PARP Inhibitors in Colorectal Malignancies: A 2023 Update.

Abstract

Colorectal carcinoma (CRC) is one of the most common malignancies in the Western world, and metastatic disease is associated with a dismal prognosis. Poly-ADpribose polymerase (PARP) inhibitors gain increasing attention in the field of medical oncology, as they lead to synthetic lethality in malignancies with preexisting alterations in the DNA damage repair (DDR) pathway. As those alterations are frequently seen in CRC, a targeted approach through PARP inhibitors is expected to benefit these patients, both alone and in combination with other agents like chemotherapy, immunotherapy, antiangiogenics, and radiation. This review article aims to better clarify the role of PARP inhibitors as a treatment option in patients with metastatic CRC with alterations in the DDR pathway. We used the PubMed database to retrieve journal articles and the inclusion criteria were all human studies that illustrated the effective role of PARP inhibitors in patients with metastatic CRC with homologous repair deficiency (HRD) and the correct line of therapy. Current evidence supports the utilization of PARP inhibitors in CRC subgroups, as monotherapy and in combination with other agents. Up to now, data are insufficient to support a formal indication, and further research is needed. Efforts to precisely define the homologous repair deficiency (HRD) in CRC - and eventually the subgroup of patients that are expected to benefit the most - are also underway.