| Image Credit: © Karsyarina – stock.adobe.com

Chemotherapy doesn’t just kill cancer cells. It also affects the microbes in the digestive tract.

Researchers at UC San Francisco have discovered that some gut bacteria can reduce the side effects of these potent treatments, and that one family of cancer drugs may actually boost these protective bacteria.

The phenomenon could help physicians predict the severity of a patient’s side effects and points the way to supplements that could help those whose guts aren’t sufficiently protecting them.

“These studies emphasize the important relationship between the gut microbiome and drug toxicity,” said 

, PhD, a professor of microbiology and immunology at UCSF. “A more detailed understanding of this relationship could provide new strategies to optimize the treatment of cancer and other diseases.”

Turnbaugh’s team found that colorectal cancer patients taking a class of cancer drugs known as fluoropyrimidines had much less diverse microbiomes in their digestive system. But the surviving bacteria did something amazing.

“They were able to gobble up the chemotherapy and chemically transform it into a harmless byproduct,” said 

, a student in the Medical Scientist Training Program at UCSF who co-authored the study along 

, MD, MPH, an associate professor of medicine who specializes in gastrointestinal cancer. It published April 16 in 

The team also saw that measuring the abundance of helpful bacteria could predict whether a patient would develop the kind of severe side effects, like nausea or vomiting, that make it hard for people to complete their treatment.

When the researchers gave these drug-processing microbes to mice experiencing severe chemotherapy side effects, their symptoms greatly improved, suggesting that humans may be able to use the bacteria as probiotics.

A second study, published May 20 in the journal 

, revealed the microbiome can also protect patients from the painful numbness or tingling sensation that is another common side effect of chemotherapy, by producing vitamin K2.

When the researchers looked at the microbiomes of 56 colon cancer patients, they saw again that the fluoropyrimidine drugs had killed off some of the organisms and bolstered the populations of others.

Among those that thrived during chemotherapy was a nonpathogenic strain of E. coli that produced vitamin K2. The researchers gave K2 to mice who’d been treated with fluoropyrimidine drugs, and their neuropathy resolved.

Patients who reported fewer side effects also had more K2 in their microbiomes.

“For a long time, the microbiome has seemed like a black box,” Kidder said. “We’re now starting to be able to shine little flashlights and find clues to how we can influence it for the better — in this case, better outcomes for cancer patients.”

 Additional authors on the Science Translational Medicine study: Than Kyaw, Taylor Halsey, Christine Olson, Edwin Ortega, Cecilia Noecker, Vaibhav Upadhyay, Dalila Stanfield, Paige Steiding, Benjamin Guthrie, Peter Spanogiannopoulos, Darren Dumlao, Jessie Turnbaugh, Matthew Stachler, Erin Van Blarigan, Alan Venook and Chloe Atreya, of UCSF.

Additional authors on the mBio study include:

 Benjamin Guthrie, Christine Olson, Chen Zhang, Edwin Ortega, Lorenzo Ramirez and Chloe Atreya from UCSF, Lars Hillege, Xueyan Fu, Romy Aarnoutse, Judith de Vos-Geelen , Liselot Valkenburg-van Iersel, Irene van Hellemond, Arnold Baars, Johanna Vestjens, John Penders, Marjolein Smidt and Janine Ziemons of Maastricht University, The Netherlands, and Adam Deutschbauer of Lawrence Berkeley National Laboratory.

 The studies were supported by the National Institutes of Health (grants R01CA255116, R01DK114034, and R01HL122593, F30CA257378, R01HL122593, R01CA255116 and R01DK114034), the USDA (grant 58-8050-3-003) and the Parkinson’s Disease Foundation (grant PF-PRF-932695).

Articles

Researchers at UC San Francisco discovered that some gut bacteria reduce the side effects of chemotherapy and that some drugs boost protective bacteria.

Can Gut Microbes Save Patients From Chemotherapy Side Effects?

Image Credit: © Joshua 
– stock.adobe.com

Leading cancer researchers from UC San Francisco will present talks about advances in targeted therapies, cancer genomics, using AI to personalize cancer treatment, improving diagnosis of hard-to-treat cancers, and other cancer research topics at this year’s annual meeting of the American Association for Cancer Research (AACR) conference, which will be held April 25-30 in Chicago.

The theme of this year’s conference, “Unifying Cancer Science and Medicine: A Continuum of Innovation for Impact,” highlights the latest advances in the biology, prevention, detection, diagnosis, and treatment of cancer, as well as state-of-the-art concepts and technologies shaping cancer research.

This year’s program featured innovative research and discussions by many experts from the UCSF Helen Diller Family Comprehensive Cancer Center.

Plenary Sessions and Symposia (all times Central):

Sunday, April 27, from 9:30 a.m. to 11:30 a.m.

Opening Plenary Session PL02 - Opening Plenary: Unifying Cancer Science and Medicine – A Continuum of Innovation for Impact from 9:40 a.m. to 10:07 a.m.

Kevan M. Shokat, PhD, UCSF professor of Cellular and Molecular Pharmacology and AACR Academy Fellow, presents “Overcoming The Undruggable Nature Of The Most Common Human Oncogene, K-Ras.” Somatic mutations in the small GTPase K-Ras are responsible for approximately 30% of human cancers and are generally associated with poor response to standard therapies. The mutations in K-Ras were identified in the early 1980’s but it took almost four decades for the first drugs targeting the protein to be approved. The long delay was a result of the apparent lack of a drug binding pocket on K-Ras despite detailed structural and biochemical characterization of the protein, leading to it being referred to as “undruggable.” While progress has been made with new medicines, such as sotorasib and adagrasib, being approved for patients with K-Ras (G12C) lung cancer, drug development of agents to inhibit the more frequent K-Ras (G12D) and K-Ras (G12V) versions found in colon and pancreatic cancer, still remains a challenge. Another challenge is drug resistance which is faced by all targeted cancer therapies including the new K-Ras (G12C) directed drugs. In this lecture Shokat will provide a perspective on challenges and opportunities of newly developed K-Ras targeting drugs.

Sunday, April 27, from 1:00 p.m. to 2:30 p.m.

Major Symposium - SY42 - Tissue Mechanics and Physical Forces in Cancer

Valerie M. Weaver, PhD, director of the UCSF Center for Bioengineering & Tissue Regeneration and professor of Surgery in Division of Surgical Oncology, presents “Forcing Cancer Initiation And Progression Through Myeloid Lipid Peroxidation-Mediated DNA Damage” from 1:30 p.m. to 1:50 p.m. Weaver discusses cancer as a physical disease and how the interplay between connective tissue, physical forces and immune response plays a role in cancer risk, cancer aggression and therapy response. She will discuss how the immune system spurs the fibrosis and mechanical changes in tissues that drive cancer and how the immune cells respond to the altered physical properties of that connective tissue, corrupting their anti-tumor response and metabolism. In addition to changing the metabolism, the extracellular matrix and anti-tumor function, myeloid cells produce lipid aldehydes that cause DNA damage and mutations in the cancer tissue. She will examine ways to correct the behavior of corrupted myeloid cells including development of novel treatments.

Sunday, April 27, from 3:00 p.m. to 5:00 p.m.

Mini-symposium MS.CL01.01 - Liquid Biopsy: Circulating Tumor Cells

Laura Huppert, MD, a breast oncologist and assistant professor in the UCSF Division of Hematology/Oncology, presents “Development Of A Novel Assay To Detect Circulating Tumor Cells (CTC) In The Cerebrospinal Fluid Of Patients With Leptomeningeal Disease” (#1147) from 3:50 p.m. to 4:05 p.m. Approximately 5-15% of patients with metastatic breast cancer (MBC) will develop leptomeningeal disease (LMD), characterized by the spread of tumor cells to the lining of the brain and spinal cord. Diagnosis can be limited by the availability to detect tumor cells in the cerebrospinal fluid (CSF) and prognosis of LMD is poor – on the order of less than six months – with limited treatment options. Given the poor prognosis after diagnosis of LMD, improving methods to detect rare CTCs in the CSF could lead to earlier intervention and improved patient outcomes. To address this unmet clinical need, the researchers developed a novel process for detecting and characterizing CTCs in the CSF of patients with LMD and report on the results intended to improve LMD diagnosis and potentially have a positive impact on patient outcomes.

Sunday, April 27, from 6:30 p.m. to 8:30 p.m.

Town Meeting: Session TM07 – Charting the Trajectory for Advancements in Pediatric Cancer Research- A Pediatric Cancer Working Group Town Hall

Alejandro Sweet-Cordero, MD, UCSF chief of Pediatric Oncology and chair of the AACR Pediatric Cancer Working Group, hosts the 2025 PCWG Town Hall which will feature presentations from experts in the pediatric cancer community on the theme of "Charting the Trajectory for Advancements in Pediatric Cancer Research" followed by a panel discussion. The Town Hall also includes a Networking Reception at the beginning of the session.

He also serves as chairperson and presenter for the Major Symposium DC07 - Molecular Tumor Profiling for Pediatric Oncology on Monday, April 28, 2025 from 3:00 p.m. to 4:30 p.m.

Monday, April 28, from 10:15 a.m. to 11:45 a.m.

Major Symposium SY26 - Metabolism and Organelle Biology in Cancer

Rushika Perera, PhD, vice chair of the UCSF Department of Anatomy and chief scientific officer of the UCSF Pancreas Center, is chairperson for the session and presenter of “Decoding Novel Lysosome Functions In Pancreatic Cancer” from 11:20 a.m. to 11:35 a.m. Pancreatic ductal adenocarcinoma (PDAC) is the most common and aggressive cancer of the pancreas. PDAC tumors are highly reliant on nutrient scavenging pathways such as autophagy, and the lysosome to sustain metabolic homeostasis and cellular quality control. To fully understand the functions of the lysosome in PDAC progression, Perera’s lab uses biochemical approaches to isolate intact lysosomes from PDAC cells, followed by mass spectrometry-based proteomics. Using this strategy, the research team has uncovered unique features and functions of PDAC lysosomes that promote cellular adaptation to stress and tumor growth. They have developed techniques to profile lysosome content and composition during different stages of tumor evolution including metastasis to the liver and lungs – the two major sites of secondary tumor growth in PDAC patients. This research highlights how dynamic changes in lysosome composition in vivo, enables PDAC cells to rapidly adapt to growth at different organ sites and may inform the development of therapeutic strategies focused on lysosome inhibition in cancer.

Monday, April 28, from 12:30 p.m. to 2:00 p.m.

Major Symposium SY08 - Developments in RAS Signaling Inhibition: Bench to Bedside

Frank McCormick, PhD, FRS, the David A. Wood Chair of Tumor Biology and Cancer Research and professor in the UCSF Department of Cellular and Molecular Pharmacology, is chairperson for the session and also presents “The End of KRAS cancers?” from 12:35 p.m. to 12:55 p.m. McCormick will provide an overview of some of the approaches that he and others are taking to attack cancers driven by mutant KRAS, and review some of the drugs developed which use different mechanisms to attack this protein. He will also talk about new approaches being employed to further increase the chances of treating these cancers.

Tuesday, April 29, from 8:00 a.m. to 10:00 a.m.

Plenary Session PL04 - Targeting the Cancer Ecosystem

Max F. Krummel, PhD, Robert E. Smith Endowed Chair in Experimental Pathology at UCSF, presents “Leveraging Tumor Immune Archetypes In Treating Cancer” from 8:32 a.m. to 8:59 a.m. This plenary session will address co-evolution of tumor and host at the tissue and systems levels and explore how complexity of the cancer ecosystem presents both challenges and opportunities for therapy. There will be a discussion of therapeutic means to target the complex tumor micro- or macroenvironment and promote new states phenotypically similar to healthy tissues. The session will illustrate the importance of considering the heterocellular tumor ecosystem in efforts to understand and treat cancer and highlight mechanisms of cellular and anatomic crosstalk that may represent therapeutic targets.

Tuesday, April 29, from 10:15 a.m. to 11:45 a.m.

Major Symposium SY05 - Cardio-Oncology: A Novel Platform for Investigation

Javid Moslehi, MD, William Grossman Distinguished Professor in Cardiology and chief of the UCSF Cardio-Oncology & Immunology Program, is chairperson of the session, presenting the symposium introduction as well as the talk “Immune Checkpoint Inhibitors And Cardiac Toxicity: From Mice To Humans” from 11:10 a.m. to 11:30 a.m. In the past 20 years, cardio-oncology has emerged as a new cardiovascular subspecialty in part because of the success that has been attained in oncology. Patients now live longer with the cancer, making cardiovascular health more relevant. Although these therapies have changed the natural course of many cancers, several may also lead to cardiovascular complications. Many new anticancer drugs approved over the past decade are “targeted” therapies that interfere with intracellular signaling contributing to tumor progression. Unexpected cardiovascular and cardiometabolic effects of patient treatment with these inhibitors have provided unique insights into the role of these targets in human cardiovascular biology. The session will address these topics and propose that numerous ongoing oncology clinical trials are an opportunity for closer collaboration between cardiologists and oncologists to study the cardiovascular and cardiometabolic changes caused by the modulation of these pathways in patients and can serve as a potential avenue for optimization of anti-cancer therapies and for cardiovascular research and drug discovery.

Major Symposium SY16 - Novel Classes of Human Cancer Rejection Antigens: Beyond Point Mutations

Hideho Okada, MD, PhD, director of the UCSF Brain Tumor Immunotherapy Center and UCSF professor of Neurological Surgery, Surgery and Immunology, presents “Tumor-Wide RNA Splicing Aberrations Generate Therapeutically Actionable Public Neoantigens” from 10:45 a.m. to 11:05 a.m. T cell-based immunotherapies hold promise in treating cancer by leveraging the immune system's recognition of cancer-specific antigens. However, their efficacy is limited in tumors with few somatic mutations and substantial intratumoral heterogeneity. In this presentation, Okada discusses novel sources of antigens for cancer immunotherapy, including a previously uncharacterized class of tumor-wide public neoantigens originating from RNA splicing aberrations in diverse cancer types. He and his team identified T cell receptor clones capable of recognizing and targeting neoantigens derived from aberrant splicing in GNAS and RPL22. In cases with multi-site biopsies, they detected the tumor-wide expression of the GNAS neojunction in glioma, mesothelioma, prostate cancer and liver cancer. Their study highlights a role for dysregulated splicing factor expression in specific cancer types and their findings establish a molecular basis for T cell-based immunotherapies addressing the challenges of intratumoral heterogeneity.

Major Symposium SY49 - Minorities in Cancer Research Scientific Symposium: Using Self-identified Race/Ethnic Categories in Cancer Disparities Research in the Era of Precision Medicine

Scarlett Lin Gomez, MPH, PhD, co-leader of the UCSF Cancer Control Program and professor in the UCSF Department of Epidemiology and Biostatistics, will present her research from 11:00 a.m. to 11:20 a.m. Over the past 25-years, the science of cancer health disparities research has evolved from first-generation studies that focused on describing population group differences in cancer incidence and mortality to transdisciplinary translational studies that investigate the contribution of biological, behavioral, clinical, and social drivers to cancer care outcomes. While comparisons of racial and ethnic group differences using self-identified categories have been instrumental in identifying populations that are at risk for poor outcomes following diagnosis and treatment, concerns have been raised about using self-identified race/ethnicity in biomedical research. The objective of this session is to review the advantages and disadvantages of using self-identified race/ethnic categories in cancer disparities research and identify best practices for monitoring and addressing the burden of cancer risk across different populations in light of methodologies and instruments that potentially have greater precision in basic, clinical, and population-based research studies.

Gomez also presents “Prevention, Early Detection, Population Sciences, And Disparities Research” from 12:39 p.m. to 1:04 p.m. during Plenary Session PL06 - AACR Annual Meeting 2025 Highlights: Vision for the Future, on Wednesday, April 30, from 12:10 a.m. to 1:30 p.m.

Tuesday, April 29, from 2:30 p.m. to 4:00 p.m.

Mini-symposium MS.ET02.01 - Novel Cancer Therapeutic Targets

Tadashi Manabe, MD, PhD, UCSF post-doctoral scholar, presents “Unveiling The Potent Anti-Tumor Activity And Underlying Mechanism Of Action Of The Novel Pan-RAF Inhibitor Exarafenib In BRAF-Mutated NSCLC” (#6389) from 2:50 p.m. to 3:05 p.m. Manabe will present research on Exarafenib, a novel therapeutic approach that addresses a critical unmet need in lung cancer treatment. Somatic BRAF driver alterations play a crucial role in various cancers, including melanoma and non-small cell lung cancer (NSCLC). These BRAF alterations are classified into three distinct classes based on their oncogenic mechanisms. To determine the frequency of Class 2 and Class 3 mutations in lung cancer, which currently lack treatment options, the researchers collaborated with Guardant Health to analyze a comprehensive database of liquid biopsies from cancer patients. Manabe will report on their clinical findings that include promising responses in two cases with Class 2 BRAF alterations, potentially offering new treatment strategies for patients with BRAF mutations.

Wednesday, April 30, from 10:15 a.m. to 11:45 a.m.

Major Symposium SY29 - Biomolecular Condensates in Cancer: Mechanisms and Therapeutic Opportunities

Xiaokun Shu, PhD, professor in the UCSF Department of Pharmaceutical Chemistry, presents “New Physical Biology Of Oncoprotein Condensates: Differential Regulation Of The Transcriptome By Phase Separation” from 10:45 a.m. to 11:05 a.m. Shu will present his research on Myc, which is an oncoprotein transcription factor that is dysregulated in over half of all human cancers. Dysregulation results in unbalanced Myc activity and leads to tumor development. The molecular mechanism of how mixed dysregulation results in tumorigenesis is still unclear despite more than three decades of research, and there is still no FDA-approved drug against Myc. The goal of the researchers is to develop a therapy to Myc-induced cancer that results from dysregulation and unbalanced power of Myc. Shu reports on the development of a protein-protein interaction reporter to screen a large number of small molecules, identifying potent molecules that are now be testing them in animal models.

UCSF experts highlight leadership in innovative cancer research and education.

AI in Cancer Care, Targeted Therapies Among Cancer Conference Talks

Advances in targeted therapy, cancer genomics and eliminating treatment disparities were among the topics that were presented by leading cancer researchers from UC San Francisco at this year’s annual meeting of the American Association for Cancer Research (AACR) conference, held April 5-10, in San Diego.

The theme of this year’s conference, “Inspiring Science, Fueling Progress, Revolutionizing Care,” showcased the latest advances in the biology, prevention, detection, diagnosis, and treatment of cancer as well as state-of-the-art concepts and technologies shaping cancer research today. The gathering brought together scientists, clinicians, health care professionals, survivors, and patients.

This year’s program featured innovative research and discussions by many experts from the UCSF Helen Diller Family Comprehensive Cancer Center. Here are some highlights:

Leading UCSF Presentations (All times Pacific):

3:00 p.m. – 4:30 p.m. | Measuring Structural and Social Determinants of Health in Cancer Research

, PhD, MPH, a social and behavioral scientist and UCSF associate adjunct professor, served as chairperson of this session and also presented “

Characterizing social and built environments in cancer epidemiology cohorts: Geospatial data and methods

 The session focused on emerging frameworks that emphasize the importance of considering structural and social determinants of health, defined as the conditions in which people are born, grow, work, live, and age (social determinants) and the wider set of forces and systems shaping the conditions of daily life (structural determinants) by the World Health Organization. The session considered these concepts and constructs and relevant conceptual frameworks for understanding their impact on health. Shariff-Marco’s presentations focused on how to study neighborhood attributes, particularly those related to the social and built environments, including conceptual frameworks as well as how to measure these for cancer epidemiologic studies.

2:30 p.m. – 4:00 p.m. | Educational Session: “Genetic Ancestry, Tumor Subtype and Somatic Genomic Landscape”

, MD, an internal medicine specialist and UCSF professor of Medicine, presented “

Genetic ancestry and somatic mutational landscape in >40,000 breast cancer patients

 Genetic ancestry is a variable frequently considered in studies of germline genetic risk. However, less is known about the importance of genetic ancestry in studies of somatic (acquired) mutations in cancer. Ziv discussed different approaches to inferring genetic ancestry using genotype data. In addition, he illustrated how genetic ancestry is related to somatic mutations and copy number aberrations in a dataset of >40,000 breast tumors.

1:00 p.m. – 2:30 p.m. | Major Symposium: Socioeconomic Contributions to Cancer Health Disparities

, MPH, PhD, an epidemiologist and UCSF professor of Epidemiology and Biostatistics, served as chairperson for the symposium and also presented “

Multi-level socioeconomic contributions to cancer health disparities from concept to measurement to practice

 This session reviewed current frameworks for conceptualizing and measuring the impacts of social and socioeconomic factors at multiple levels, and the research examining these factors in adolescent and young adult and in adult cancer patients. The session also addressed solutions for intervening upon social and socioeconomic disparities.

Mini-Symposium: CL01.03 - Biomarkers Predictive of Therapeutic Benefit

, PhD, UCSF Department of Laboratory Medicine, was the presenter for “

Immune subtyping identifies a subset of HR+HER2- early-stage breast cancer patients with a very high likelihood of response to neoadjuvant immunotherapy (IO): Results from 5 IO arms of the I-SPY2 TRIAL

 Wolf reported on the performance of ImPrint in HR+HER2- patients from five immuno-oncology (IO) arms from I-SPY2.2 breast cancer trial. I-SPY2 was the first randomized trial to examine the efficacy of IO therapy in high-risk HR+HER2- breast cancer where most IO arms showed improved efficacy relative to control. The study also previously showed immune-gene expression signatures associate with pathologic complete response (pCR) in HR+HER2- treated with IO, and the research team developed a clinically applicable Immune classifier (ImPrint) predicting response to IO that is now being used in I-SPY2.2 as part of the Response Predictive Subtypes for the trial.

Presidential Select Symposium: Cancer Immunotherapy – Where Do We Go from Here?

, MD, PhD, UCSF professor of Medicine and director of the Gladstone-UCSF Institute of Genomic Immunology, presented “

Decoding and reprogramming T-cell circuits with CRISPR

” at the presidential select symposium from 

 Marson discussed the power of using an emerging set of genomic tools to test every genetic sequence in the genome and write new synthetic genetic sequences to program immune cells to be effective and safe, searching out cancer cells and eliminating them from the body. He also discussed the need to create an interdisciplinary community to bring together different disciplines to unlock the true promise of immunotherapies and produce innovations that will make cancer immunotherapy reach the patients who still desperately need it.

Clinical Trials Plenary Session: Advances in Targeted Therapy

, MD, a medical oncologist, Winterhof Family Endowed Professorship in Breast Cancer, and director of Breast Oncology Trials and Clinical Education at UCSF, was a discussant for 2 UK trials called the 

., reviewing the results of the trials, which explored the impact of “gap scheduling” in order to add a PARP inhibitor to chemotherapy in the safest and most effective manner to improve neoadjuvant response to treatment for patients with early-stage breast cancer. Her talk examined the impact of the gap scheduling on patients who had germline BRCA mutations in contrast to patients who had triple-negative breast cancer and were treated in the neoadjuvant setting.

10:15 a.m. – 11:45 a.m. | Major Symposium: Advances in Pediatric Cancer: Mechanisms, Vulnerabilities, and Translation 

, MD, UCSF chief of Pediatric Oncology, presented 

“Identification of novel osteosarcoma subtypes based on epigenetic and genomic analysis

 This session spotlighted recent advances pertinent to clinically aggressive childhood cancers, including novel epigenetic subtypes of osteosarcoma, and determinants of malignant transformation, disease progression, and treatment response in the pediatric setting. The session also included a discussion of strategies for rapid translation of novel molecular and mechanistic insights into improved diagnostics and treatments for affected children.


Sweet-Cordero also served as chairperson for

Town Hall Meeting: Then and Now: Updates in Pediatric Cancer Predisposition— A Pediatric Cancer Working Group Town Hall Meeting

Sunday, April 7, from 6:00 p.m. – 8:30 p.m

. He is chair of AACR’s Pediatric Cancer Working Group (PCWG).

Mini-symposium: Novel Molecular Targets and Biomarkers

, MS, cancer immunotherapy Ph.D. candidate at UCSF, presented “

Novel public and tumor-wide neoantigens arising from clonal aberrant splicing events drive tumor-specific T-cell responses across diverse cancer types

 Kwok discussed his glioma study, which included development of a novel comprehensive in silico pipeline for detecting tumor-specific splicing events (neojunctions), and across multiple cancer types. He discussed how the research successfully identified a new class of tumor-wide, public, alternatively spliced neoantigens that elicit CD8+ T-cell-mediated immune responses that may offer an off-the-shelf immunotherapy approach that tackles the critical challenge of intratumor heterogeneity in immunotherapy resistance.

, MD, an otolaryngologist and associate vice chancellor for clinical and translational research at UCSF, led a “meet the expert session” on the topic of “

Identifying and Measuring Gender Inequities in Science and Medicine

.” She presented the findings of a qualitative research study she conducted using in-depth, in-person interviews with 52 women and 52 men who were medical school faculty members at 16 institutions across the United States. The study’s goal was to better understand why women scientists experience higher rates of discrimination based on sex. In this session, she explored the institutional metrics that should be evaluated to identify, track, and assess potential interventions designed to mitigate inequities.

10:15 a.m. – 11:45 a.m. | Major Symposium: Health Behavior Practices after Cancer Diagnosis to Deter Cancer Progression and Death: Evidence, Gaps, and Solutions

, ScD, the Steven and Christine Burd-Safeway Distinguished Professor of Epidemiology and Biostatistics at UCSF, served as chairperson for this symposium and presented “

Does exercise or fitness deter cancer progression after diagnosis

 She discussed how evidence is growing that diet and physical activity after a diagnosis of cancer deters cancer-specific and all-cause death. She also discussed the need for innovative solutions to increase nutritional quality and exercise in cancer survivors, in particular among those who are historically under-served and/or of lower socioeconomic status.

Advances in Diagnostics and Therapeutics session: KRAS: Broadening the Attack Beyond G12C with Small Molecules and Immuno-Oncology

, PhD, UCSF professor of Cellular and Molecular Pharmacology and AACR Academy Fellow, chaired this session and presented “

Expanding K-Ras covalent chemistry for targeting K-Ras (G12D)

. While KRAS mutations were a shining example of undruggable cancer targets for decades following their discovery in the early 1980s, the KRAS-G12C inhibitors sotorasib and adagrasib broke a 40-year drought in targeted treatment. While G12C mutations are very prevalent in lung tumors, G12D is the most common KRAS mutation in pancreatic ductal adenocarcinoma as well as colorectal, non-small cell lung, and other cancers, and is much harder to target than G12C. Shokat discussed the latest findings in KRAS chemistry and structure in the continuing search for novel small molecules that target G12D mutations.

12:30 p.m. – 2:00 p.m. | Major Symposium: Discovering and Broadening the Therapeutic Modalities of Immune Therapy

, PhD, professor of Pathology and Robert E. Smith Endowed Chair in Experimental Pathology at UCSF, presented “

Using archetypes and machine learning to discover novel immune pathways for tumor elimination

 Krummel was among the presenters focusing on novel and investigative modalities for improving immune therapy. His discussion looked at using immune archetypes across different tumor microenvironments and machine learning to uncover new approaches for tumor elimination.

12:30 p.m. – 2:00 p.m. | Advances in Prevention Research session: “From Precursors to Prevention: How Research into Cancer Precursor Lesions Creates Prevention Opportunities” 

, MD, PhD a dermatologist and the Gerson and Barbara Bass Bakar Distinguished Professor in Cancer Research at UCSF, presented “

When you come to a fork in the road, take it: Navigating the diverse evolutionary paths from precursor lesions to melanomas

 Bastian described different melanoma subtypes and their evolutionary trajectories from different families of precursor lesions. The varying sequential order in which specific mutations become selected between these ‘pathways’ indicates unappreciated differences in which tumor suppressive mechanisms are engaged and how they are phased during tumor evolution. These differences likely indicate variations in the respective cell of origin, their differentiation and functional stage, determining specific vulnerabilities along which tumor evolution can occur.

Town Hall Meeting: Advancing Radiation Oncology with Artificial Intelligence: A Radiation Science and Medicine Working Group Town Hall Meeting

, PhD, assistant professor in the UCSF department of Radiation Oncology, was an invited speaker presenting “

Causal Targeted Machine Learning for Real-World Evidence Generation in Oncology: Assessing Causal Effects of Radiation Toxicity on Overall Survival in Stage III Non-Small Cell Lung Cancer

.” His study explores the causal impact of radiation-induced toxicities on overall survival in stage III non-small cell lung cancer patients undergoing proton radiation therapy. The study findings suggest the need for personalized treatment strategies that balance treatment intensity with toxicity management. He also explained how the study methodology provides a step-by-step causal roadmap for generating reliable real-world evidence, setting a precedent for applying such techniques in radiation oncology to support clinical and regulatory decision-making, and ultimately enhance patient care.

Major Symposium: Cancer Metabolism Across Scales: From Organelles to Organisms

, PhD, UCSF associate professor of Anatomy, presented “

Lysosome dependent metabolic adaptation in pancreatic cancer

The interdisciplinary session will convene researchers working at the forefront of cancer biology and metabolism and explore how metabolic processes, from organelles to entire organisms, influence cancer development and progression. Perera was among the experts to discuss metabolic reprogramming in cancer cells and the roles that cellular components like mitochondria, lysosomes, and autophagy play in finding new therapies to treat the disease.

Targeted therapy, genomics, and treatment disparities were among the topics that were presented by researchers from UCSF at the 2024 AACR conference.

Advances in Targeted Therapy, Treatment Disparities Among Cancer Conference Talks

Immunotherapies using engineered T cells have ushered in a new era in cancer treatment, but they have their limits. They may cause adverse effects or stop working, and they do not work at all against 90% of cancers.

Now, scientists at UC San Francisco and Northwestern Medicine may have found a way around these limitations by borrowing a few tricks from cancer itself.

By studying mutations in malignant T cells that cause lymphoma, they zeroed in on one that imparted exceptional potency to engineered T cells. The team inserted a gene for this unique mutation into normal human T cells, which made them more than 100 times more potent at killing cancer cells. They kept the tumors at bay for many months, showing no signs of becoming toxic.

While current immunotherapies work only against cancers of the blood and bone marrow, the new approach was able to kill solid tumors derived from skin, lung and stomach tissues in mice. The team has already begun working toward testing this new approach in people.

The breakthrough was inspired by the martial arts principle of using an opponent’s strength against them, said 

, PhD, a co-author on the study and associate professor of microbiology and immunology.

“We’ve used the mutations that give cancer cells their staying power to engineer what we call a ‘Judo T-cell therapy’ that can survive and thrive in the harsh conditions that tumors create,” he said.

Immunotherapy has proved difficult against most cancers because a solid tumor creates an environment focused on sustaining itself, redirecting resources like oxygen and nutrients for its own benefit. Often, cancerous tumors hijack the body’s immune system, causing it to defend, rather than attack, the cancer.

Not only does this impair the ability of regular T cells to target cancer cells, it also undermines the effectiveness of engineered T cells that are used in immunotherapies, which quickly tire against the tumor’s defenses. For immunotherapy treatments to work under those conditions, “We need to give healthy T cells abilities that are beyond what they can naturally achieve,” said Roybal, who is also a member of the 

Gladstone Institute of Genomic Immunology

Using such T cells from patients with lymphoma, the UCSF and Northwestern teams screened 71 mutations, eventually isolating one that proved both potent and non-toxic, subjecting it to a rigorous set of safety tests.

“This approach performs better than anything we’ve seen before,” said Jaehyuk Choi, MD, PhD, an associate professor of medical dermatology, as well as biochemistry and molecular genetics, at Northwestern University Feinberg School of Medicine.

“Our discoveries empower T cells to kill multiple cancer types and have the potential to offer cures to people who have a poor prognosis,” he said, noting that because cell therapies live and grow inside the patient, they can provide long-term immunity against cancer.

In collaboration with the Parker Institute for Cancer Immunotherapy and venture capital firm Venrock, Roybal and Choi have launched a new company, Moonlight Bio, to realize the potential of their “judo” approach. Their first project is developing a lung cancer therapy that they hope to begin testing in people within the next few years.

“We see this as the starting point,” Roybal said. “There’s so much to learn from nature about how we can enhance these cells and tailor them to different types of diseases.”

The research was supported by the Parker Institute for Cancer Immunotherapy, NIH grants (grants F30 CA265107, T32 CA009560, 1DP2AI136599-01 and DP2 CA239143), Cancer Moonshot grant U54 CA244438, the Mark Foundation for Cancer Research, the Bakewell Foundation, and UCSF Helen Diller Family Comprehensive Cancer Center.

Roybal and Choi are inventors on patents related to these discoveries and are co-founders and equity holders in Moonlight Bio.

A genetic mutation that makes cancer cells hardy can be engineered into T cells, giving them superhuman strength.


In Judo Move, Scientists Use Cancer’s Strength to Fight Against It

Many physicians are unfamiliar with how the Food and Drug Administration (FDA) regulates new drugs and medical devices, and they may be under the impression that the data supporting these approvals are more rigorous than they are, according to a national survey of physicians conducted by researchers at UC San Francisco (UCSF).

Physicians said they wanted to see more rigorous pre-market evidence, as well as regulatory action against drugs and devices that do not demonstrate safety and effectiveness after they have been approved for use.

“Many of the physicians we queried felt that the FDA has become more lenient over time,” said first author 

, MD, MHS, a UCSF cardiologist, assistant professor of medicine, and member of the Philip R. Lee Institute for Health Policy Studies. “Physicians need – and want – to know if a drug or device was rigorously studied before they can make recommendations to their patients.”

Physicians’ knowledge of the FDA’s approval process is important in informing clinical decisions and patient discussions. In recent years, several aspects of the FDA review process have changed, including the nature of the evidence required for approval. One of the most prominent modifications is the increasing use of expedited pathways to make potentially promising drugs and devices available to patients based on earlier-stage data.

Among the 509 physicians participating in the survey, 41% reported a moderate or better understanding of the FDA’s drug approval process, and 17% reported a moderate or better understanding of the FDA’s medical device approval process. Fifty-nine percent of physicians thought that the FDA’s current bar for approval of new drugs was about right, with 66% feeling similarly for new devices. Yet, more than a quarter of the respondents thought that the FDA was too flexible in the data accepted for new approvals for both drugs and devices.

Nearly all physicians thought that randomized, blinded trials that met primary endpoints should be required to secure regulatory approval, with majorities saying that the FDA should require two or more randomized controlled trials of most new drugs (57%) and for most new devices (60%). Nearly all physicians thought the FDA should revoke approval for drugs in the accelerated approval program (95%) or breakthrough devices (89%) that did not show benefit in post-approval studies.

“Physicians overwhelmingly felt that randomization, blinding, and meeting primary endpoint thresholds were important characteristics of trials used to support regulatory approval,” Dhruva said. “Despite these preferences, the proportion of studies leading to FDA approval that feature these characteristics has fallen in recent years.”

The authors note that the prevalence of physicians reporting a lack of understanding of drug and medical device approval reflects the limited coverage of these topics during medical education. They also suggest that the FDA could explain clearly and concisely how and why a drug was authorized, including its risk-benefit assessment, and what knowledge gaps remain.

 Rita F. Redberg, MD and Robin Z. Ji, of UCSF; Aaron S. Kesselheim, MD, Zhigang Lu, and Jonathan J. Darrow, SJD, of Harvard University, and Steven Woloshin, MD, of Dartmouth University.

 This study was funded by the Greenwall Foundation and Arnold Ventures.

A national survey conducted by UCSF researchers reveals that many physicians are unfamiliar with how the FDA regulates new drugs and medical devices.

UCSF Helen Diller Family Comprehensive Cancer Center

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