PARP Inhibitors in Pancreatic Cancer: From Phase I to Plenary Session

Rajvi Patel, Daniel Fein, Carolina B. Ramirez, Kevin Do and Muhammad W. Saif*

PARP Inhibitors in Pancreatic Cancer: From Phase I to Plenary Session.

Survival rates for pancreatic cancer remain dismal. Current standard of care treatment regimens provide transient clinical benefit but eventually chemoresistance develops. Tumors deficient in deoxyribonucleic acid damage repair mechanisms such as BRCA mutants show better responses to platinum based agents, however, such tumors can utilize the poly polymerase pathway as a salvage mechanism.

Therefore, inhibition of PARP pathway could lead to tumor destruction and synthetic lethality in presence of BRCA mutation. Various PARP inhibitors have been approved for treatment
of patients with germline or somatic BRCA mutant breast and ovarian cancer. This provides basis of using PARP inhibitors in patients with pancreatic cancer that harbor BRCA mutation.

A recent phase III Pancreas Cancer Olaparib Ongoing study showed impressive results with near doubling of progression free survival compared to placebo. These results highlight the importance of germline testing for all patients with pancreatic cancer and inclusion of additional deficiencies
in homologous recombination repair including BRCA variants of uncertain significance should be further explored.

The fatality of pancreatic ductal adenocarcinoma continues to rise regardless of current efforts to improve survival. Given the subtle clinical presentation, most patients have advanced
disease at the time of diagnosis.

Hence, the 5-year-survival rate is 3% and the median overall survival is around 6-months for
patients with metastatic disease.

Pancreas Open J. 2019; 3(1): e5-e8. doi: 10.17140/POJ-3-e011

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