1. Targeting BRCA and DNA Damage Repair Genes in GI Cancers: Pathophysiology and Clinical Perspectives
- Author
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Andreas Seeber, Alberto Puccini, Kai Zimmer, and Florian Kocher
- Subjects
Cancer Research ,animal structures ,endocrine system diseases ,Somatic cell ,molecular profiling ,BRCA ,Review ,gastrointenstinal cancer ,Germline ,DNA sequencing ,PARP inhibitors (PARPi) ,Breast cancer ,DNA damage repair ,Medicine ,Allele ,skin and connective tissue diseases ,Gene ,RC254-282 ,Polymerase ,biology ,business.industry ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.disease ,female genital diseases and pregnancy complications ,Pathophysiology ,Oncology ,precision oncology ,biology.protein ,Cancer research ,business - Abstract
Mutated germline alleles in the DNA damage repair (DDR) genes “breast cancer gene 1” (BRCA1) andBRCA2have originally been identified as major susceptibility genes in breast and ovarian cancers. With the establishment and approval of more cost-effective gene sequencing methods, germline and somaticBRCAmutations have been detected in several cancers. Since the approval of poly (ADP)-ribose polymerase inhibitors (PARPi) forBRCA-mutated cancers,BRCAmutations gained rising therapeutic implications. The impact and significance ofBRCAmutations have been evaluated extensively in the last decades. Moreover, other genes involved in the DDR pathway, such asATM,ATR, orCHK1, have emerged as potential new treatment targets, as inhibitors of these proteins are currently under clinical investigation. This review gives a concise overview on the emerging clinical implications of mutations in the DDR genes in gastrointestinal cancers with a focus onBRCAmutations.
- Published
- 2021
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