AUTHOR=Zimmer Kai , Kocher Florian , Puccini Alberto , Seeber Andreas 

TITLE=Targeting BRCA and DNA Damage Repair Genes in GI Cancers: Pathophysiology and Clinical Perspectives

JOURNAL=Frontiers in Oncology

VOLUME=11

YEAR=2021

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.662055

DOI=10.3389/fonc.2021.662055

ISSN=2234-943X

ABSTRACT=<p>Mutated germline alleles in the DNA damage repair (DDR) genes “breast cancer gene 1” (<italic>BRCA1</italic>) and <italic>BRCA2</italic> have 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 somatic <italic>BRCA</italic> mutations have been detected in several cancers. Since the approval of poly (ADP)-ribose polymerase inhibitors (PARPi) for <italic>BRCA-</italic>mutated cancers, <italic>BRCA</italic> mutations gained rising therapeutic implications. The impact and significance of <italic>BRCA</italic> mutations have been evaluated extensively in the last decades. Moreover, other genes involved in the DDR pathway, such as <italic>ATM</italic>, <italic>ATR</italic>, or <italic>CHK1</italic>, 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 on <italic>BRCA</italic> mutations.</p>