RAD51 mutations targeted treatment – pro
Human RAD51 is a homologue of the Escherichia coli RecA protein and is known to function in recombinational repair of double-stranded DNA breaks. Mutations in the lower eukaryotic homologues of RAD51 result in a deficiency in the repair of double-stranded DNA breaks. Loss of RAD51 function would therefore be expected to result in an elevated mutation rate, leading to accumulation of DNA damage and, hence, to increased cancer risk. RAD51 interacts directly or indirectly with a number of proteins implicated in breast cancer, such as BRCA1 and BRCA2.
Beyond case reports there is no literature to support the routine use of PARP inhibitors such as lynparza for the RAD51 family of mutations.
Lose F, Lovelock P, Chenevix-Trench G, Mann GJ, Pupo GM, Spurdle AB; Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer. Variation in the RAD51 gene and familial breast cancer. Breast Cancer Res. 2006;8(3):R26.
Le Calvez-Kelm F, Oliver J, Damiola F, Forey N, Robinot N, Durand G, Voegele C, Vallée MP, Byrnes G, Registry BC, Hopper JL, Southey MC, Andrulis IL, John EM, Tavtigian SV, Lesueur F. RAD51 and breast cancer susceptibility: no evidence for rare variant association in the Breast Cancer Family Registry study. PLoS One. 2012;7(12):e52374.
McKenzie K Grundy, Ronald J Buckanovich, Kara A Bernstein, Regulation and pharmacological targeting of RAD51 in cancer, NAR Cancer, Volume 2, Issue 3, September 2020, zcaa02
E, Chadran et ls, Significant Tumor Response to the Poly (ADP-ribose) Polymerase Inhibitor Olaparib in Heavily Pretreated Patient With Ovarian Carcinosarcoma Harboring a Germline RAD51D Mutation JCO Precision Oncology Volume 2, Number 2 Dec 12, 2018