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Archive for the ‘Precision Cancer Medicine’ Category


37th Annual J.P. Morgan HEALTHCARE CONFERENCE: News at #JPM2019 for Jan. 10, 2019: Deals and Announcements

Reporter: Stephen J. Williams, Ph.D.

From Biospace.com

 

JP Morgan Healthcare Conference Update: Sage, Mersana, Shutdown Woes and Babies

Speaker presenting to audience at a conference

With the J.P. Morgan Healthcare Conference winding down, companies remain busy striking deals and informing investors about pipeline advances. BioSpace snagged some of the interesting news bits to come out of the conference from Wednesday.

SAGE Therapeutics – Following a positive Phase III report that its postpartum depression treatment candidate SAGE-217 hit the mark in its late-stage clinical trial, Sage Therapeutics is eying the potential to have multiple treatment options available for patients. At the start of J.P. Morgan, Sage said that patients treated with SAGE-217 had a statistically significant improvement of 17.8 points in the Hamilton Rating Scale for Depression, compared to 13.6 for placebo. The company plans to seek approval for SAGE-2017, but before that, the FDA is expected to make a decision on Zulresso in March. Zulresso already passed muster from advisory committees in November, and if approved, would be the first drug specifically for postpartum depression. In an interview with the Business Journal, Chief Business Officer Mike Cloonan said the company believes there is room in the market for both medications, particularly since the medications address different patient populations.

 

Mersana Therapeutics – After a breakup with Takeda Pharmaceutical and the shelving of its lead product, Cambridge, Mass.-based Mersana is making a new path. Even though a partial clinical hold was lifted following the death of a patient the company opted to shelve development of XMT-1522. During a presentation at JPM, CEO Anna Protopapas noted that many other companies are developing therapies that target the HER2 protein, which led to the decision, according to the Boston Business Journal. Protopapas said the HER2 space is highly competitive and now the company will focus on its other asset, XMT-1536, an ADC targeting NaPi2b, an antigen highly expressed in the majority of non-squamous NSCLC and epithelial ovarian cancer. XMT-1536 is currently in Phase 1 clinical trials for NaPi2b-expressing cancers, including ovarian cancer, non-small cell lung cancer and other cancers. Data on XMT-1536 is expected in the first half of 2019.

Novavax – During a JPM presentation, Stan Erck, CEO of Novavax, pointed to the company’s RSV vaccine, which is in late-stage development. The vaccine is being developed for the mother, in order to protect an infant. The mother transfers the antibodies to the infant, which will provide the baby with protection from RSV in its first six months. Erck called the program historic. He said the Phase III program is in its fourth year and the company has vaccinated 4,636 women. He said they are tracking the women and the babies. Researchers call the mothers every week through the first six months of the baby’s life to acquire data. Erck said the company anticipates announcing trial data this quarter. If approved, Erck said the market for the vaccine could be a significant revenue driver.

“You have 3.9 million birth cohorts and we expect 80 percent to 90 percent of those mothers to be vaccinated as a pediatric vaccine and in the U.S. the market rate is somewhere between $750 million and a $1 billion and then double that for worldwide market. So it’s a large market and we will be first to market in this,” Erck said, according to a transcript of the presentation.

Denali Therapeutics – Denali forged a collaboration with Germany-based SIRION Biotech to develop gene therapies for central nervous disorders. The two companies plan to develop adeno-associated virus (AAV) vectors to enable therapeutics to cross the blood-brain barrier for clinical applications in neurodegenerative diseases including Parkinson’s, Alzheimer’s disease, ALS and certain other diseases of the CNS.

AstraZeneca – Pharma giant AstraZeneca reported that in 2019 net prices on average across the portfolio will decrease versus 2018. With a backdrop of intense public and government scrutiny over pricing, Market Access head Rick Suarez said the company is increasing its pricing transparency. Additionally, he said the company is looking at new ways to price drugs, such as value-based reimbursement agreements with payers, Pink Sheet reported.

Amarin Corporation – As the company eyes a potential label expansion approval for its cardiovascular disease treatment Vascepa, Amarin Corporation has been proactively hiring hundreds of sales reps. In the fourth quarter, the company hired 265 new sales reps, giving the company a sales team of more than 400, CEO John Thero said. Thero noted that is a label expansion is granted by the FDA, “revenues will increase at least 50 percent over what we did in the prior year, which would give us revenues of approximate $350 million in 2019.”

Government Woes – As the partial government shutdown in the United States continues into its third week, biotech leaders at JPM raised concern as the FDA’s carryover funds are dwindling. With no new funding coming in, reviews of New Drug Applications won’t be able to continue past February, Pink Sheet said. While reviews are currently ongoing, no New Drug Applications are being accepted by the FDA at this time. With the halt of NDA applications, that has also caused some companies to delay plans for an initial public offering. It’s hard to raise potential investor excitement without the regulatory support of a potential drug approval. During a panel discussion, Jonathan Leff, a partner at Deerfield Management, noted that the ongoing government shutdown is a reminder of how “overwhelmingly dependent the whole industry of biotech and drug development is on government,” Pink Sheet said.

Other posts on the JP Morgan 2019 Healthcare Conference on this Open Access Journal include:

#JPM19 Conference: Lilly Announces Agreement To Acquire Loxo Oncology

36th Annual J.P. Morgan HEALTHCARE CONFERENCE January 8 – 11, 2018

37th Annual J.P. Morgan HEALTHCARE CONFERENCE: #JPM2019 for Jan. 8, 2019; Opening Videos, Novartis expands Cell Therapies, January 7 – 10, 2019, Westin St. Francis Hotel | San Francisco, California

37th Annual J.P. Morgan HEALTHCARE CONFERENCE: News at #JPM2019 for Jan. 8, 2019: Deals and Announcements

 

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Role of Informatics in Precision Medicine: Notes from Boston Healthcare Webinar: Can It Drive the Next Cost Efficiencies in Oncology Care?

Reporter: Stephen J. Williams, Ph.D.

 

Boston Healthcare sponsored a Webinar recently entitled ” Role of Informatics in Precision Medicine: Implications for Innovators”.  The webinar focused on the different informatic needs along the Oncology Care value chain from drug discovery through clinicians, C-suite executives and payers. The presentation, by Joseph Ferrara and Mark Girardi, discussed the specific informatics needs and deficiencies experienced by all players in oncology care and how innovators in this space could create value. The final part of the webinar discussed artificial intelligence and the role in cancer informatics.

 

Below is the mp4 video and audio for this webinar.  Notes on each of the slides with a few representative slides are also given below:

Please click below for the mp4 of the webinar:

 

 


  • worldwide oncology related care to increase by 40% in 2020
  • big movement to participatory care: moving decision making to the patient. Need for information
  • cost components focused on clinical action
  • use informatics before clinical stage might add value to cost chain

 

 

 

 

Key unmet needs from perspectives of different players in oncology care where informatics may help in decision making

 

 

 

  1.   Needs of Clinicians

– informatic needs for clinical enrollment

– informatic needs for obtaining drug access/newer therapies

2.  Needs of C-suite/health system executives

– informatic needs to help focus of quality of care

– informatic needs to determine health outcomes/metrics

3.  Needs of Payers

– informatic needs to determine quality metrics and managing costs

– informatics needs to form guidelines

– informatics needs to determine if biomarkers are used consistently and properly

– population level data analytics

 

 

 

 

 

 

 

 

 

 

 

 

What are the kind of value innovations that tech entrepreneurs need to create in this space? Two areas/problems need to be solved.

  • innovations in data depth and breadth
  • need to aggregate information to inform intervention

Different players in value chains have different data needs

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Data Depth: Cumulative Understanding of disease

Data Depth: Cumulative number of oncology transactions

  • technology innovators rely on LEGACY businesses (those that already have technology) and these LEGACY businesses either have data breath or data depth BUT NOT BOTH; (IS THIS WHERE THE GREATEST VALUE CAN BE INNOVATED?)
  • NEED to provide ACTIONABLE as well as PHENOTYPIC/GENOTYPIC DATA
  • data depth more important in clinical setting as it drives solutions and cost effective interventions.  For example Foundation Medicine, who supplies genotypic/phenotypic data for patient samples supplies high data depth
  • technologies are moving to data support
  • evidence will need to be tied to umbrella value propositions
  • Informatic solutions will have to prove outcome benefit

 

 

 

 

 

How will Machine Learning be involved in the healthcare value chain?

  • increased emphasis on real time datasets – CONSTANT UPDATES NEED TO OCCUR. THIS IS NOT HAPPENING BUT VALUED BY MANY PLAYERS IN THIS SPACE
  • Interoperability of DATABASES Important!  Many Players in this space don’t understand the complexities integrating these datasets

Other Articles on this topic of healthcare informatics, value based oncology, and healthcare IT on this OPEN ACCESS JOURNAL include:

Centers for Medicare & Medicaid Services announced that the federal healthcare program will cover the costs of cancer gene tests that have been approved by the Food and Drug Administration

Broad Institute launches Merkin Institute for Transformative Technologies in Healthcare

HealthCare focused AI Startups from the 100 Companies Leading the Way in A.I. Globally

Paradoxical Findings in HealthCare Delivery and Outcomes: Economics in MEDICINE – Original Research by Anupam “Bapu” Jena, the Ruth L. Newhouse Associate Professor of Health Care Policy at HMS

Google & Digital Healthcare Technology

Can Blockchain Technology and Artificial Intelligence Cure What Ails Biomedical Research and Healthcare

The Future of Precision Cancer Medicine, Inaugural Symposium, MIT Center for Precision Cancer Medicine, December 13, 2018, 8AM-6PM, 50 Memorial Drive, Cambridge, MA

Live Conference Coverage @Medcity Converge 2018 Philadelphia: Oncology Value Based Care and Patient Management

2016 BioIT World: Track 5 – April 5 – 7, 2016 Bioinformatics Computational Resources and Tools to Turn Big Data into Smart Data

The Need for an Informatics Solution in Translational Medicine

 

 

 

 

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The Future of Precision Cancer Medicine, Inaugural Symposium, MIT Center for Precision Cancer Medicine, December 13, 2018, 8AM-6PM, 50 Memorial Drive, Cambridge, MA

Reporter: Aviva Lev-Ari, PhD, RN

#CPCM2018 @AVIVA1950 @pharma_BI

 

 

Aviva Lev-Ari, PhD, RN, Editor-in-Chief, will attend and cover this event in REAL TIME for

 http://pharmaceuticalintelligence.com 


Over the past decade, there have been major advancements in the field of precision medicine, leading to exciting new treatments for some cancer patients. Much attention has been focused on genomic profiling of tumors to identify genomic alterations that might guide selection of specific therapies for individual patients. Beyond genomics, however, there is a variety of other precision approaches that can identify and exploit cancer-specific biological mechanisms including proteomics, metabolomics, and computational modeling, resulting in the more effective use of existing cancer medicines. On Thursday, December 13, 2018, the MIT Center for Precision Cancer Medicine will hold its inaugural annual symposium in the Samberg Conference Center at MIT. This full-day event will feature leading researchers and clinicians, who will highlight recent advances in precision cancer medicine and share perspectives on the future. An industry panel will also discuss the barriers to instituting precision medicine into current and future clinical trials.

 


Keynote Address

Charles Sawyers

Charles Sawyers, MD

Chair, Human Oncology and Pathogenesis Program
Memorial Sloan Kettering Cancer Center

Speakers

Andrea Califano

Andrea Califano, PhD

Clyde and Helen Wu Professor of Chemical Systems Biology, Columbia University
Chair, Department of Systems Biology, Columbia University
Director, JP Sulzberger Columbia Genome Center
Associate Director, Herbert Irving Comprehensive Cancer Center

Chris Love

J. Christopher Love, PhD

Professor of Chemical Engineering, MIT
Associate Member, Ragon Institute of MGH, MIT and Harvard
Member, Koch Institute, MIT

Richard Marais

Richard Marais, PhD

Professor of Molecular Oncology
Director, CRUK Manchester Institute
The University of Manchester

Kenna Mills Shaw

Kenna Mills Shaw, PhD

Executive Director
Sheikh Khalifa Bin Zayed al Nahyan Institute for Personalized Cancer Therapy
MD Anderson Cancer Center

Alice Shaw

Alice Shaw, MD, PhD

Professor, Harvard Medical School
Director, Thoracic Cancer Program, Massachusetts General Hospital

Matt Vander Heiden

Matthew Vander Heiden, MD, PhD

Associate Professor of Biology, MIT
Associate Director, Koch Institute
Member, MIT Center for Precision Cancer Medicine

Mike Yaffe

Michael B. Yaffe, MD, PhD

David H. Koch Professor of Science, MIT
Professor of Biology and Biological Engineering, MIT
Director, MIT Center for Precision Cancer Medicine
Director, Koch Institute Clinical Investigator Program

Jean Zhao

Jean Zhao, PhD

Professor of Biological Chemistry and Molecular Pharmacology
Harvard Medical School and Dana-Farber Cancer Institute


Panelists: Barriers to Instituting Precision Medicine in Clinical Trials

Hammerman

Peter Hammerman, MD, PhD

Global Head, Translational Research
Oncology Disease Area
Novartis Institutes for BioMedical Research

Ho

Steffan N. Ho, MD, PhD

Vice President, Head of Translational Oncology
Pfizer Global Product Development

Shiva Malek

Shiva Malek, PhD

Director and Principal Scientist
Department of Discovery Oncology
Genentech Inc

Marks

Kevin Marks, PhD

VP of Biology
Agios Pharmaceuticals

Michael Rothenberg

S. Michael Rothenberg, MD, PhD

Vice-President, Research and Development
Loxo Oncology, Inc.

Angela Koehler

Moderator:

Angela Koehler, PhD

Goldblith Career Development Professor in Applied Biology, MIT
Member, Koch Institute for Integrative Cancer Research
Member, MIT Center for Precision Cancer Medicine

 

Speakers:

Panelists:

  • Peter Hammerman, Novartis Institutes for BioMedical Research
  • Steffan Ho, Pfizer
  • Shiva Malek, Genentech, Inc
  • Kevin Marks, Agios Pharmaceuticals
  • S. Michael Rothenberg, Loxo Oncology, Inc

Moderated by Angela Koehler, MIT’s Koch Institute

Agenda:

8:00 am Registration and continental breakfast

8:45 am Opening remarks by Michael Yaffe (MIT’s Koch Institute)

  • Season of great expectation, tumor genetics is just the beginning, beyond: science, engineering, medicine: beyond genomics: immunology, cell biology, early detection, new drug development for the undrugable, system biology, RNAi
  • Jack Tyler was the initiator to find a donor for CPCM

9:00 am Keynote Address by Charles L. Sawyers (Memorial Sloan Kettering Cancer Center)

  • developed a drug for prostate cancer
  • Clinical trained oncologist/genomics
  • Lineage Plasticity:
  1. luminal cells in histology of origin and basal cells and require androgen receptor AR) function
  2. deprive lunimal cells fro growth factor
  3. Hormonal therapy Leuprolite, degarelix [castration methastatic]
  4. after relapse 2nd generation anti-androgens abirateron
  5. PING MU ENZALUTAMIDE RESISTANCE P53/RB! DELETION CONFER
  6. TRANSCRIPTION CHANGE: ANTIADROGEN RESISTANCE
  7. Lineage shift Sox2 level goes up – prevent drug resistance, in vivo and in vitro
  8. SOX2 promotes lineage placticity and antiadrogen resistance in TP53 and RBI-deficient prostate cancer
  9. Evolution of Lineage plasticity over time
  10. AR Pathway inhibition accelerates lineage plasticity: synaptophysin-positive disease in-vivo
  11. scRNA-seq time course – modeled by diffusion map displayed in luminal and basal cells
  12. Emergence of EMT phenotype, with retention of epithelial features
  13. Use CRISPR to perturb luminal plasticity by phyeno type
  14. Genomic landscape of Primary Prostate Cancer: ERG gain drives luminal layer
  15. Different classes of FOXA1 mutations in Prostate organoid Cancer – Missense, inframe, truncated
  16. FOXA1 key in hormone receptor signaling
  17. Hypermorphic peaks – ATAC-seq neomorphic FOXA1 pioneering activity
  18. Common Prostate Cancer Genes:differentiation phenotypes: TP53 Loss, RB1 – Loss,
  19. work of Matan Hofree – four subtypes of luminal cells
  20. involution and regeneration of single cell RNAseq
  21. Transcriptional shifts in response to castration/androgen addback
  22. androgen addback: 50% of luminal cells are proliferation in 48 hours
  23. cell responsible for organ regeneration

 

9:45 am Alice T. Shaw (Massachusetts General Hospital)

  • evolution of drug resistance in Lung Cancer
  • oncogenic drivers in lung adenocarcenoma –
  1. EGFR – sensitizing 19.4% of all patients
  2. KRAS
  3. ALK
  4. ROS1
  5. CMET
  6. BRAF
  7. NTRK1
  8. RET

Delay and prevention of drug resistance: liquid biopsy of pleural fluids and serial blood collections

  • Crizotinib patient with ROS1 + nsclc
  • acquired mutation in ROS1 G2032R – resistance to Crizotinib – Michael Lawrence, MGH – analysis of mutation and resistance
  • Repotrectinib – for ROS1 – Resistance mediated by this mutation
  • If patient fails three antiinhibitor drugs: secondary ALK mutations mediate Crizotinib Resistance
  • 2nd generation of  ALK inhibitors are structurally Distinct molecules
  • Lorlatinib – 3rd generation –>> back to 1st generation Crizotinib
  • Clonal evolution of resistance in ALK in NSCLC
  • compound mutations in ALK mutations – Lorlatinib Resistance
  • Sequential TKI therapy foster the development of compound mutation refractory to all generations og ALK TKIs – compound mutation can’t be overcome
  • Intratumoral Heterogeneity revealed by multiregion sequencing of renal cell carcinoma and resected NSCLC
  • somatic mutations: Pre-treatment to Lorlatinib resistance
  • Clonal Analysis: Multiple Drivers of resistance underlie clinical relapse
  • genomic instability – eradicate residual disease to eliminate drug resistance and tolerance persistance

 

10:25 am Networking Break

10:45 am Richard Marais (Cancer Research UK, Manchester Institute)

  • Melanoma – Precision Medicin
  • Request – NOT TO PUBLISH on the INTERNET, some of the work presented is not PUBLISHED.
  • Request is honored

11:25 am Matthew Vander Heiden (MIT’s Koch Institute)

  • Targeting Metabolism is altered in cancer
  • Metabolism is glucose carbohydrates, lipids – conversion of nutrients into biomass: ATP, Protein, Nucleic acid,
  • Not -proliferating cells vs proliferating cells
  • genetic mutations, tissue of origin, lineage of cells — metabolism takes place: combination of these three facto
  • environment consists the metabolic network definers.d by cell intrinsic network
  • Assessment of nutrient levels in tumor microenvironment
  • Metabolite analysis: ion suppression vs nutrients
  • nutrients are available to cells in tumors
  • depletion of glucose vs enrichment
  • metabolite most different: Gluthamine, needed for cancer to grow
  • Lineage can contribute – tryptophane and argenine
  • gluthamine – Cyctine affect gluthamine sensitivity to gluthamine inhibitors
  • what you eat, where is the tumor locate, tissue environment — more important
  • therapeutic window: metabolism processes – cell proliferation
  • ability to make aspartate – given to mice pancreatic  — tumor grow faster
  • cellular oxidation state correlate with pyruvate oxidation — PDH Activator suppress oxidation
  • Aspartate vs NAD+/NADH – lactate TCA – form more carbon
  • PDH activation reduces Redux
  • Serine availability can limit proliferation even in cells with increase
  • Serine vs NAD regeneration
  • which cancer falls into which group : Serine pathway – increase serine synthesis: Melanoma vs Breast cancer
  • growth of breast cancer: Serine availability dependent – accelerate of inhibit growth by level of serine
  • Model for how nutrient limitation affect tumor growth, tumor size depends of serine levels

 

12:05 pm Box lunch

12:30 pm Industry panel: Barriers to instituting precision medicine into clinical trials

  • Long term benefits of Precision Medicine
  • What phynotype are now looked for?

Michael Rothenberg

  1. short term, identify mutations
  2. more testing is needed
  3. sequencing the therapies
  4. challenge getting tissue, doing experiments in house
  5. Industry needs Academia collaboration for accelerated innovations
  6. AI may lower the cost of drug discovery

KEVIN MARX:

  1. MECHANISM OF RESISTANCE – COMBINATORIAL DRUG DISCOVERY
  2. phynotyping, tissue acquisition immune phenotype, what drive therapeutic response?
  3. genetic drivers
  4. HR seeks Scientistist that worked in TEAMS, collaborative science

STEPHAN HO

  1. long term benefits are very important
  2. Stage III disease – technology advances
  3. advanced in the regulatory space
  4. smaller cohort size to approve a drug
  5. biologic complexity, driver oncogenes, precision to imprecision
  6. cost of risk in investment in innovations
  7. check point inhibitor – known biology and immuno-modulation, data hypothesis and moving forward
  8. Organizational culture, interaction in teams, functional behavior
  9. commit to deliverable, perfect timing contingent on work of others.

Peter Hammerman

  1. single cell tumor immunity in combination drug therapy
  2. Tumor monitoring over time
  3. Novartis is interested to collaborate with innovators in Academia and in other institutions
  4. critical thinking on DATA and on negative data
  5. Combination drug therapy: orthogonal mechanism of actions and drug classed – toxicity is an issue

Shiva Malek

  1. How to drug mutations on DATA
  2. Acquired and intrinsic mutations
  3. exposure and patient safety
  4. UCSF’s Ashkenazi’s Team and Genetech – basic biology area selection
  5. Failure are not talked about
  6. Round table for problem solvers, how you approach a problem
  7. translational work require skills beyond technical expertise
  8. learning the navigation inside an organization
  9. leadership in R&D, expected to demonstrate leadership, the Scientist needs to have command of the field and of desirable directions of research

 

2:00 pm J. Christopher Love (MIT’s Koch Institute)

Acceleration of the PROCESS to develop Precision Medicine products

  • design, build, test – PROCESS
  • New drugs and vaccines – the process is iterative
  • measurements, with use of smallest number of samples
  • deliver precision medical: small f patients or large population or
  • clinical samples provide rich source of information: Blood or tissue sample
  • Tissue – extract RNA, component cells, single-cell RNA sequencing,
  • Challenges of enabling scRNA-seq in clinical labs
  • Probability, scale, capture efficiencies, temporal uniformity
  • single-cell sequencing
  • Seq-Well: method for scRNA-Seq
  • New Chemistries for T-cell
  • Blood: cell, cfDNA, Exosomes
  • map cancer genome from blood
  • Tissue:
  • Single circulating Tumor cells:
  • yield genomic landscape of cancer
  • cell free DNA, vells, proteins, metabolite, Tumor is existence, draw blood
  • cfDNA Tumor Fraction is prognostic of survival in mTNBC
  • automate to 13 cancer types
  • Rs is now possible
  • reduce sample requirement
  • cost is low digital information from clinical samples
  • Keytruda – is a molecular Signature
  • low volume product, advanced preparation (mo-years) __>>> agile solutions (days to years)
  • bentchtop, on-demand manufacturing system: Production, Purification, Formulation
  • hand-free production of formulated G-CSF: comparable to licensed products.
  • Plug and play manufacturing using  InSeq
  • Novel MAbs from patients
  • Many molecules to many products

 

2:40 pm Andrea Califano (Columbia University, System Biology)

Mechanistic Framework for the systematic pharmacological targeting of Non-Oncogene Dependencies – Precise Precision Oncology

  • systematic elucidation od critical cancer cell dependencies
  • drug MOA
  • Tumor dependencies to Drug MOA
  • Tumor heterogeneity
  • ARACNe – regulatory targets of regulatory proteins
  • Combinational Therapy: HER@ inhibitor and JAK1/JAK2 inhibitor
  • Driver Mutations
  • ARACNe; MINDy DIGGIT; Expression VIPER: MetaVIPER
  • Aberrantly activated protein for Prioritizing treatment in patients
  • Checkpoint activity reversal – prioritize drugs based on
  • Tumor model selection: GIST
  • 260 patients, 14 untreatable cancers — N of 1 Study
  • Single cell Studies – active proteins in stem-like progenitor cells
  • Ivermectin Treatment vs Control (7d vs 14d)

 

3:20 pm Networking Break

3:40 pm Jean Zhao (Dana Farber Cancer Institute)

Immunotherapy and Targeted Therapy in Cancer Therapy

  • Targeting cancer with CDK4/6 inhibitors
  • CDK4/6 inhibitors causes tumor regression in breast cancer and regression of CT-26 colorectal cancer
  • CDK4/6DNMT1 inducing viral mimicry
  • PARP inhibitors  changing treatment in ovarian cancer
  • FDA approved three drugs for ovarian cancer
  • p53-null; BRCA-null; myc high – model testing

 

4:20 pm Kenna Mills Shaw (MD Anderson Cancer Center)

  • PM nor a Silver bullet nor a Dream Illusion
  • 2013: not all mutations are equally actionable
  • Context of Biomarkers
  • co-mutations in lung cancer identity – therapeutic vulnerability
  • NGS cost decrease leads to increases in Data generation
  • there are only 125 genes ACTIONABLE IN THE CLINIC
  • finding biomarkers beyond direct targets
  • clinical actionability:80K mutation – 32%
  • patients: No standard treatment available
  • Enrollment inGenotype Matched TRIALS
  • MUTATIONS SCREENED: LACK OF ENROLLMENT NOT DUE TO LACK OF MATCHING PROCESS
  • 69% GOT NEW REGIMEN, 17% did not come back — no one called them
  • 58% enrolled on genotrype-matched trials
  • Beyond NGS:

www.personalizedcancertherapy.org

  • DECISION SUPPORT IN REAL TIME IMPROVES “MATCHING” TO RIGHT DRUG.
  • MULTIFACTORS: CO-MOEBIDITIES, MICROBIOME, IMMUNE PHYNOTYPING, GENOMICS, MICROBIOME, ZIP CODE, INFECTION

5:00 pm Michael Yaffe (MIT)

  • AUGMENTED SYNTHETIC LETHALITY
  • CANCER CELLS ARE UNDER CONSTANT STRESS
  • inflammation
  • Therpeutics-targeted Synthetic Lethality
  • BRCA mutation seen in 10%-20% of patients
  • p53 mutations DNA demage – leads to apoptosis p38 MK2 as a pathway is taking over repair DNA and no apotosis occurs.
  • doxorubicin
  • Nanoparticle targeting of siRNAs to established tumors
  • The Concept of augmented Synthetic Lethality   —- enhance a prevosly known synthetic interaction by targeting additional pathways
  • combination of repair pathway  and checkpoint activation – lead to better therapeutic results
  • MK2 – targets hnRNP A0 (an RNA binding protein)  – Cleaved Caspase 3 – is synthetic lethal with p53 mutuant tumors, not just p53 null alleles
  • MK2 links Inflammation and Cancer – IBD –>> polyps and Colon Cancer
  • myeloid cell recruitment to inflammatory tumors in
  • MK2 KO mice: IL-4 –M2 magrophage – tumor progression; regulate the tumor microenvironment
  • IFNgamma –>M1 macrophages – tumor suppression

 

 

 

SOURCE

https://ki.mit.edu/news/events/cpcmsymposium-2018

https://www.eventbrite.com/e/mit-center-for-precision-cancer-medicine-inaugural-symposium-tickets-50424019600?utm_campaign=event_reminder&utm_medium=email&utm_source=eb_email&utm_term=eventname

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