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Genetic Polymorphisms as Treatment Biomarkers for Gynecological Malignancies Treated With Carboplatin and Paclitaxel:
Nadine de Godoy Torso1, Yasmim Gabriele Matos1, Giovana Fernanda Santos Fidelis1
1School of Medical Sciences, Universidade Estadual de Campinas, Campinas, Brazil.
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.
Insights
This review identifies pharmacogenetic variants linked to carboplatin-paclitaxel chemotherapy outcomes in gynecological cancers. Specific gene variants show associations with adverse drug reactions, though more research is needed.
Area of Science:
- Oncology
- Pharmacogenetics
- Gynecologic Oncology
Background:
- Gynecological tumors have high incidence and mortality rates.
- Carboplatin-paclitaxel chemotherapy is a common treatment for these cancers.
- Identifying genetic factors influencing treatment response is crucial for personalized medicine.
Purpose of the Study:
- To systematically review recent advances in pharmacogenetic variants associated with carboplatin-paclitaxel chemotherapy outcomes.
- To summarize findings on gene variants and their impact on clinical outcomes in gynecological cancer patients.
Main Methods:
- A comprehensive literature search was conducted across eight databases up to July 17, 2024.
- Two independent reviewers selected eligible studies and extracted data.
- Disagreements were resolved by two additional reviewers.
Main Results:
- Twenty studies were included from 2375 records.
- Key genes investigated include ABCB1, CYP2C8, and GSTP1.
- Variants rs1128503 (ABCB1), rs10509681, and rs11572080 (CYP2C8) are associated with adverse drug reactions like neutropenia and neuropathy.
- Other variants showed inconsistent results, limiting extrapolation.
- Most studies focused on Asian or European populations.
Conclusions:
- Future research requires more extensive analyses with inclusive cohorts.
- A meta-analysis was not feasible due to significant study heterogeneity.
- Further investigation is needed to validate findings and improve treatment strategies.
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