Cancer neuroscience: The past, the present, and the road ahead

# Cancer neuroscience: The past, the present, and the road ahead *Published: 2026 Apr 16* (2)Neurology Clinic, National Center for Tumor Diseases & European Center for Neurooncology (EZN), University Hospital Heidelberg, Heidelberg University, Heidelberg, Germany; Clinical Cooperation Unit Neurooncology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany. (3)Institute of Human Genetics, University Hospital Heidelberg, Heidelberg, Germany. (4)Division of Vascular Oncology and Metastasis, German Cancer Research Center (DKFZ), Heidelberg, Germany; Department of Vascular Biology and Tumor Angiogenesis, European Center for Angioscience (ECAS), Medical Faculty Mannheim, Heidelberg University, Heidelberg, Germany. (5)Department of Translational Genomics, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany; Department I of Internal Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany; Mildred Scheel School of Oncology Aachen Bonn Cologne Düsseldorf (MSSO ABCD), Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany. (6)Department of Surgery, TUM University Hospital, Technical University of Munich, Munich, Germany. (7)Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany. (8)Institute of Pharmacology, Heidelberg University, Heidelberg, Germany. (9)Department of Functional Neuroanatomy, Institute for Anatomy and Cell Biology, Heidelberg University, Heidelberg, Germany. (10)DKFZ-Hector Cancer Institute at the University Medical Center Mannheim, Mannheim, Germany; Department of Personalized Oncology, Mannheim University Medical Center, University of Heidelberg, Mannheim, Germany; Department of Personalized Medical Oncology (A420), German Cancer Research Center (DKFZ), German Center for Lung Research (DZL), Heidelberg, Germany. (11)DKFZ-Hector Cancer Institute at the University Medical Center Mannheim, Mannheim, Germany; Clinical Cooperation Unit Neuroimmunology and Brain Tumor Immunology, German Cancer Research Center (DKFZ), Heidelberg, Germany; German Cancer Consortium (DKTK), DKFZ, core center Heidelberg, Heidelberg, Germany; Department of Neurology, Medical Faculty Mannheim, Mannheim Center for Translation Neuroscience (MCTN), Heidelberg University, Mannheim, Germany; Helmholtz Institute for Translational Oncology Mainz (HI-TRON Mainz) - A Helmholtz Institute of the DKFZ, Mainz, Germany. (12)Department of Hematology and Stem Cell Transplantation, University Hospital Essen, Essen, Germany; West German Cancer Center, University Hospital Essen, Essen, Germany; DKTK Partner Site Essen/Düsseldorf, University Hospital Essen, Essen, Germany; Center for Molecular Biotechnology, University Hospital Essen, Essen, Germany. (13)Clinical Cooperation Unit Neurooncology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany. (14)Clinical Cooperation Unit Neuropathology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany; Department of Neuropathology, University Hospital Heidelberg, Heidelberg, Germany. (15)Paul-Flechsig-Institute, Centre for Neuropathology and Brain Research, Leipzig University, Leipzig, Germany. (16)Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), Heidelberg, Germany; Division of Stem Cells and Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany. (17)Neurology Clinic, National Center for Tumor Diseases & European Center for Neurooncology (EZN), University Hospital Heidelberg, Heidelberg University, Heidelberg, Germany; Clinical Cooperation Unit Neurooncology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany; German Cancer Consortium (DKTK), DKFZ, core center Heidelberg, Heidelberg, Germany. Both the nervous system and cancer-intrinsic neural features can govern cancer initiation, growth, progression, metastasis, and treatment resistance, while cancer can likewise influence the nervous system, promoting neural reprogramming and neuropsychiatric symptoms that worsen patient outcomes. The field of cancer neuroscience seeks to unravel this complex neuro-cancer crosstalk and holds the promise to develop neuroscience-instructed cancer therapies that improve disease control and quality of life. Here, we summarize the key discoveries of neuro-cancer crosstalk to date, including neuron-to-cancer synapses and paracrine and neuro-immuno-oncological interactions, and then explore emerging topics such as downstream effects on cancer cell pathophysiology, circadian influences, brain-body-cancer communication, and neural regulation of the metastatic cascade and the tumor microenvironment. Finally, we distill overarching principles, highlight relevant ongoing research, and outline conclusions to guide the development of cancer neuroscience, proposing hypotheses for future experimental validation. DOI: 10.1016/j.cell.2026.03.018