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A Multimodal Approach to Discover Biomarkers for Taxane-Induced Peripheral Neuropathy (TIPN): A Study Protocol
Anukriti Sharma1, Ken B Johnson2, Bihua Bie3
1Department of Quantitative Health Sciences, 22516Lerner Research Institute, Cleveland Clinic, OH, USA.
Abstract:
Introduction: Taxanes are a class of chemotherapeutics commonly used to treat various solid tumors, including breast and ovarian cancers. Taxane-induced peripheral neuropathy (TIPN) occurs in up to 70% of patients, impacting quality of life both during and after treatment. TIPN typically manifests as tingling and numbness in the hands and feet and can cause irreversible loss of function of peripheral nerves. TIPN can be dose-limiting, potentially impacting clinical outcomes. The mechanisms underlying TIPN are poorly understood. As such, there are limited treatment options and no tools to provide early detection of those who will develop TIPN. Although some patients may have a genetic predisposition, genetic biomarkers have been inconsistent in predicting chemotherapy-induced peripheral neuropathy (CIPN). Moreover, other molecular markers (eg, metabolites, mRNA, miRNA, proteins) may be informative for predicting CIPN, but remain largely unexplored. We anticipate that combinations of multiple biomarkers will be required to consistently predict those who will develop TIPN. Methods: To address this clinical gap of identifying patients at risk of TIPN, we initiated the Genetics and Inflammatory Markers for CIPN (GENIE) study. This longitudinal multicenter observational study uses a novel, multimodal approach to evaluate genomic variation, metabolites, DNA methylation, gene expression, and circulating cytokines/chemokines prior to, during, and after taxane treatment in 400 patients with breast cancer. Molecular and patient reported data will be collected prior to, during, and after taxane therapy. Multi-modal data will be used to develop a set of comprehensive predictive biomarker signatures of TIPN. Conclusion: The goal of this study is to enable early detection of patients at risk of developing TIPN, provide a tool to modify taxane treatment to minimize morbidity from TIPN, and improved patient quality of life. Here we provide a brief review of the current state of research into CIPN and TIPN and introduce the GENIE study design.
Insights
This study introduces the GENIE study to identify biomarkers for predicting taxane-induced peripheral neuropathy (TIPN). Early detection aims to personalize cancer treatment and improve patient quality of life.
Area of Science:
- Oncology
- Neuroscience
- Pharmacology
Background:
- Taxanes are crucial chemotherapy drugs for solid tumors, but commonly cause peripheral neuropathy, impacting treatment and quality of life.
- Taxane-induced peripheral neuropathy (TIPN) affects up to 70% of patients, leading to sensory and motor deficits.
- Current methods for predicting TIPN are insufficient, with limited understanding of its underlying mechanisms and few treatment options.
Purpose of the Study:
- To address the clinical need for early detection of patients at risk for TIPN.
- To develop comprehensive predictive biomarker signatures for TIPN using a multimodal approach.
- To enable personalized taxane treatment adjustments, minimizing TIPN-related morbidity and enhancing patient quality of life.
Main Methods:
- The Genetics and Inflammatory Markers for CIPN (GENIE) study is a longitudinal, multicenter observational study.
- It involves 400 breast cancer patients undergoing taxane therapy.
- A multimodal approach collects data on genomic variation, metabolites, DNA methylation, gene expression, and cytokines/chemokines before, during, and after treatment.
Main Results:
- This study is designed to identify comprehensive predictive biomarker signatures for TIPN.
- Analysis of multimodal data will correlate molecular profiles with TIPN development.
- Patient-reported outcomes will be integrated with molecular data to understand the patient experience of TIPN.
Conclusions:
- The GENIE study aims to provide a novel tool for early TIPN risk assessment.
- Findings will support modifications in taxane treatment strategies to mitigate neuropathy.
- The ultimate goal is to improve the quality of life for cancer patients undergoing taxane chemotherapy.
