Unveiling Chemoresistance: New Insights from BRCA2 Research

According to a new study, the MMS22L-TONSL complex and FIGNL1-modulated RAD51 can restore homologous recombination and enable chemoresistance in BRCA2-deficient tumors.

BRCA2 loss was classically linked to homologous recombination (HR) deficiency and predictable sensitivity to PARP inhibitors and DNA-damaging chemotherapy. The new data add nuance to that model: when compensatory factors engage, HR can be functionally restored in the absence of BRCA2.

Removal or inhibition of FIGNL1 allowed RAD51 to remain bound to damaged DNA, restoring RAD51 loading/stability and measurable HR activity in BRCA2-deficient models.

Targeting MMS22L-TONSL or modulating FIGNL1 therefore presents a rational strategy to resensitize HR-restored, BRCA2-mutant tumors. Early translational steps will prioritize selective inhibitor development or genetic target validation with robust target-engagement biomarkers.