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Updated: Jul 16, 2025
Trans-Tympanic Drug Delivery for the Treatment of Ototoxicity
Published on: March 16, 2018
Systematic Critical Review of Genetic Factors Associated with Cisplatin-induced Ototoxicity: Canadian
Erika N Scott1,2, Akshaya A Joseph1,3, Angie Dhanda1,3
1BC Children's Hospital Research Institute, Vancouver, British Columbia, Canada.
Background:
Cisplatin is commonly used to treat solid tumors; however, its use can be complicated by drug-induced hearing loss (ie, ototoxicity). The presence of certain genetic variants has been associated with the development/occurrence of cisplatin-induced ototoxicity, suggesting that genetic factors may be able to predict patients who are more likely to develop ototoxicity. The authors aimed to review genetic associations with cisplatin-induced ototoxicity and discuss their clinical relevance.
Methods:
An updated systematic review was conducted on behalf of the Canadian Pharmacogenomics Network for Drug Safety, based on the Preferred Reporting Items for Systematic reviews and Meta-Analyses 2020 statement. Pharmacogenomic studies that reported associations between genetic variation and cisplatin-induced ototoxicity were included. The evidence on genetic associations was summarized and evaluated, and knowledge gaps that can be used to inform future pharmacogenomic studies identified.
Results:
Overall, 40 evaluated reports, considering 47 independent patient populations, captured associations involving 24 genes. Considering GRADE criteria, genetic variants in 2 genes were strongly (ie, odds ratios ≥3) and consistently (ie, replication in ≥3 independent populations) predictive of cisplatin-induced ototoxicity. Specifically, an ACYP2 variant has been associated with ototoxicity in both children and adults, whereas TPMT variants are relevant in children. Encouraging evidence for associations involving several other genes also exists; however, further research is necessary to determine potential clinical relevance.
Conclusions:
Genetic variation in ACYP2 and TPMT may be helpful in predicting patients at the highest risk of developing cisplatin-induced ototoxicity. Further research (including replication studies considering diverse pediatric and adult patient populations) is required to determine whether genetic variation in additional genes may help further identify patients most at risk.
Insights
Genetic variants in ACYP2 and TPMT show promise for predicting cisplatin-induced ototoxicity. Further research is needed to confirm these findings and explore other genetic factors for personalized cancer treatment.
Area of Science:
- Pharmacogenomics
- Oncology
- Genetics
Background:
- Cisplatin is a vital chemotherapy drug for solid tumors.
- Cisplatin-induced ototoxicity (hearing loss) is a significant clinical challenge.
- Genetic factors may predict susceptibility to cisplatin ototoxicity.
Approach:
- Systematic review of pharmacogenomic studies.
- Evaluation of genetic associations with cisplatin-induced ototoxicity.
- Adherence to Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) 2020 guidelines.
Key Points:
- 40 reports and 47 patient populations were analyzed, involving 24 genes.
- Genetic variants in ACYP2 and TPMT strongly predict ototoxicity in children and adults.
- ACYP2 variants are linked to ototoxicity in both pediatric and adult populations.
Conclusions:
- ACYP2 and TPMT genetic variations can help identify patients at high risk for cisplatin ototoxicity.
- Further research is necessary to validate these findings and explore additional genetic predictors.
- Replication studies in diverse populations are crucial for clinical application.
