Genetic Polymorphisms as Treatment Biomarkers for Gynecological Malignancies Treated With Carboplatin and Paclitaxel: A Systematic Review.

Abstract

Purpose: Gynecological tumors, which correspond to the group of neoplasms that affect the female reproductive system, have high incidence and mortality rates. This systematic review aimed to summarize the most recent advances in identifying pharmacogenetic variants associated with the clinical outcomes of carboplatin-paclitaxel chemotherapy in these patients.

Methods: A comprehensive literature search was conducted across eight databases to identify studies published up to July 17, 2024. Two reviewers independently selected the studies and extracted the data; disagreements were resolved by two additional reviewers.

Findings: Out of the 2375 records that were found, only 20 met the eligibility criteria. The main findings were: (1) The three most extensively investigated genes were ATP binding cassette subfamily C member 1 (ABCB1), cytochrome P450 2C8 (CYP2C8), and glutathione S-transferase P1 (GSTP1); (2) three variants, rs1128503 (ABCB1), rs10509681 and rs11572080 (CYPC28), appear to have a significant association with important adverse drug reactions (in particular, neutropenia, thrombocytopenia, and peripheral sensory neuropathy). Others, as is the case with rs1045642 (ABCB1) and rs1695 (GSTP1), have inconsistent results, and the extent to which these results can be extrapolated is still limited; and (c) most of the included studies concerned Asian or European patients.

Implications: Therefore, future research should include more extensive analyses with more inclusive cohorts. As a limitation of the study, a meta-analysis was not possible due to the significant heterogeneity among the studies.