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.
The ASCO Post Staff
Jia Luo, MD, of Dana-Farber Cancer Institute, discusses the emerging class of cancer therapies for allele-specific KRAS inhibitors and the importance of their distinct clinical, genomic, and immunologic features. Because KRAS G12D–mutated non–small cell lung cancer is associated with worse responses to immunotherapy, Dr. Luo believes drug development will need to take these differences into account (Abstract 4117).
The ASCO Post Staff
Nicolas Girard, MD, PhD, of the Institut Curie, discusses findings from the phase III CheckMate 816 trial, which is the first study with an immunotherapy-based combination to demonstrate improved event-free survival and pathologic complete response in the neoadjuvant setting for patients with resectable stage IB to IIIA non–small cell lung cancer. The results may benefit the 30% to 55% of patients whose cancer recurs after surgery (Abstract CT012).
The ASCO Post Staff
Iván Márquez-Rodas, MD, PhD, of Spain’s Hospital General Universitario Gregorio Marañón, discusses final results of the phase II SPOTLIGHT203 study of systemic pembrolizumab in combination with intratumoral BO-112 for patients with advanced melanoma refractory to anti–PD-1–based therapy. The regimen achieved an overall response rate of 25% and a disease control rate of 65% (Abstract CT014).
The ASCO Post Staff
Ari M. VanderWalde, MD, MPH, MBioeth, of The West Clinic, discusses results from the S1616 trial involving patients with metastatic or unresectable melanoma who had primary resistance to PD-1 or PD-L1 inhibitors. Compared with ipilimumab alone, the combination of ipilimumab plus nivolumab benefited some patients: those with tumors that responded to therapy showed an increased amount of CD8+ cells. Because there is no standard treatment for metastatic melanoma after failure of PD-1 inhibitors in BRAF wild-type disease, this research may provide a viable option in the future (Abstract CT013).
The ASCO Post Staff
David A. Barbie, MD, of Dana-Farber Cancer Institute, discusses his laboratory’s studies, showing that malignant pleural mesothelioma, an inflamed cancer type with marginal response to immune checkpoint blockade, demonstrated high tumor cell STING expression and response to STING agonists in combination with natural killer cell therapies ex vivo. STING is the tumor cell stimulator of interferon genes (Abstract 4168).
