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Department of Surgery Faculty Papers
A Novel PARP Inhibitor Resistance Mechanism Mediated by the RNA-Binding Protein HuR
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A Novel Parp Inhibitor Resistance Mechanism Mediated By The Rna-Binding Protein Hur, Saswati N. Chand, Nicole Meisner-Kober, Shruti Lal, Charles J. Yeo, Md, Jordan M. Winter, Md, Jonathan R. Brody, Md
A Novel Parp Inhibitor Resistance Mechanism Mediated By The Rna-Binding Protein Hur, Saswati N. Chand, Nicole Meisner-Kober, Shruti Lal, Charles J. Yeo, Md, Jordan M. Winter, Md, Jonathan R. Brody, Md
Department of Surgery Faculty Papers
Abstract
Pancreatic ductal adenocarcinoma (PDA) is the 4th leading cause of cancer-related deaths in the United States, and ranks as the third most common cancer associated with BRCA mutations, not including Fanconi Anemia gene mutations such as PALB2. Current combinations of chemotherapeutics have significant toxicities and only minimally extend overall patient survival. Poly-ADP ribose polymerase (PARP) inhibitors (PARPi), which target the DNA damage repair (DDR) pathway, have delivered promising preclinical and clinical results. Although synthetic lethality conferred by PARPi is a promising approach, still “selected” patients with DNA repair-deficient tumors (e.g., BRCA2 mutated) that initially respond to such molecular-targeted therapies …