Gopalkumar Iyer, MD, presented “Role of DNA Repair Mutations in Sensitivity to Cisplatin-based Chemotherapy” at the 7th International Bladder Cancer Update on December 6, 2024, in Dallas, Texas.
How to cite: Iyer, Gopalkumar. “Role of DNA Repair Mutations in Sensitivity to Cisplatin-based Chemotherapy” December 2024. Accessed Mar 2025. https://grandroundsinurology.com/role-of-dna-repair-mutations-in-sensitivity-to-cisplatin-based-chemotherapy/
Role of DNA Repair Mutations in Sensitivity to Cisplatin-based Chemotherapy – Summary
Gopalkumar Iyer, MD, explores the role of genomic alterations in predicting response to neoadjuvant chemotherapy for muscle-invasive bladder cancer. In this 11-minute presentation, Dr. Iyer shares studies showing that pathologic downstaging at cystectomy significantly improves long-term survival. ERCC2 encodes a DNA helicase essential for repair, and its alterations lead to increased cisplatin sensitivity.
Dr. Iyer references the RETAIN-1 trial investigating a bladder-preserving approach based on DDR gene alterations. Further, secondary analyses of SWOG 1314 support DDR mutations as predictors of improved survival following neoadjuvant chemotherapy. Additional data suggest ERCC2 mutations may also enhance response to radiation and BCG therapy, potentially shaping future organ-preserving strategies. Comparisons between primary and secondary muscle-invasive bladder cancer reveal ERCC2 mutations predominantly in primary disease, supporting their role in tumor biology and treatment response.
Ongoing research evaluates whether DDR-targeted strategies can improve outcomes while reducing treatment intensity. Long-term follow-up remains crucial as bladder-preserving approaches gain traction, with further studies needed to confirm durability and oncologic safety.
About the 7th International Bladder Cancer Update:
The International Bladder Cancer Update (IBCU) is a CME conference focused on the diagnosis and treatment of bladder cancer. The conference offers medical professionals an opportunity to listen to updates from, and interact with, expert international faculty to improve knowledge and determine best treatment practices to improve patient outcomes. IBCU encompasses expert lectures, interactive discussions, a panel roundtable, debates, and case presentations. It is physician-led, multi-supported, and designed for urologists, urologic oncologists, and other healthcare professionals involved in the treatment of bladder cancer.
For further educational activities from this conference, visit our collection page.
ABOUT THE AUTHOR
Gopakumar Iyer, MD,earned his MD at Vanderbilt University Medical School, completed a residency in internal medicine at the University of Michigan as well as a fellowship in medical oncology at Memorial Sloan Kettering Cancer Center. Dr. Iyer iscurrently a genitourinary oncologist and early drug development specialist serving as the section head for bladder cancer at Memorial Sloan Kettering Cancer Center. Dr. Iyer isa member of Memorial Sloan Kettering’s Bladder Cancer Oncogenomics Project, a multidisciplinary effort to discover the key genetic abnormalities that drive this disease. He specializes in research in and treatment of patients with genitourinary cancers, including bladder, prostate, kidney, and testis cancers.
Dr. Iyer’s laboratory research focuses on defining the genetic aberrations that characterize bladder cancer, thereby identifying mutations that may serve as targets for novel therapies. Specifically, alterations within the PI3 kinase/Akt/mTOR pathway are commonly found in bladder cancer, and efforts to understand the biologic effects of pharmacologic inhibition of this pathway are underway. Loss of the TSC1 protein, a negative regulator of mTOR activation, has been shown to contribute to dramatic sensitivity of bladder tumors to everolimus therapy. He is working to elucidate the mechanisms underpinning drug sensitivity and defining the pattern of co-alterations with TSC1 loss in bladder cancer using next-generation sequencing techniques.
