Advances in Targeted Therapy, Treatment Disparities Among Cancer Conference Talks

Salma Shariff-Marco, PhD, MPH

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):

Educational Sessions

Friday, April 5

• 3:00 p.m. – 4:30 p.m. | Measuring Structural and Social Determinants of Health in Cancer Research
  Salma Shariff-Marco, 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” from 3:51 p.m. – 4:11 p.m. 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.

Saturday, April 6

• 2:30 p.m. – 4:00 p.m. | Educational Session: “Genetic Ancestry, Tumor Subtype and Somatic Genomic Landscape”
  Elad Ziv, MD, an internal medicine specialist and UCSF professor of Medicine, presented “Genetic ancestry and somatic mutational landscape in >40,000 breast cancer patients” from 3:00 p.m. – 3:20 p.m. 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.

Sunday, April 7

• 1:00 p.m. – 2:30 p.m. | Major Symposium: Socioeconomic Contributions to Cancer Health Disparities
  Scarlett Gomez, 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” from 1:05 p.m. – 1:25 p.m. 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.
• 3:00 p.m. – 5:00 p.m. | Mini-Symposium: CL01.03 - Biomarkers Predictive of Therapeutic Benefit
  Denise Wolf, 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” from 3:05 p.m. – 3:20 p.m. 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.

Monday, April 8

• 10:15 a.m. – 12:00 a.m. | Presidential Select Symposium: Cancer Immunotherapy – Where Do We Go from Here?
  Alexander Marson, 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 11:10 a.m. – 11:30 a.m. 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.
• 10:15 a.m. – 12:15 p.m. | Clinical Trials Plenary Session: Advances in Targeted Therapy
  Hope Rugo, 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 Partner trials. She spoke from 10:45 a.m. – 11:00 a.m., 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 Alejandro Sweet-Cordero, MD, UCSF chief of Pediatric Oncology, presented “Identification of novel osteosarcoma subtypes based on epigenetic and genomic analysis” from 10:45 a.m. – 11:05 a.m. 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 on Sunday, April 7, from 6:00 p.m. – 8:30 p.m. He is chair of AACR’s Pediatric Cancer Working Group (PCWG).
• 2:30 p.m. - 4:30 p.m. | Mini-symposium: Novel Molecular Targets and Biomarkers
  Darwin Kwok, 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” from 2:35 p.m. to 2:50 p.m. 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.
• 5:00 p.m. – 5:45 p.m. | “Meet-the-Expert” session
  Jennifer Ruben Grandis, 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.

Tuesday, April 9

• 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
  June Chan, 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?” from 10:20 a.m. – 10:40 a.m. 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.
• 12:30 p.m. – 2:00 p.m. | Advances in Diagnostics and Therapeutics session: KRAS: Broadening the Attack Beyond G12C with Small Molecules and Immuno-Oncology
  Kevin M. Shokat, 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)” from 12:35 p.m. – 12:55 p.m. 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
  Matthew Krummel, 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” from 1:25 p.m. – 1:45 p.m. 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” Boris Bastian, 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” from 1:25 p.m. – 1:45 p.m. 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.
• 6:00 p.m. – 8:00 p.m. | Town Hall Meeting: Advancing Radiation Oncology with Artificial Intelligence: A Radiation Science and Medicine Working Group Town Hall Meeting
  Gilmer Valdes, 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.

Wednesday, April 10

• 10:15 a.m. – 11:45 a.m. | Major Symposium: Cancer Metabolism Across Scales: From Organelles to Organisms
  ​​​​​​​Rushika Perera, PhD, UCSF associate professor of Anatomy, presented “Lysosome dependent metabolic adaptation in pancreatic cancer” from 11:10 a.m. – 11:30 a.m. 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.