A Multimodal Approach to Discover Biomarkers for Taxane-Induced Peripheral Neuropathy (TIPN): A Study Protocol

Author:

Sharma Anukriti1,Johnson Ken B.2,Bie Bihua3,Rhoades Emily E.4,Sen Alper2,Kida Yuri2,Hockings Jennifer567,Gatta Alycia4,Davenport Jacqueline4,Arcangelini Connie4,Ritzu Jennifer4,DeVecchio Jennifer5,Hughen Ron2,Wei Mei8,Thomas Budd G.479,Lynn Henry N.10ORCID,Eng Charis457119,Foss Joseph3,Rotroff Daniel M.17912ORCID

Affiliation:

1. Department of Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic, OH, USA

2. Department of Anesthesiology, University of Utah, UT, USA

3. Department of Anesthesiology, Cleveland Clinic, OH, USA

4. Taussig Cancer Institute, Cleveland Clinic, OH, USA

5. Genomic Medicine Institute, Lerner Research Institute, Cleveland Clinic, OH, USA

6. Department of Pharmacy, Cleveland Clinic, OH, USA

7. Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Cleveland, OH, USA

8. Huntsman Cancer Institute, University of Utah, Salt Lake City, UT

9. Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, OH, USA

10. University of Michigan Rogel Cancer Center, Ann Arbor, MI, USA

11. Department of Genetics and Genome Sciences, Case Western Reserve University School of Medicine, Cleveland, OH, USA

12. Endocrinology and Metabolism Institute, Cleveland Clinic, Cleveland, 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.

Funder

National Institute of Neurological Disorders and Stroke

Publisher

SAGE Publications

Subject

Cancer Research,Oncology

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