Therapeutic avenues for cancer neuroscience: translational frontiers and clinical opportunities

Diana D Shi; Jimmy A Guo; Hannah I Hoffman; Jennifer Su; Mari Mino-Kenudson; Jaimie L Barth; Jason M Schenkel; Jay S Loeffler; Helen A Shih; Theodore S Hong; Jennifer Y Wo; Andrew J Aguirre; Tyler Jacks; Lei Zheng; Patrick Y Wen; Timothy C Wang; William L Hwang

doi:10.1016/S1470-2045(21)00596-9

Therapeutic avenues for cancer neuroscience: translational frontiers and clinical opportunities

Lancet Oncol. 2022 Feb;23(2):e62-e74. doi: 10.1016/S1470-2045(21)00596-9.

Authors

Diana D Shi¹, Jimmy A Guo², Hannah I Hoffman³, Jennifer Su⁴, Mari Mino-Kenudson⁵, Jaimie L Barth⁵, Jason M Schenkel⁶, Jay S Loeffler⁷, Helen A Shih⁷, Theodore S Hong⁷, Jennifer Y Wo⁷, Andrew J Aguirre⁸, Tyler Jacks⁹, Lei Zheng¹⁰, Patrick Y Wen¹¹, Timothy C Wang¹², William L Hwang¹³

Affiliations

¹ Department of Radiation Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, MA, USA.
² Department of Radiation Oncology, Massachusetts General Hospital Cancer Center, Boston, MA, USA; School of Medicine, University of California, San Francisco, San Francisco, CA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Biological and Biomedical Sciences Program, Harvard University, Boston, MA, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
³ Department of Radiation Oncology, Massachusetts General Hospital Cancer Center, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Department of Biology, Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA; Harvard-MIT Health Sciences and Technology Program, Harvard Medical School, Boston, MA, USA.
⁴ Department of Radiation Oncology, Massachusetts General Hospital Cancer Center, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Department of Biology, Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
⁵ Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
⁶ Department of Biology, Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA; Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
⁷ Department of Radiation Oncology, Massachusetts General Hospital Cancer Center, Boston, MA, USA.
⁸ Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
⁹ Department of Biology, Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
¹⁰ Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
¹¹ Center for Neuro-Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
¹² Division of Digestive and Liver Diseases, Columbia University Medical Center, New York, NY, USA.
¹³ Department of Radiation Oncology, Massachusetts General Hospital Cancer Center, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Department of Biology, Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA. Electronic address: whwang1@mgh.harvard.edu.

Abstract

With increasing attention on the essential roles of the tumour microenvironment in recent years, the nervous system has emerged as a novel and crucial facilitator of cancer growth. In this Review, we describe the foundational, translational, and clinical advances illustrating how nerves contribute to tumour proliferation, stress adaptation, immunomodulation, metastasis, electrical hyperactivity and seizures, and neuropathic pain. Collectively, this expanding knowledge base reveals multiple therapeutic avenues for cancer neuroscience that warrant further exploration in clinical studies. We discuss the available clinical data, including ongoing trials investigating novel agents targeting the tumour-nerve axis, and the therapeutic potential for repurposing existing neuroactive drugs as an anti-cancer approach, particularly in combination with established treatment regimens. Lastly, we discuss the clinical challenges of these treatment strategies and highlight unanswered questions and future directions in the burgeoning field of cancer neuroscience.

Publication types

Review

MeSH terms

Cancer Pain / drug therapy
Clinical Trials as Topic
Drug Resistance, Neoplasm
Humans
Immune Checkpoint Inhibitors / therapeutic use
Neoplasms / drug therapy*
Neoplasms / etiology
Neoplasms / immunology
Neoplasms / pathology
Nervous System Physiological Phenomena / drug effects
Neurosciences*
Tumor Microenvironment

Substances

Immune Checkpoint Inhibitors

Abstract

Publication types

MeSH terms

Substances

Grants and funding