Overall, a multifaceted role of RPA mediated DNA damage repair through NER, DSB repair through HDR, DNA damage signaling/DDR, replication fork dynamics and its interaction with other proteins holds the potential to fine tune the pathway and it’s response to chemotherapy or radiotherapy induced DNA damage toward maximizing efficacy, overcoming resistance, and reducing the toxicities associated with existing cancer therapeutics. This evidence concerns the gene RPA1 and cancer.