AACR - 9th April - Targeting DNA repair pathways in the era of immunotherapy26 Mar 2021 15:24
The evidence supporting the AZ / Sierra link continues to build!
https://www.abstractsonline.com/pp8/#!/9325/presentation/220
Presenter/Authors
Lauren Averett Byers. UT MD Anderson Cancer Center, Houston, TX
Disclosures
L. Byers,
AstraZeneca, AbbVie, GenMab, PharmaMar and Sierra Oncology Advisor/Board Member, Consultant/Independent Contractor, Other, Advisory/Consultant Fees and Research Funding.
Genentech, Bristol Myers Squibb, Alethia, Merck and Pfizer Advisor/Board Member, Other, advisor/consultant fees.
ToleroPharmaceuticals Grants/Research Support Recipient.
Abstract
DNA damage response (DDR) pathways hold promise for therapeutic targeting in many cancer types, including small cell lung cancer (SCLC) - a highly recalcitrant cancer with no approved targeted therapies. Inhibitors against DDR targets such as PARP, Aurora kinases, Wee1, and ATR have shown activity in preclinical models, but target-specific and cancer type-specific biomarkers will be important for matching patients to specific DDR inhibitors based on their tumor profiles. Beyond their direct cytotoxic effects, DDR inhibitors may also enhance anti-tumor immunity by activating the innate immune response via the STING pathway. Many clinical trials have recently been launched to evaluate combinations of DDR inhibitors with immune checkpoint blockade, including in SCLC patients receiving frontline therapy. Finally, intratumoral heterogeneity in relapsed SCLC is a driver of therapeutic resistance to chemotherapy as well as DDR inhibitors, suggesting that early use of DDR inhibitors and/or combinations aimed at more than one DDR target may improve responses.
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