Pancreatic cancer: BRCA mutation and personalized treatment

Abstract

The highly heterozygous nature of pancreatic cancer is partially responsible for its therapeutic ineffectiveness and resistance. Therefore, the ability to identify subgroups of pancreatic cancer with unique biological characteristics and treatment response is urgently needed. In addition to breast and ovarian cancer, pancreatic cancer is the third most common cancer type that is related to the early onset (BRCA) gene mutation in breast cancer. Mounting evidence has demonstrated that BRCA1/2-mutant breast and ovarian cancers are highly sensitive to DNA damage-related treatment, including poly(ADP-ribose) polymerase inhibitors (PARPi) and platinum-based agents. Preliminary evidence also showed promising results for DNA damage-related treatment in BRCA1/2-mutant pancreatic cancer. Importantly, several prospective clinical trials of PARPi-based regimens are underway for BRCA1/2-mutated pancreatic cancer. Pancreatic cancer with a BRCA1/2 mutation is a small subgroup with a promising therapeutic strategy.

Keywords:

• BRCA1
• BRCA2
• personalized therapy
• platinum
• poly(ADP-ribose) polymerase inhibitors

Financial & competing interests disclosure

This study was supported in part by the Sino-German Center (GZ857), by the Science Foundation of Shanghai (13ZR1407500) and by the National Science Foundation of China (Grant Nos. 81101807). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Key issues

• The highly heterozygous property of pancreatic cancer results in its therapeutic ineffectiveness and resistance.

• Identifying subgroups may aid personalized treatment.

• Pancreatic cancer is the third oncology that related to BRCA genes mutation.

• BRCA1/2 mutation breast and ovarian cancers are sensitive to DNA damage-related treatment including poly(ADP-ribose) polymerase inhibitors (PARPi) and platinums.

• Preliminary evidence showed promising results of DNA damage-related treatment in BRCA1/2 mutation pancreatic cancer.

• Prospective clinical trials are underway for BRCA1/2-mutated pancreatic cancer.

• Pancreatic cancer with BRCA1/2 mutation is a small subgroup with promising therapeutic strategy, which is different from common pancreatic cancer.

• Tumors with germline and somatic BRCA mutation and deficiencies in DNA repair may be sensitive to DNA damage-related treatment.