Timothy A. Yap, MBBS, PhD, on Developing Novel Therapeutic Strategies to Target DNA Damage Response in the Clinic
AACR Annual Meeting 2022
Timothy A. Yap, MBBS, PhD, of The University of Texas MD Anderson Cancer Center, discusses how research is building on the success of first-generation PARP inhibitors in the clinic and the potential of novel potent PARP1-selective inhibitors, which may lead to improved patient outcomes. Given recent advances in drug discovery, says Dr. Yap, we now can go beyond PARP by drugging other key DNA damage response targets in the clinic, including ATR, WEE1, DNA-PK, RAD51, POLQ, and USP1.
Maria Elena Martinez, PhD, MPH, of the University of California, San Diego Moores Cancer Center, provides an overview of the key components of the Accelerating Colorectal Cancer Screening and Follow-up through Implementation Science program, challenges posed by the COVID-19 pandemic, and opportunities for overcoming these challenges. Although screening and follow-up may reduce the incidence of and mortality from colorectal cancer, these disparities persist in medically underserved populations (Abstract SY30).
Alana L. Welm, PhD, of the University of Utah Huntsman Cancer Institute, discusses her findings of a new pathway that regulates the antitumor immune response during metastatic outgrowth. Interfering with a particular isoform of RON kinase may cause metastatic tumors to be swarmed by T cells and killed, suggesting that new approaches to targeting this kinase may be achievable in the near future (Abstract SY32).
Patricia M. LoRusso, DO, of the Yale University School of Medicine, discusses how patients may benefit in the coming decade from discoveries about agents that target KRAS, and how important the approval of sotorasib turned out to be, as well as other agents in the research pipeline. Dr. LoRusso also talks about the scientific advances in tackling inhibition (Abstract SY20).
Benoit You, MD, PhD, of the Lyon University Hospital (France), discusses phase I/II safety and efficacy results from the ENDOLA trial that combined olaparib with metronomic cyclophosphamide and metformin in patients with advanced pretreated endometrial cancer. At 10 weeks, the non–disease progression rate was 61.5%, reaching the primary endpoint of the study. Median progression-free survival was 5.1 months. Research on biomarkers of efficacy is ongoing (Abstract CT005).
John B.A.G. Haanen, MD, PhD, of the Netherlands Cancer Institute, discusses findings from a phase I study designed to test the safety and efficacy of the CARVac (CAR-T cell-amplifying RNA vaccine) strategy to overcome poor CAR T-cell stimulation and responses in patients with CLDN6-positive advanced solid tumors. Men with testicular cancer in particular showed encouraging responses. Overall, some patients showed long-term CAR T-cell persistence more than 150 days post infusion. Partial responses seemed to deepen further over time (Abstract CT002).