Principal Investigator

Awardee Organization

University Of Rochester
United States

Fiscal Year
Activity Code
Early Stage Investigator Grants (ESI)
Not Applicable
Project End Date

Assessing the role of the interoceptive brain system in the pathophysiology and treatment of chemotherapy-induced peripheral neuropathy

Chemotherapy-induced peripheral neuropathy (CIPN) is a severe dose-limiting toxicity that affects over 65% of the roughly 250,000 patients per year receiving neurotoxic chemotherapy (e.g., taxane-, platinum-, vinca alkaloid-based), which is widely used for breast, prostate, lung, colorectal, and blood cancers among others. Not only does CIPN increase mortality by limiting the dose of chemotherapy, CIPN affects walking, writing, eating, and dressing via numbness, tingling, pain, cold sensitivity, and cramping in the hands and feet. There are no FDA-approved treatments for CIPN because we need a greater understanding of the pathophysiology of CIPN and mechanisms of action of promising treatments for CIPN. To date, most research on CIPN pathophysiology has focused on peripheral sensory nerve damage. This project is motivated by an innovative perspective that CIPN symptoms are not due simply to peripheral nerve damage, but rather that CIPN symptoms are worsened by damage to the interoceptive brain system (i.e., the brain’s reaction to peripheral nerve damage). The long-term vision for this project is mechanism-based CIPN sub-typing and mechanismbased treatments for CIPN informed by brain fMRI, as has been done in other brain-mediated conditions such as chronic pain and depression. This is a Phase II randomized clinical trial to assess CIPN and fMRI brain connectivity in the interoceptive brain system in 66 patients with CIPN from neurotoxic chemotherapy before and after 6 weeks of exercise vs. usual care. This study will be included as part of the clinical trial URCC 19075. The specific aims of this project are (1) to obtain preliminary estimates of the relationships between CIPN and functional connectivity in the interoceptive brain system in patients with CIPN, and (2) to obtain preliminary estimates of the effects of exercise vs. no exercise on both CIPN severity and functional connectivity in the interoceptive brain system in patients with CIPN. This is the first study to examine the interoceptive brain system in the pathophysiology and treatment of CIPN. Results from this study will inform an R01 application to more definitively assess this theory of CIPN and exercise. If this work is successful, it will reveal a novel objective biomarker of CIPN—functional connectivity in the interoceptive brain system—to improve prediction, tracking, sub-typing, and treatment of CIPN using exercise or other interventions that affect this brain system. This will ultimately help alleviate the burden of chemotherapy on treating patients with cancer. Chair: Ian Kleckner


  • Chung KH, Park SB, Streckmann F, Wiskemann J, Mohile N, Kleckner AS, Colloca L, Dorsey SG, Kleckner IR. Mechanisms, Mediators, and Moderators of the Effects of Exercise on Chemotherapy-Induced Peripheral Neuropathy. Cancers. 2022 Feb 26;14. (5). PMID: 35267533
  • Park SB, Tamburin S, Schenone A, Kleckner IR, Velasco R, Alberti P, Kanzawa-Lee G, Lustberg M, Dorsey SG, Mantovani E, Hamedani M, Argyriou AA, Cavaletti G, Hoke A, Toxic Neuropathy Consortium. Optimal outcome measures for assessing exercise and rehabilitation approaches in chemotherapy-induced peripheral-neurotoxicity: Systematic review and consensus expert opinion. Expert review of neurotherapeutics. 2022 Jan;22(1):65-76. Epub 2022 Jan 11. PMID: 34894974
  • Tamburin S, Park SB, Schenone A, Mantovani E, Hamedani M, Alberti P, Yildiz-Kabak V, Kleckner IR, Kolb N, Mazzucchelli M, McNeish BL, Argyriou AA, Cavaletti G, Hoke A, Toxic Neuropathy Consortium. Rehabilitation, exercise, and related non-pharmacological interventions for chemotherapy-induced peripheral neurotoxicity: Systematic review and evidence-based recommendations. Critical reviews in oncology/hematology. 2022 Mar;171:103575. Epub 2021 Dec 28. PMID: 34968623