Homologous Recombination Deficiency Scar: Mutations and Beyond-Implications for Precision Oncology.

Abstract

Simple SummaryA characteristic across several cancer types is a homologous recombination deficiency (HRD). HRD is associated with a better response to several anticancer therapies. Adequate assessment of HRD can therefore improve the outcome of such therapies. However, current methods to assess HRD are insufficient, leading to an underestimation of patients with HRD. This review discusses more accurate methods to detect HRD and how these can be applied for more personalized cancer treatment.Homologous recombination deficiency (HRD) is a prevalent in approximately 17% of tumors and is associated with enhanced sensitivity to anticancer therapies inducing double-strand DNA breaks. Accurate detection of HRD would therefore allow improved patient selection and outcome of conventional and targeted anticancer therapies. However, current clinical assessment of HRD mainly relies on determining germline BRCA1/2 mutational status and is insufficient for adequate patient stratification as mechanisms of HRD occurrence extend beyond functional BRCA1/2 loss. HRD, regardless of BRCA1/2 status, is associated with specific forms of genomic and mutational signatures termed HRD scar. Detection of this HRD scar might therefore be a more reliable biomarker for HRD. This review discusses and compares different methods of assessing HRD and HRD scar, their advances into the clinic, and their potential implications for precision oncology.