HRness in Breast and Ovarian Cancers

• Published in: International journal of molecular sciences 2020-05, Vol.21 (11), p.3850
• Main Authors: Santana Dos Santos, Elizabeth, Lallemand, François, Petitalot, Ambre, Caputo, Sandrine M, Rouleau, Etienne
• Format: Article
• Language: English
• Subjects: Antineoplastic Agents - pharmacology; Apoptosis; Biomarkers, Tumor - genetics; BRCA1; BRCA1 protein; BRCA2; Breast; Breast cancer; breast cancer tumorigenesis; Breast carcinoma; Breast Neoplasms - genetics; Carcinogenesis; Cell Cycle; Cyclin-dependent kinases; Deoxyribonucleic acid; DNA; DNA Damage; DNA polymerase; DNA Repair; Epithelial cells; Estrogens; Female; Gene amplification; Gene expression; Genes, BRCA1; Genes, BRCA2; Genetic counseling; Genetic Predisposition to Disease; Genomes; Genomic instability; Germ-Line Mutation; Homologous Recombination; homologous recombination deficiency; Homology; Humans; Kinases; Mutation; Ovarian cancer; ovarian cancer tumorigenesis; Ovarian carcinoma; Ovarian Neoplasms - genetics; Phosphorylation; Proteins; Repair; Review; Tumorigenesis; Tumors
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms21113850

Ovarian and breast cancers are currently defined by the main pathways involved in the tumorigenesis. The majority are carcinomas, originating from epithelial cells that are in constant division and subjected to cyclical variations of the estrogen stimulus during the female hormonal cycle, therefore being vulnerable to DNA damage. A portion of breast and ovarian carcinomas arises in the context of DNA repair defects, in which genetic instability is the backdrop for cancer initiation and progression. For these tumors, DNA repair deficiency is now increasingly recognized as a target for therapeutics. In hereditary breast/ovarian cancers (HBOC), tumors with mutations present an impairment of DNA repair by homologous recombination (HR). For many years, mutations were only screened on germline DNA, but now they are also searched at the tumor level to personalize treatment. The reason of the inactivation of this pathway remains uncertain for most cases, even in the presence of a HR-deficient signature. Evidence indicates that identifying the mechanism of HR inactivation should improve both genetic counseling and therapeutic response, since they can be useful as new biomarkers of response.