Roadmap for the Emerging Field of Cancer Neuroscience

doi:10.1016/j.cell.2020.03.034

. 2020 Apr 16;181(2):219-222.

doi: 10.1016/j.cell.2020.03.034.

Roadmap for the Emerging Field of Cancer Neuroscience

Michelle Monje¹, Jeremy C Borniger², Nisha J D'Silva³, Benjamin Deneen⁴, Peter B Dirks⁵, Faranak Fattahi⁶, Paul S Frenette⁷, Livia Garzia⁸, David H Gutmann⁹, Douglas Hanahan¹⁰, Shawn L Hervey-Jumper¹¹, Hubert Hondermarck¹², Jonathan B Hurov¹³, Adam Kepecs², Sarah M Knox¹⁴, Alison C Lloyd¹⁵, Claire Magnon¹⁶, Jami L Saloman¹⁷, Rosalind A Segal¹⁸, Erica K Sloan¹⁹, Xin Sun²⁰, Michael D Taylor²¹, Kevin J Tracey²², Lloyd C Trotman², David A Tuveson², Timothy C Wang²³, Ruth A White²⁴, Frank Winkler²⁵

Affiliations

¹ Departments of Neurology & Neurological Sciences, Pediatrics, Pathology, Neurosurgery, and Psychiatry & Behavioral Sciences, Stanford University, Stanford, CA 94305, USA. Electronic address: mmonje@stanford.edu.
² Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
³ Department of Periodontics and Oral Medicine, School of Dentistry, Department of Pathology, School of Medicine, University of Michigan, Ann Arbor, MI 48109, USA.
⁴ Center for Cell and Gene Therapy, Department of Neurosurgery, Baylor College of Medicine, Houston, TX 77030, USA.
⁵ Division of Neurosurgery, Arthur and Sonia Labatt Brain Tumor Research Center, Departments of Surgery and Molecular Genetics, Hospital for Sick Children, Toronto, ON M5G1X8, Canada.
⁶ Department of Biochemistry and Biophysics, Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA 94115, USA.
⁷ Departments of Medicine and Cell Biology, Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
⁸ Cancer Research Program, Research Institute of the McGill University Health Center and Department of Surgery, McGill University, Montreal, QC, Canada.
⁹ Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110, USA.
¹⁰ Swiss Institute for Experimental Cancer Research, Swiss Federal Institute of Technology Lausanne, Ludwig Institute for Cancer Research, Swiss Cancer Center Leman, Lausanne, Switzerland.
¹¹ Department of Neurosurgery, University of California, San Francisco, San Francisco, CA 94115, USA.
¹² School of Biomedical Sciences and Pharmacy, Hunter Medical Research Institute, University of Newcastle, Callaghan, NSW 2308, Australia.
¹³ Cygnal Therapeutics, Cambridge, MA 02139, USA.
¹⁴ Program in Craniofacial Biology, Department of Cell and Tissue Biology, University of California, San Francisco, San Francisco, CA 94143, USA.
¹⁵ MRC Laboratory for Molecular Cell Biology, University College London, London WC1E 6BT, UK.
¹⁶ UMR1274 (Equipe Cancer et Microenvironnement-INSERM-CEA), Institut de Radiobiologie Cellulaire et Moléculaire, Institut de Biologie François Jacob, Direction de la Recherche Fondamentale, Paris, France.
¹⁷ Departments of Medicine and Neurobiology, University of Pittsburgh, Pittsburgh, PA 15260, USA.
¹⁸ Department of Neurobiology, Harvard Medical School and Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
¹⁹ Monash Institute of Pharmaceutical Sciences, Monash University, Melbourne, VIC 3052, Australia.
²⁰ Departments of Pediatrics and Biological Sciences, University of California at San Diego, La Jolla, CA 92093, USA.
²¹ Division of Neurosurgery, Arthur and Sonia Labatt Brain Tumor Research Center, Developmental and Stem Cell Biology Program, Departments of Surgery, Laboratory Medicine & Pathology and Medical Biophysics, Hospital for Sick Children, Toronto, ON M5G1X8, Canada.
²² The Feinstein Institute for Medical Research, Northwell Health, Manhasset, NY 11030, USA.
²³ Division of Digestive and Liver Diseases, Department of Medicine, Columbia University Irving Medical Center, New York, NY 10032, USA.
²⁴ Division of Hematology and Oncology, Department of Medicine, Columbia University Irving Medical Center, New York, NY 10032, USA.
²⁵ Neurology Clinic and National Center for Tumor Diseases, University Hospital Heidelberg, DKTK & Clinical Cooperation Unit Neurooncology, German Cancer Research Center, Heidelberg, Germany.

PMID: 32302564
PMCID: PMC7286095
DOI: 10.1016/j.cell.2020.03.034

Roadmap for the Emerging Field of Cancer Neuroscience

Michelle Monje et al. Cell. 2020.

. 2020 Apr 16;181(2):219-222.

doi: 10.1016/j.cell.2020.03.034.

Authors

Affiliations

¹ Departments of Neurology & Neurological Sciences, Pediatrics, Pathology, Neurosurgery, and Psychiatry & Behavioral Sciences, Stanford University, Stanford, CA 94305, USA. Electronic address: mmonje@stanford.edu.
² Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
³ Department of Periodontics and Oral Medicine, School of Dentistry, Department of Pathology, School of Medicine, University of Michigan, Ann Arbor, MI 48109, USA.
⁴ Center for Cell and Gene Therapy, Department of Neurosurgery, Baylor College of Medicine, Houston, TX 77030, USA.
⁵ Division of Neurosurgery, Arthur and Sonia Labatt Brain Tumor Research Center, Departments of Surgery and Molecular Genetics, Hospital for Sick Children, Toronto, ON M5G1X8, Canada.
⁶ Department of Biochemistry and Biophysics, Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA 94115, USA.
⁷ Departments of Medicine and Cell Biology, Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
⁸ Cancer Research Program, Research Institute of the McGill University Health Center and Department of Surgery, McGill University, Montreal, QC, Canada.
⁹ Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110, USA.
¹⁰ Swiss Institute for Experimental Cancer Research, Swiss Federal Institute of Technology Lausanne, Ludwig Institute for Cancer Research, Swiss Cancer Center Leman, Lausanne, Switzerland.
¹¹ Department of Neurosurgery, University of California, San Francisco, San Francisco, CA 94115, USA.
¹² School of Biomedical Sciences and Pharmacy, Hunter Medical Research Institute, University of Newcastle, Callaghan, NSW 2308, Australia.
¹³ Cygnal Therapeutics, Cambridge, MA 02139, USA.
¹⁴ Program in Craniofacial Biology, Department of Cell and Tissue Biology, University of California, San Francisco, San Francisco, CA 94143, USA.
¹⁵ MRC Laboratory for Molecular Cell Biology, University College London, London WC1E 6BT, UK.
¹⁶ UMR1274 (Equipe Cancer et Microenvironnement-INSERM-CEA), Institut de Radiobiologie Cellulaire et Moléculaire, Institut de Biologie François Jacob, Direction de la Recherche Fondamentale, Paris, France.
¹⁷ Departments of Medicine and Neurobiology, University of Pittsburgh, Pittsburgh, PA 15260, USA.
¹⁸ Department of Neurobiology, Harvard Medical School and Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
¹⁹ Monash Institute of Pharmaceutical Sciences, Monash University, Melbourne, VIC 3052, Australia.
²⁰ Departments of Pediatrics and Biological Sciences, University of California at San Diego, La Jolla, CA 92093, USA.
²¹ Division of Neurosurgery, Arthur and Sonia Labatt Brain Tumor Research Center, Developmental and Stem Cell Biology Program, Departments of Surgery, Laboratory Medicine & Pathology and Medical Biophysics, Hospital for Sick Children, Toronto, ON M5G1X8, Canada.
²² The Feinstein Institute for Medical Research, Northwell Health, Manhasset, NY 11030, USA.
²³ Division of Digestive and Liver Diseases, Department of Medicine, Columbia University Irving Medical Center, New York, NY 10032, USA.
²⁴ Division of Hematology and Oncology, Department of Medicine, Columbia University Irving Medical Center, New York, NY 10032, USA.
²⁵ Neurology Clinic and National Center for Tumor Diseases, University Hospital Heidelberg, DKTK & Clinical Cooperation Unit Neurooncology, German Cancer Research Center, Heidelberg, Germany.

PMID: 32302564
PMCID: PMC7286095
DOI: 10.1016/j.cell.2020.03.034

Abstract

Mounting evidence indicates that the nervous system plays a central role in cancer pathogenesis. In turn, cancers and cancer therapies can alter nervous system form and function. This Commentary seeks to describe the burgeoning field of "cancer neuroscience" and encourage multidisciplinary collaboration for the study of cancer-nervous system interactions.

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Conflict of interest statement

Declaration of Interests M.M., P.S.F., T.C.W, H.H., E.K.S. and D.A.T. are on the SAB for Cygnal Therapeutics. J.B.H. is an employee of Cygnal Therapeutics. F.W. is co-founder of Divide & Conquer (DC Europa Ltd).

Figures

None — **Interactions between the nervous system and cancer.**
A) Synaptic communication between neurons and brain cancer cells (e.g. malignant glioma, red) can regulate cancer growth through neurotransmitter and voltage-regulated mechanisms. Whether synaptic interactions occur between peripheral nervous system axons and cancer cells outside of the central nervous system remains to be explored. B) Paracrine signaling between neurons/nerves (grey) and cancer cells (red), for example neuronal activity-dependent release of neurotransmitters or growth factors, regulates cancer growth in a wide range of tissues. The influence of neurons on malignant cells may be direct or may be mediated through effects on other cell types (green) in the tumor microenvironment. Cancer-derived paracrine factors remodel the nervous system to promote increased neural activity in the tumor microenvironment. C) Circulating factors from cancer (red) can influence nervous system (grey) functions such as sleep, while the nervous system can influence cancer progression through circulating factors such as hormones and progenitor cells or through altered immune system (blue) function. D) Cancer therapies frequently cause nervous system toxicities, from peripheral neuropathy to cognitive impairment. Molecular and cellular mechanisms of nervous system toxicities and the putative role that such disruption in nervous system function may play in cancer treatment efficacy require further study.

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References

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1. Borovikova LV, Ivanova S, Zhang M, Yang H, Botchkina GI, Watkins LR, Wang H, Abumrad N, Eaton JW, and Tracey KJ (2000). Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin. Nature 405, 458–462. - PubMed
1. Gibson EM, Nagaraja S, Ocampo A, Tam LT, Wood LS, Pallegar PN, Greene JJ, Geraghty AC, Goldstein AK, Ni L, et al. (2019). Methotrexate Chemotherapy Induces Persistent Tri-glial Dysregulation that Underlies Chemotherapy-Related Cognitive Impairment. Cell 176, 43–55 e13. - PMC - PubMed
1. Gibson EM, Purger D, Mount CW, Goldstein AK, Lin GL, Wood LS, Inema I, Miller SE, Bieri G, Zuchero JB, et al. (2014). Neuronal activity promotes oligodendrogenesis and adaptive myelination in the mammalian brain. Science 344, 1252304. - PMC - PubMed
1. Hayakawa Y, Sakitani K, Konishi M, Asfaha S, Niikura R, Tomita H, Renz BW, Tailor Y, Macchini M, Middelhoff M, et al. (2017). Nerve Growth Factor Promotes Gastric Tumorigenesis through Aberrant Cholinergic Signaling. Cancer Cell 31, 21–34. - PMC - PubMed

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[1] Borniger JC, Walker Ii WH, Surbhi, Emmer KM, Zhang N, Zalenski AA, Muscarella SL, Fitzgerald JA, Smith AN, Braam CJ, et al. (2018). A Role for Hypocretin/Orexin in Metabolic and Sleep Abnormalities in a Mouse Model of Non-metastatic Breast Cancer. Cell Metab 28, 118–129 e115. - PMC - PubMed

[2] Borniger JC, Walker Ii WH, Surbhi, Emmer KM, Zhang N, Zalenski AA, Muscarella SL, Fitzgerald JA, Smith AN, Braam CJ, et al. (2018). A Role for Hypocretin/Orexin in Metabolic and Sleep Abnormalities in a Mouse Model of Non-metastatic Breast Cancer. Cell Metab 28, 118–129 e115. - PMC - PubMed

[3] Borovikova LV, Ivanova S, Zhang M, Yang H, Botchkina GI, Watkins LR, Wang H, Abumrad N, Eaton JW, and Tracey KJ (2000). Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin. Nature 405, 458–462. - PubMed

[4] Borovikova LV, Ivanova S, Zhang M, Yang H, Botchkina GI, Watkins LR, Wang H, Abumrad N, Eaton JW, and Tracey KJ (2000). Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin. Nature 405, 458–462. - PubMed

[5] Gibson EM, Nagaraja S, Ocampo A, Tam LT, Wood LS, Pallegar PN, Greene JJ, Geraghty AC, Goldstein AK, Ni L, et al. (2019). Methotrexate Chemotherapy Induces Persistent Tri-glial Dysregulation that Underlies Chemotherapy-Related Cognitive Impairment. Cell 176, 43–55 e13. - PMC - PubMed

[6] Gibson EM, Nagaraja S, Ocampo A, Tam LT, Wood LS, Pallegar PN, Greene JJ, Geraghty AC, Goldstein AK, Ni L, et al. (2019). Methotrexate Chemotherapy Induces Persistent Tri-glial Dysregulation that Underlies Chemotherapy-Related Cognitive Impairment. Cell 176, 43–55 e13. - PMC - PubMed

[7] Gibson EM, Purger D, Mount CW, Goldstein AK, Lin GL, Wood LS, Inema I, Miller SE, Bieri G, Zuchero JB, et al. (2014). Neuronal activity promotes oligodendrogenesis and adaptive myelination in the mammalian brain. Science 344, 1252304. - PMC - PubMed

[8] Gibson EM, Purger D, Mount CW, Goldstein AK, Lin GL, Wood LS, Inema I, Miller SE, Bieri G, Zuchero JB, et al. (2014). Neuronal activity promotes oligodendrogenesis and adaptive myelination in the mammalian brain. Science 344, 1252304. - PMC - PubMed

[9] Hayakawa Y, Sakitani K, Konishi M, Asfaha S, Niikura R, Tomita H, Renz BW, Tailor Y, Macchini M, Middelhoff M, et al. (2017). Nerve Growth Factor Promotes Gastric Tumorigenesis through Aberrant Cholinergic Signaling. Cancer Cell 31, 21–34. - PMC - PubMed

[10] Hayakawa Y, Sakitani K, Konishi M, Asfaha S, Niikura R, Tomita H, Renz BW, Tailor Y, Macchini M, Middelhoff M, et al. (2017). Nerve Growth Factor Promotes Gastric Tumorigenesis through Aberrant Cholinergic Signaling. Cancer Cell 31, 21–34. - PMC - PubMed

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Roadmap for the Emerging Field of Cancer Neuroscience

Affiliations

Roadmap for the Emerging Field of Cancer Neuroscience

Authors

Affiliations

Abstract

Conflict of interest statement

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