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Real Time Conference Coverage: Advancing Precision Medicine Conference,Morning Session Track 1 October 3 2025

Posted in Biological Networks, Cancer Genomics, Clinical Genomics, Evidence-based decision-making, Nobel Prize Winners, REAL TIME Conference Coverage Twitter's Hashtags and Handles per Presentation/session, Single Cell Genomics, Transcriptomics, Translational Research, Translational Science, tagged , , , , , , , , , , , , on October 3, 2025| Leave a Comment »

Real Time Conference Coverage: Advancing Precision Medicine Conference,Morning Session Track 1 October 3 2025

Reporter: Stephen J. Williams, PhD

Leaders in Pharmaceutical Business Intellegence will be covering this conference LIVE over X.com at

@pharma_BI

@StephenJWillia2

@AVIVA1950

@AdvancingPM

using the following meeting hashtags

#AdvancingPM #precisionmedicine #WINSYMPO2025

 

Agenda Track 1: WIN Symposium

8:40 – 9:00

Welcome and Introduction

William G Kaelin, Jr, MD

Wafik S. El-Deiry, MD, PhD, FACP, Chair, WIN Consortium, Director, Legorreta Cancer Center Brown University, Director, Joint Program in Cancer Biology, Brown University and Brown University Health; Associate Dean, Oncologic Sciences, Warren Alpert Medical School, Brown University; Attending Physician, Hematology/Oncology, Brown University Health Mencoff Family University; Professor of Medical Science, Professor of Pathology and Laboratory Medicine, Brown University; Professor,American Cancer Society Research Professor

Dr. El-Diery welcomes all to this joint symposium with Advancing Precision Medicine and the Win Consortium, which he is currently the head of.  More in the WIN Consortium: (Worldwide Innovation Network Consortium in Precision Oncology).  The WIN Network  is involved in setting up internationalclinical tumor board collaboration

Source: https://winconsortium.org/ 

WIN was formed on the premise that we can accomplish more together than each organization can achieve working alone. We aim to improve cancer patients’ survival and quality of life. View WIN’s history and unique attributes:

Clinical trials, projects and publications

WIN members collaboratively design and carry out global studies designed to achieve breakthroughs for patients worldwide. Our distinguished Scientific Advisory Board oversees WIN studies. Current trials include:

View a summary of the WIN Consortium here:

Click to access Brochure_WIN_v24.0_2025_08_13__.pdf

They guide WIN’s strategic, operational, and scientific direction.

Organization Photo

OrganizationThe WIN Consortium is organized in the following groups who collectively work together to achieve WIN’s common goals

 

 

William G Kaelin, Jr, MD

Nigel Russell, Founder and CEO, Advancing Precision Medicine

William G Kaelin, Jr, MD

Christopher P. Molineaux, President & Chief Executive Officer, Life Science Pennsylvania

Life Sciences Pennsylvania (LSPA) is the statewide trade association for the commonwealth’s life sciences industry. Founded in 1989, LSPA works to ensure Pennsylvania has a business and public policy climate that makes the commonwealth the most attractive location to open and operate a life sciences company. Our membership is comprised of organizations statewide, representing the entire ecosystem of the life sciences: research institutions, biotechnology, medical device, diagnostic, pharmaceutical, and investment entities, along with service providers who support the industry. Together, we unify Pennsylvania’s innovators to make the Commonwealth a global life sciences leader.

As president & CEO of Life Sciences Pennsylvania, Christopher Molineaux serves as the chief advocate and spokesman for the life sciences industry that calls Pennsylvania home. Molineaux oversees the strategic direction for the association, assuring Life Sciences Pennsylvania continues to be the catalyst that makes Pennsylvania the top location for life sciences companies.

Molineaux brings to Life Sciences Pennsylvania more than 25 years of experience in the bio-pharmaceutical and health care industries, with front-line experience in developing and executing strategies to navigate a shifting economic and political environment.

9:00-9:40

Keynote Lecture – WIN Consortium

Targeting the Achilles’ Heel of Cancer: Synthetic Lethality and Hypoxia in Precision Oncology

William G Kaelin, Jr, MD

William G. Kaelin, Jr, MD,  2019 Nobel Laureate, Sidney Farber Professor, Harvard Medical School and Dana-Farber Cancer Institute

William Kaelin was born in New York City. He studied chemistry and mathematics at Duke University in Durham, North Carolina, and received his doctor of medicine degree there in 1982. He then did his residency at Johns Hopkins University in Baltimore, Maryland. In 2002 he became a professor at Harvard Medical School in Cambridge, Massachusetts.

Work

 

Animals need oxygen for the conversion of food into useful energy. The importance of oxygen has been understood for centuries, but how cells adapt to changes in levels of oxygen has long been unknown. William Kaelin, Peter Ratcliffe, and Gregg Semenza discovered how cells can sense and adapt to changing oxygen availability. During the 1990s they identified a molecular machinery that regulates the activity of genes in response to varying levels of oxygen. The discoveries may lead to new treatments of anemia, cancer and many other diseases.

To cite this section
MLA style: William G. Kaelin Jr – Facts – 2019. NobelPrize.org. Nobel Prize Outreach 2025. Fri. 3 Oct 2025. <https://www.nobelprize.org/prizes/medicine/2019/kaelin/facts/>

From his Nobel award ceremony:

Gregg Semenza and Sir Peter Ratcliffe decided, independently, to find out how the erythropoietin gene can have such an extraordinary ability to react when oxygen levels drop. Semenza discovered an essential DNA element. Ratcliffe was on the same track and they showed that the element is active in all cells. Oxygen sensing thus takes place everywhere in our bodies. Semenza then discovered the critical player that acti- vates our defense genes. It was named HIF. HIF was subjected to an advanced form of control. It is continuously produced, but when oxygen is ample, it disappears. Only when oxygen levels drop, HIF will remain and can mobilise our defense.

William Kaelin studied a different problem, von Hippel- Lindau disease, with inherited increased risk of certain types of cancer. Cancer cells without the gene, VHL, had activated genes normally controlled by HIF. Sir Peter Ratcliffe proved, in a crucial experiment, that VHL is required for HIF to be removed.

But what was the signal to VHL that HIF needs to disappear?
In the early 2000s, Kaelin and Ratcliffe both solved this mystery. The signal was formed by attaching oxygen atoms onto HIF.
Without oxygen, no signal to VHL, HIF is left intact and can activate our defense.

Piece by piece of the puzzle, the Laureates explained a sensitive machinery that compensates when the vital oxygen is not available in exactly the right amount.

Today we know that the machinery affects a vast range of functions.
When oxygen is lacking, oxygen transport is enhanced by generation of new blood vessels and red blood cells. Our cells are also instructed to economize with the oxygen available, by reprogramming their energy metabolism. Oxygen sensing is also involved in many diseases. As a result of the Laureates’ discoveries, intense activities are under way to develop treatments against for example anemia and cancer.

Professors Semenza, Ratcliffe and Kaelin,
Your groundbreaking discoveries have shed light on a beautiful mechanism explaining our ability to sense and react to fluctuating oxygen levels. The system you have clarified is of fundamental importance for all aspects of physiology and for many human diseases. Without it, animal life would not be possible on this planet.

On behalf of the Nobel Assembly at Karolinska Institutet, it is my great privilege to convey to you our warmest congratulations. I now ask you to step forward to receive the Nobel Prize from the hands of His Majesty the King.

TRACK 1  204BC

 

WIN SYMPOSIUM

MULTI-OMICS

9:40 – 10:40

SESSION 1

From Base Pairs To Better Care:

AI and Omics in Precision Oncology

9:40-10:00

Multi-Omic Profiling and Clinical Decision Support in Precision Oncology

Andrea Ferreira-Gonzalez

David Spetzler, PhD, MBA, MS,  President, Caris Life Sciences

10:00-10:20

Integrating Omics and AI for Next-Gen Precision Oncology

Andrea Ferreira-Gonzalez

Keith T. Flaherty, MD, FAACR, Director of Clinical Research, Massachusetts General Cancer Center; Professor of Medicine, Harvard Medical School;
President-Elect: 2025-2026, American Association for Cancer Research (AACR) 

10:20-10:40

Real-World Data and AI in Precision Oncology: Making Data Work for Patients – Q&A

Andrea Ferreira-Gonzalez

MODERATOR: Jeff Elton, PhD, Vice Chairman, Founding CEO
ConcertAI

Andrea Ferreira-Gonzalez

PANELISTS: David Spetzler, PhD, MBA, MS, President, Caris Life Sciences

Andrea Ferreira-Gonzalez

Keith T. Flaherty, MD, FAACR, Director of Clinical Research, Massachusetts General Cancer Center; Professor of Medicine, Harvard Medical School;
President-Elect: 2025-2026, American Association for Cancer Research (AACR) 

0:40 – 11:10

Break and Exhibits

TRACK 1  204BC

TRACK 2  204A

WIN SYMPOSIUM

MULTI-OMICS

11:10 – 1:10

SESSION 2

The Evolution of Precision Oncology:

Integrating MRD, AI, and Beyond

11:10-12:00

Precision Cancer Consortium

Andrea Ferreira-Gonzalez

Gabriele Allegri, MBA, Vice President, Global Commercial Precision Medicine, Johnson & Johnson Innovative Medicine

Andrea Ferreira-Gonzalez

Shruti Mathur, MS, Pharma Diagnostic Strategy Leader, Global Product Strategy (GPS), Genentech

Andrea Ferreira-Gonzalez

Daryl Pritchard, PhD, Interim President, Personalized Medicine Coalition

Andrea Ferreira-Gonzalez

Keith T. Flaherty, MD, FAACR, Director of Clinical Research, Massachusetts General Cancer Center; Professor of Medicine, Harvard Medical School;
President-Elect: 2025-2026, American Association for Cancer Research (AACR) 

SESSION 3

The Shifting Landscape:

Tumor Plasticity and Resistance

12:00-12:20

Mathematical and Evolutionary Modeling in Precision Radiation Oncology

Andrea Ferreira-Gonzalez

Jacob Scott, MD, DPhil, Professor and Staff Physician-Scientist, CWRU School of Medicine and Cleveland Clinic

12:20-12:40

Plasticity and Persistence: The Role of EMT in Cancer Progression and Therapy Resistance

Andrea Ferreira-Gonzalez

Sendurai A. Mani, PhD, Professor of Pathology and Laboratory Medicine, Brown University; Associate Director of Translational Oncology, Brown University Legorreta Cancer Center

12:40-1:00

Targeting Molecularly Defined Subsets: Challenges in Translational Oncology

Andrea Ferreira-Gonzalez

Benedito A. Carneiro, MD, MS, Director, Clinical Research
Director, Cancer Drug Development; Associate Director, Division of Hematology/Oncology
Legorreta Cancer Center, Brown University Health

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AACR Congratulates Dr. William G. Kaelin Jr., Sir Peter J. Ratcliffe, and Dr. Gregg L. Semenza on 2019 Nobel Prize in Physiology or Medicine

Posted in Anaerobic Glycolysis, CANCER BIOLOGY & Innovations in Cancer Therapy, cancer metabolism, Cell Biology, Cell Biology, Signaling & Cell Circuits, tumor microenvironment, Warburg effect, tagged , , , , , , , , , on October 10, 2019| Leave a Comment »

AACR Congratulates Dr. William G. Kaelin Jr., Sir Peter J. Ratcliffe, and Dr. Gregg L. Semenza on 2019 Nobel Prize in Physiology or Medicine

Reporter: Stephen J. Williams, PhD

 

from The American Association for Cancer Research aacr.org:

 

AACR Congratulates Dr. William G. Kaelin Jr., Sir Peter J. Ratcliffe, and Dr. Gregg L. Semenza on 2019 Nobel Prize in Physiology or Medicine

10/7/2019

PHILADELPHIA — The American Association for Cancer Research (AACR) congratulates Fellow of the AACR Academy William G. Kaelin Jr., MD, Sir Peter J. Ratcliffe, MD, FRS, and AACR member Gregg L. Semenza, MD, PhD, on receiving the 2019 Nobel Prize in Physiology or Medicine for their discoveries of how cells sense and adapt to oxygen availability.

Kaelin, professor of medicine at the Dana-Farber Cancer Institute and Harvard Medical School in Boston; Ratcliffe, director of Clinical Research at the Francis Crick Institute in London; and Semenza, director of the Vascular Program at the Institute for Cell Engineering at Johns Hopkins University School of Medicine in Baltimore, are being recognized by the Nobel Assembly at the Karolinska Institute for identifying the molecular machinery that regulates the activity of genes in response to varying levels of oxygen, which is one of life’s most essential adaptive processes. Their work has provided basic understanding of several diseases, including many types of cancer, and has laid the foundation for the development of promising new approaches to treating cancer and other diseases.

Kaelin, Ratcliffe, and Semenza were previously recognized for this work with the 2016 Lasker-DeBakey Clinical Medical Research Award.

Kaelin’s research focuses on understanding how mutations affecting tumor-suppressor genes cause cancer. As part of this work, he discovered that a tumor-suppressor gene called von Hippel–Lindau (VHL) is involved in controlling the cellular response to low levels of oxygen. Kaelin’s studies showed that the VHL protein binds to hypoxia-inducible factor (HIF) when oxygen is present and targets it for destruction. When the VHL protein is mutated, it is unable to bind to HIF, resulting in inappropriate HIF accumulation and the transcription of genes that promote blood vessel formation, such as vascular endothelial growth factor (VEGF). VEGF is directly linked to the development of renal cell carcinoma and therapeutics that target VEGF are used in the clinic to treat this and several other types of cancer.

Kaelin has been previously recognized with numerous other awards and honors, including the 2006 AACR-Richard and Hinda Rosenthal Award.

Ratcliffe independently discovered that the VHL protein binds to HIF. Since then, his research has focused on the molecular interactions underpinning the binding of VHL to HIF and the molecular events that occur in low levels of oxygen, a condition known as hypoxia. Prior to his work on VHL, Ratcliffe’s research contributed to elucidating the mechanisms by which hypoxia increases levels of the hormone erythropoietin (EPO), which leads to increased production of red blood cells.

Semenza’s research, which was independent of Ratcliffe’s, identified in exquisite detail the molecular events by which the EPO gene is regulated by varying levels of oxygen. He discovered HIF and identified this protein complex as the oxygen-dependent regulator of the EPO gene. Semenza followed up this work by identifying additional genes activated by HIF, including showing that the protein complex activates the VEGF gene that is pivotal to the development of renal cell carcinoma.

The recognition of Kaelin and Semenza increases the number of AACR members to have been awarded a Nobel Prize to 70, 44 of whom are still living.

The Nobel Prize in Physiology or Medicine is awarded by the Nobel Assembly at the Karolinska Institute for discoveries of major importance in life science or medicine that have changed the scientific paradigm and are of great benefit for mankind. Each laureate receives a gold medal, a diploma, and a sum of money that is decided by the Nobel Foundation.

The Nobel Prize Award Ceremony will be Dec. 10, 2019, in Stockholm.

Please find following articles on the Nobel Prize and Hypoxia in Cancer on this Open Access Journal:

2018 Nobel Prize in Physiology or Medicine for contributions to Cancer Immunotherapy to James P. Allison, Ph.D., of the University of Texas, M.D. Anderson Cancer Center, Houston, Texas. Dr. Allison shares the prize with Tasuku Honjo, M.D., Ph.D., of Kyoto University Institute, Japan

The History, Uses, and Future of the Nobel Prize, 1:00pm – 6:00pm, Thursday, October 4, 2018, Harvard Medical School

2017 Nobel prize in chemistry given to Jacques Dubochet, Joachim Frank, and Richard Henderson  for developing cryo-electron microscopy

Tumor Ammonia Recycling: How Cancer Cells Use Glutamate Dehydrogenase to Recycle Tumor Microenvironment Waste Products for Biosynthesis

Hypoxia Inducible Factor 1 (HIF-1)[7.9]

 

 

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Crucial role of Nitric Oxide in Cancer

Posted in Biological Networks, Gene Regulation and Evolution, Biomarkers & Medical Diagnostics, CANCER BIOLOGY & Innovations in Cancer Therapy, Cell Biology, Signaling & Cell Circuits, Chemical Genetics, Disease Biology, Small Molecules in Development of Therapeutic Drugs, Genome Biology, Genomic Testing: Methodology for Diagnosis, Medical and Population Genetics, Metabolomics, Nitric Oxide in Health and Disease, Personalized and Precision Medicine & Genomic Research, Pharmaceutical R&D Investment, Population Health Management, Genetics & Pharmaceutical, Reproductive Andrology, Embryology, Genomic Endocrinology, Preimplantation Genetic Diagnosis and Reproductive Genomics, Systemic Inflammatory Response Related Disorders, Technology Transfer: Biotech and Pharmaceutical, tagged , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , on October 16, 2012| 21 Comments »

Author and Curator: Ritu Saxena, Ph.D.

Screen Shot 2021-07-19 at 7.09.49 PM

Word Cloud By Danielle Smolyar

Introduction

Nitric oxide (NO) is a lipophilic, highly diffusible and short-lived molecule that acts as a physiological messenger and has been known to regulate a variety of important physiological responses including vasodilation, respiration, cell migration, immune response and apoptosis. Jordi Muntané et al

NO is synthesized by the Nitric Oxide synthase (NOS) enzyme and the enzyme is encoded in three different forms in mammals: neuronal NOS (nNOS or NOS-1), inducible NOS (iNOS or NOS-2), and endothelial NOS (eNOS or NOS-3). The three isoforms, although similar in structure and catalytic function, differ in the way their activity and synthesis in controlled inside a cell. NOS-2, for example is induced in response to inflammatory stimuli, while NOS-1 and NOS-3 are constitutively expressed.

Regulation by Nitric oxide

NO is a versatile signaling molecule and the net effect of NO on gene regulation is variable and ranges from activation to inhibition of transcription.

The intracellular localization is relevant for the activity of NOS. Infact, NOSs are subject to specific targeting to subcellular compartments (plasma membrane, Golgi, cytosol, nucleus and mitochondria) and that this trafficking is crucial for NO production and specific post-translational modifications of target proteins.

Role of Nitric oxide in Cancer

One in four cases of cancer worldwide are a result of chronic inflammation. An inflammatory response causes high levels of activated macrophages. Macrophage activation, in turn, leads to the induction of iNOS gene that results in the generation of large amount of NO. The expression of iNOS induced by inflammatory stimuli coupled with the constitutive expression of nNOS and eNOS may contribute to increased cancer risk. NO can have varied roles in the tumor environment influencing DNA repair, cell cycle, and apoptosis. It can result in antagonistic actions including DNA damage and protection from cytotoxicity, inhibiting and stimulation cell proliferation, and being both anti-apoptotic and pro-apoptotic. Genotoxicity due to high levels of NO could be through direct modification of DNA (nitrosative deamination of nucleic acid bases, transition and/or transversion of nucleic acids, alkylation and DNA strand breakage) and inhibition of DNA repair enzymes (such as alkyltransferase and DNA ligase) through direct or indirect mechanisms. The Multiple actions of NO are probably the result of its chemical (post-translational modifications) and biological heterogeneity (cellular production, consumption and responses). Post-translational modifications of proteins by nitration, nitrosation, phosphorylation, acetylation or polyADP-ribosylation could lead to an increase in the cancer risk. This process can drive carcinogenesis by altering targets and pathways that are crucial for cancer progression much faster than would otherwise occur in healthy tissue.

NO can have several effects even within the tumor microenvironment where it could originate from several cell types including cancer cells, host cells, tumor endothelial cells. Tumor-derived NO could have several functional roles. It can affect cancer progression by augmenting cancer cell proliferation and invasiveness. Infact, it has been proposed that NO promotes tumor growth by regulating blood flow and maintaining the vasodilated tumor microenvironment. NO can stimulate angiogenesis and can also promote metastasis by increasing vascular permeability and upregulating matrix metalloproteinases (MMPs). MMPs have been associated with several functions including cell proliferation, migration, adhesion, differentiation, angiogenesis and so on. Recently, it was reported that metastatic tumor-released NO might impair the immune system, which enables them to escape the immunosurveillance mechanism of cells. Molecular regulation of tumour angiogenesis by nitric oxide.

S-nitrosylation and Cancer

The most prominent and recognized NO reaction with thiols groups of cysteine residues is called S-nitrosylation or S-nitrosation, which leads to the formation of more stable nitrosothiols. High concentrations of intracellular NO can result in high concentrations of S-nitrosylated proteins and dysregulated S-nitrosylation has been implicated in cancer. Oxidative and nitrosative stress is sensed and closely associated with transcriptional regulation of multiple target genes.

Following are a few proteins that are modified via NO and modification of these proteins, in turn, has been known to play direct or indirect roles in cancer.

NO mediated aberrant proteins in Cancer

Bcl2

Bcl-2 is an important anti-apoptotic protein. It works by inhibiting mitochondrial Cytochrome C that is released in response to apoptotic stimuli. In a variety of tumors, Bcl-2 has been shown to be upregulated, and it has additionally been implicated with cancer chemo-resistance through dysregulation of apoptosis. NO exposure causes S-nitrosylation at the two cysteine residues – Cys158 and Cys229 that prevents ubiquitin-proteasomal pathway mediated degradation of the protein. Once prevented from degradation, the protein attenuates its anti-apoptotic effects in cancer progression. The S-nitrosylation based modification of Bcl-2 has been observed to be relevant in drug treatment studies (for eg. Cisplatin). Thus, the impairment of S-nitrosylated Bcl-2 proteins might serve as an effective therapeutic target to decrease cancer-drug resistance.

p53

p53 has been well documented as a tumor suppressor protein and acts as a major player in response to DNA damage and other genomic alterations within the cell. The activation of p53 can lead to cell cycle arrest and DNA repair, however, in case of irrepairable DNA damage, p53 can lead to apoptosis. Nuclear p53 accumulation has been related to NO-mediated anti-tumoral properties. High concentration of NO has been found to cause conformational changes in p53 resulting in biological dysfunction.. In RAW264.7, a murine macrophage cell line, NO donors induce p53 accumulation and apoptosis through JNK-1/2.

HIF-1a

Hypoxia-inducible factor 1 (HIF1) is a heterodimeric transcription factor that is predominantly active under hypoxic conditions because the HIF-1a subunit is rapidly degraded in normoxic conditions by proteasomal degradation. It regulates the transciption of several genes including those involved in angiogenesis, cell cycle, cell metabolism, and apoptosis. Hypoxic conditions within the tumor can lead to overexpression of HIF-1a. Similar to hypoxia-mediated stress, nitrosative stress can stabilize HIF-1a. NO derivatives have also been shown to participate in hypoxia signaling. Resistance to radiotherapy has been traced back to NO-mediated HIF-1a in solid tumors in some cases.

PTEN

Phosphatase and tensin homolog deleted on chromosome ten (PTEN), is again a tumor suppressor protein. It is a phosphatase and has been implicated in many human cancers. PTEN is a crucial negative regulator of PI3K/Akt signaling pathway. Over-activation of PI3K/Akt mediated signaling pathway is known to play a major role in tumorigenesis and angiogenesis. S-nitrosylation of PTEN, that could be a result of NO stress, inhibits PTEN. Inhibition of PTEN phosphatase activity, in turn, leads to promotion of angiogenesis.

C-Src

C-src belongs to the Src family of protein tyrosine kinases and has been implicated in the promotion of cancer cell invasion and metastasis. It was demonstrated that S-nitrosylation of c-Src at cysteine 498 enhanced its kinase activity, thus, resulting in the enhancement of cancer cell invasion and metastasis.

Reference:

Muntané J and la Mata MD. Nitric oxide and cancer. World J Hepatol. 2010 Sep 27;2(9):337-44. http://www.ncbi.nlm.nih.gov/pubmed/21161018

Wang Z. Protein S-nitrosylation and cancer. Cancer Lett. 2012 Jul 28;320(2):123-9. http://www.ncbi.nlm.nih.gov/pubmed/22425962

Ziche M and Morbidelli L. Molecular regulation of tumour angiogenesis by nitric oxide. Eur Cytokine Netw. 2009 Dec;20(4):164-70.http://www.ncbi.nlm.nih.gov/pubmed/20167555

Jaiswal M, et al. Nitric oxide in gastrointestinal epithelial cell carcinogenesis: linking inflammation to oncogenesis. Am J Physiol Gastrointest Liver Physiol. 2001 Sep;281(3):G626-34. http://www.ncbi.nlm.nih.gov/pubmed/11518674

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