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
Yaqi Zhao, MSc, of St. Jude Children’s Research Hospital, discusses findings from the phase III INO-VATE trial, which showed that inotuzumab ozogamicin reduced the signs and symptoms of acute lymphoblastic leukemia associated with a variety of gene and chromosome changes. Future studies may confirm which patients are more likely to benefit from this agent (Abstract CT027).
The ASCO Post Staff
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).
The ASCO Post Staff
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).
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).
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).
