt” the immune system. The drug, CpG-STAT3 siRNA, halts the protein’s ability to “talk” to the immune system. It blocks cancer cell growth while sending a message to surrounding immune cells to destroy a tumor, and it may also enhance the effectiveness of other immunotherapies, such as T-cell therapy.

We could also see a functional cure for HIV in the next 5 to 10 years. Gene therapy pioneer, John A. Zaia, [M.D.], the Aaron D. Miller and Edith Miller Chair in Gene Therapy, the director of the Center for Gene Therapy within City of Hope’s Hematologic Malignancies and Stem Cell Transplantation Institute, as well as principal director of our Alpha Clinic, and researchers are building on knowledge gained from the case of the so-called “Berlin patient” whose HIV infection vanished after receiving a stem cell transplant for treatment of leukemia. The donor’s CCR5 gene, HIV’s typical pathway into the body, had a mutation that blocked the virus. The team launched a clinical trial that used a zinc finger nuclease to “cut out” the CCR5 gene, leaving HIV with no place to go. Their goal: to someday deliver a one-time treatment that produces a lifetime change. Integral to the first-in-human trials are the nurses who understand the study protocols, potential side effects and symptoms.

 

Would you share some of the current science under way on breakthrough cures for cancer?

Dr. Rosen: We are achieving promising results in many innovative approaches – gene therapy, targeted therapy, immunotherapy and all aspects of precision medicine. We are also forging new partnerships and collaboration agreements around the world.

Let me share with you a few examples of our cutting-edge science.

City of Hope researchers identified a promising new strategy for dealing with PDAC, an aggressive form of pancreatic cancer. The bacterial-based therapy homes to tumors and provokes an extremely effective tumor-killing response.

Teams at City of Hope are working to load nanoparticles with small snippets of DNA molecules that can stimulate the immune system to attack tumor cells in the brain. This innovative approach can overcome the blood-brain barrier, which blocks many drugs from reaching the tumor site.

A pioneer in islet cell transplantation for the treatment of diabetes, City of Hope conducted a clinical trial to refine its transplantation protocol. Because this new protocol includes an ATG (antithymoglobulin) induction, the immune system will not harm the transplant. The immune-suppression strategy used in the trial is considered a significant improvement over the protocol used in previous islet cell transplant trials.

City of Hope physicians and scientists joined a multinational team in reporting the success of a phase II clinical trial of a novel drug against essential thrombocythemia (ET). ET patients make too many platelets (cells essential for blood clotting), which puts them at risk for abnormal clotting and bleeding. All 18 patients treated with the drug, imetelstat, exhibited decreased platelet levels, and 16 showed normalized blood cell counts.

Researchers found that the CMVPepVax vaccine — developed at City of Hope to boost cellular immunity against cytomegalovirus (CMV) — is safe and effective in stem cell transplant recipients. Building on this discovery, City of Hope and Fortress Biotech formed a company to develop two vaccines, PepVax and Triplex, against CMV, a life-threatening illness in people who have weakened or underdeveloped immune systems such as cancer patients and developing fetuses. The vaccines are the subjects of multisite clinical trials. These City of Hope vaccines could open the door to a new way of protecting cancer patients from CMV, a devastating infection that affects hundreds of thousands of people worldwide.

 

In what ways does the initial vision of Samuel H. Golter impact the work you are doing today? What does the tagline – “The Miracle of Science with Soul” – mean?

Dr. Rosen: 100+ years ago, Samuel Golter, one of the founders of City of Hope said: “There is no profit in curing the body if in the process we destroy the soul.” For decades, City of Hope has lived by this credo, providing a comprehensive, compassionate and research-based treatment approach.

“The Miracle of Science with Soul” refers to the lives that we save by uniting science and research with compassionate care.

“Miracle” represents what people with cancer and other deadly diseases say they want most of all.

“Science” speaks to the many innovations we’ve pioneered, which demonstrate that medical miracles happen here.

“Soul” represents our compassionate care. We’re an untraditional health system — and our people, culture and campus reflect this.

 

Can you please describe how City of Hope has evolved throughout its 100-year history from a tuberculosis sanitorium into a world-class research-centered institution? 

Dr. Rosen: City of Hope is a leading comprehensive cancer center and independent biomedical research institution. Over the years, our discoveries have changed the lives of millions of patients around the world.

We pioneered the research leading to the first synthetic insulin and the technology behind numerous cancer-fighting drugs, including Herceptin (trastuzumab), Avasatin (bevacizumab), Erbitux (cetuximab), and Rituxin (rituximab).

As previously mentioned, we hold 300+ patents, have numerous potential therapies in the pipeline at any given time, and treat 1,000+ patients a year in therapeutic clinical trials.

These numbers reflect our commitment to innovation and rapid translation of science into therapies to benefit patients.

We are home to Beckman Research Institute of City of Hope, the first of only five Beckman Research Institutes established by funding from the Arnold and Mabel Beckman Foundation. It is responsible for fundamentally expanding the world’s understanding of how biology affects diseases such as cancer, HIV/AIDS and diabetes.

Recognizing our team’s accomplishments in cancer research, treatment, patient care, education and prevention, the National Cancer Institute has designated City of Hope as a comprehensive cancer center. This is an honor reserved for only 47 institutions nationwide. Our five Cancer Center Research Programs run the gamut from basic and translational studies, to Phase I and II clinical protocols and follow-up studies in survivorship and symptom management.

City of Hope’s Diabetes & Metabolism Research Institute offers a broad diabetes and endocrinology program combining groundbreaking research, unique treatments and comprehensive education to help people with diabetes and other endocrine diseases live longer, better lives.

Our dedicated, multidisciplinary team of healthcare professionals at the Hematologic Malignancies & Stem Cell Institute combine innovative research discoveries with superior clinical treatments to improve outcomes for patients with hematologic cancers.

Working closely with the City of Hope comprehensive cancer center’s Developmental Cancer Therapeutics Program and other cancer centers, the Medical Oncology & Therapeutics Research multidisciplinary program includes basic, translational and clinical research and fosters collaborations among scientists and clinicians.

City of Hope’s Radiation Oncology Department is on the forefront of improving patient care, and our staff is constantly studying new research technologies, clinical trials and treatment methods that can lead to better outcomes and quality of life for our patients.

What attracted you to City of Hope? And how do you define success in your present role as provost and CSO?

Dr. Rosen: Helping cancer patients and their families gives me a sense of purpose. I encourage everyone to find a passion and find an organization that fits their passion. City of Hope is a special place. What we do is bigger than ourselves.

I define success as finding cures and helping patients live stronger, better lives. I am focused on leading a diverse team of scientists, clinicians and administrative leaders committed to discovering breakthroughs and specialized therapies.

COH2 Dr__Steve_Rosen_

Image SOURCE: Photograph of Provost and Chief Scientific Officer Steven T. Rosen, M.D., courtesy of City of Hope, Duarte, California.

 

Steven T. Rosen, M.D.
Provost and Chief Scientific Officer

City of Hope
Duarte, California

Steven T. Rosen, M.D., is provost and chief scientific officer for City of Hope and a member of City of Hope’s Executive Team. He also is director of the Comprehensive Cancer Center and holds the Irell & Manella Cancer Center Director’s Distinguished Chair, and he is director of Beckman Research Institute (BRI) and the Irell & Manella Graduate School of Biological Sciences.

Dr. Rosen sets the scientific direction of City of Hope, shaping the research and educational vision for the biomedical research, treatment and education institution. Working closely and collaboratively with City of Hope’s scientists, clinicians and administrative leaders, he develops strategies that contribute to the organization’s mission.

As director of BRI, he works with faculty across the institution to help shape and direct the scientific vision for BRI while leading the vital basic and translational research that is fundamental to our strategic plan and mission. He focuses on opportunities for expanding and integrating our research initiatives; recruiting and leading talented scientists; helping our talented researchers achieve national and international recognition; and promoting our national standing as a premier scientific organization.

Prior to joining City of Hope, Dr. Rosen was the Genevieve Teuton Professor of Medicine at the Feinberg School of Medicine at Northwestern University in Chicago. He served for 24 years as director of Northwestern’s Robert H. Lurie Comprehensive Cancer Center. Under his leadership, the center received continuous National Cancer Institute (NCI) funding beginning in 1993 and built nationally recognized programs in laboratory sciences, clinical investigations, translational research and cancer prevention and control. The center attained comprehensive status in 1997.

Dr. Rosen has published more than 400 original reports, editorials, books and book chapters. His research has been funded by the National Cancer Institute, American Cancer Society, Leukemia & Lymphoma Society of America and Multiple Myeloma Research Foundation.

Dr. Rosen also has served as an adviser for several of these organizations and on the external advisory boards of more than a dozen NCI-designated Comprehensive Cancer Centers. He is the current editor-in-chief of the textbook series “Cancer Treatment & Research.”

Recognized as one of the Best Doctors in America, Dr. Rosen is a recipient of the Martin Luther King Humanitarian Award from Northwestern Memorial Hospital and the Man of Distinction Award from the Israel Cancer Research Fund. He earned his bachelor’s degree and medical degree with distinction from Northwestern University from which he also earned the Alumni Merit Award, and is a member of the Alpha Omega Alpha Honor Society.

Editor’s Note: 

We would like to thank Mary-Fran Faraji, David Caouette, and Chantal Roshetar of the Communications and Public Affairs department at the City of Hope, for the gracious help and invaluable support they provided during this interview.

 

REFERENCE/SOURCE

The City of Hope (https://www.cityofhope.org/homepage), Duarte, California.

Other related articles

Retrieved from https://www.cityofhope.org/people/rosen-steven

Retrieved from https://www.cityofhope.org/research/beckman-research-institute

Retrieved from https://www.cityofhope.org/research/comprehensive-cancer-center

Retrieved from https://www.cityofhope.org/research/research-overview/diabetes-metabolism-research-institute

Retrieved from https://www.cityofhope.org/patients/departments-and-services/hematologic-malignancies-and-stem-cell-transplantation-institute

Retrieved from https://www.cityofhope.org/patients/departments-and-services/medical-oncology-and-therapeutics-research/medical-oncology-research

Retrieved from https://www.cityofhope.org/patients/cancers-and-treatments/departments-and-services/radiation-oncology/radiation-oncology-research

                        

Other related articles were published in this Open Access Online Scientific Journal include the following: 

2017

Expedite Use of Agents in Clinical Trials: New Drug Formulary Created – The NCI Formulary is a public-private partnership between NCI, part of the National Institutes of Health, and pharmaceutical and biotechnology companies

https://pharmaceuticalintelligence.com/2017/01/12/expedite-use-of-agents-in-clinical-trials-new-drug-formulary-created-the-nci-formulary-is-a-public-private-partnership-between-nci-part-of-the-national-institutes-of-health-and-pharmaceutical-and/

The top 15 best-selling cancer drugs in 2022 & Projected Sales in 2020 of World’s Top Ten Oncology Drugs

https://pharmaceuticalintelligence.com/2017/01/03/projected-sales-in-2020-of-worlds-top-ten-oncology-drugs/

2016

Funding Opportunities for Cancer Research

https://pharmaceuticalintelligence.com/2016/12/08/funding-opportunities-for-cancer-research/

Recent Breakthroughs in Cancer Research at the Technion-Israel Institute of Technology- 2015

https://pharmaceuticalintelligence.com/2016/02/03/recent-breakthroughs-in-cancer-research-at-the-technion-israel-institute-of-technology-2015/

New York Times Articles on Cancer Immunotherapy and Cancer Treatment Options

https://pharmaceuticalintelligence.com/2016/08/09/new-york-times-articles-on-immunotherapy-and-cancer-treatment-options/

  • Cancer Biology & Genomics for Disease Diagnosis, on Amazon since 8/11/2015

http://www.amazon.com/dp/B013RVYR2K

https://pharmaceuticalintelligence.com/biomed-e-books/series-c-e-books-on-cancer-oncology/volume-2-immunotherapy-in-oncology/

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