Spectrum of Response to Platinum and PARP Inhibitors in Germline BRCA–Associated Pancreatic Cancer in the Clinical and Preclinical Setting

Chani Stossel,  Maria Raitses-Gurevich, Dikla Atias, Tamar Beller, Yulia Glick Gorman, Sharon Halperin, Eyal Peer, Robert E. Denroche, Amy Zhang, Faiyaz Notta, Julie M. Wilson, Grainne M. O’Kane, Elina Haimov Talmoud, Nora Amison, Michael Schvimer, Seth J. Salpeter, Vered Bar, Adi Zundelevich, Itay Tirosh, Rotem Tal, Gal Dinstag, Yaron Kinar,  Yonatan Eliezer, Uri Ben-David, Nancy S. Gavert, Ravid Straussman, Steven J. Gallinger, Raanan Berger, Talia Golan.
August, 2023

In this paper, as part of a collaboration with Sheba hospital, we investigated mechanisms of resistance to PARP inhibitors among BRCA+ patients in PDAC. We found that ENLIGHT was predictive of response to PARPi, and an investigation of the ENLIGHT biomarker highlighted the importance of the upregulation of genes involved in the G2–M cell-cycle checkpoint and focal adhesion pathways, which are known to be associated with resistance.

 

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