Christine A. Iacobuzio-Donahue, MD, PhD, of Memorial Sloan Kettering Cancer Center, discusses her research on the evolutionary features of advanced stage pancreatic cancers and the insights that may be used to help improve patient outcomes (Abstract PL05).
Priscilla K. Brastianos, MD, of Harvard Medical School and Massachusetts General Hospital, talks about her efforts to better understand how brain metastases evolve genomically and to test such agents as abemaciclib, paxalisib, and entrectinib, which may stop their growth. Palbociclib, a CDK inhibitor, has already shown potential benefit. A national cooperative group trial is underway in multiple centers to identify novel treatments for patients with brain metastases, who typically have a poor prognosis (Abstract SY38).
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).
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.
Silvia C. Formenti, MD, of Weill Cornell Medicine, discusses research on the best way to integrate radiotherapy with immune modifiers, which might require changes in standard radiation oncology practices. Variables such as the type of treatment fields, the inclusion of draining nodal stations, the degree of exposure of circulating immune cells, the type of dose fractionation, and the timing of radiotherapy during immune checkpoint blockade all can affect the success of immunoradiotherapy combinations (Abstract SY43).
Timothy A. Yap, MBBS, PhD, of The University of Texas MD Anderson Cancer Center, discusses results from a phase Ib expansion trial of the safety and efficacy of the oral ataxia telangiectasia and Rad3-related (ATR) inhibitor elimusertib in advanced solid tumors with DNA damage response defects. Elimusertib is a selective inhibitor of ATR, a key regulator of responses to DNA damage and replication stress, with antitumor activity in preclinical models of various solid tumors and lymphoma (Abstract CT006).
