PARP Inhibitors in Colorectal Malignancies: A 2023 Update
Nikolaos Skouteris1, Georgios Papageorgiou2
1Division of Medical Oncology & Hematopoietic Cell Transplant Unit, Department of Medicine, "Metaxa" Cancer Hospital, 51 Botassi Street, 18537 Piraeus, Greece.
Background:
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.
Objective:
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.
Methods:
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.
Results:
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.
Conclusion:
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.
Insights
Poly (ADP-ribose) polymerase (PARP) inhibitors show promise for metastatic colorectal cancer (CRC) with DNA damage repair (DDR) alterations. Further research is needed to establish formal indications for these targeted therapies.
Area of Science:
- Oncology
- Medical Genetics
- Pharmacology
Background:
- Colorectal carcinoma (CRC) is a prevalent malignancy with poor prognosis in metastatic stages.
- DNA damage repair (DDR) pathway alterations are common in CRC, presenting a therapeutic vulnerability.
- Poly (ADP-ribose) polymerase (PARP) inhibitors exploit synthetic lethality in DDR-deficient cancers.
Purpose of the Study:
- To review the role of PARP inhibitors in metastatic CRC patients with DDR pathway alterations.
- To evaluate PARP inhibitors as a treatment option, alone or in combination therapies.
Main Methods:
- Systematic literature search of the PubMed database.
- Inclusion of human studies demonstrating PARP inhibitor efficacy in metastatic CRC with homologous repair deficiency (HRD).
Main Results:
- Current evidence suggests PARP inhibitors are beneficial in specific CRC subgroups.
- PARP inhibitors show potential as both monotherapy and in combination with other treatments.
Conclusions:
- Data are emerging to support PARP inhibitor use in select CRC patients.
- Further research is necessary to define formal indications and optimize treatment strategies.
- Identifying patients with homologous repair deficiency (HRD) is crucial for targeted therapy.
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