Neurobiology of Cancer

Boris Mravec was born in 1975 in Slovakia. In 2000 he graduated from the Faculty of Medicine of Comenius University in Bratislava. Subsequently, as part of his PhD studies at the Slovak Academy of Sciences under the supervision of RNDr. Richard Kvetnanský, DSc., was devoted to the research of central regulation of neuroendocrine stress response in the rat. During his PhD studies he completed several study visits in the laboratory of prof. MD. Miklos Palkovits, DSc., during which, among other things, he learned the method of rat and mouse brain microdissection. After defending his PhD degree in 2005, he joined the Institute of Pathological Physiology as a lecturer first and since 2014 he has been working at the Institute of Physiology, Faculty of Medicine, Comenius University. At the same time, he also works as a researcher at the Biomedical Centre of the Slovak Academy of Sciences.

            Since 2005, together with his colleagues and PhD students, he has been researching the role of the nervous system in the tumor process in peripheral tissues. During this period, several publications related to this area of research were available. However, these papers mostly focused only on some aspects of the relationship between the nervous system and tumor. Most of the papers focused on investigating and describing the influence of the nervous system on the tumor; only a small number of papers dealt with the influence of the tumor on the nervous system. Thus, a more comprehensive and unifying concept describing the bidirectional relationships between the nervous system and tumor tissue was lacking. Therefore, in 2008, he and his colleagues published a comprehensive description of the role of the nervous system in cancer and introduced the term "cancer neurobiology" to the literature.

            As he specialized in the study of brain structures regulating the neuroendocrine stress response as part of his PhD studies, the main goal of his further research activities was to elucidate, at least in part, the mechanisms mediating the adverse effects of stress on tumor initiation and progression in laboratory animals using approaches such as exposing animals to stressors, eliminating sympathetic nerve endings with the neurotoxin 6-hydroxydopamine, or decreasing adrenergic signaling by using the beta-blocker propranolol. Later, he also focused on the role of the parasympathetic nervous system when, in the framework of an international project led by Prof. Yori Gidron, he investigated the effect of chronic stimulation of the nervus vagus on the development of fibrosarcoma in rats. In addition, as tumor growth may also represent a specific stressor, he and his colleagues also focused on investigating changes in the activity of selected brain structures in animals with tumors growing in peripheral tissues. In addition to describing changes in brain activity in animals during tumor progression in different compartments of the body (e.g., intraperitoneally and subcutaneously), they also described the effect of tumor on brain structures involved in the regulation of various processes in the brain and periphery. Recently, the focus has been on validating the mechanisms of neuro-tumor interactions in clinical trials and on the application of the knowledge gained in the treatment of cancer patients.

Introduction.- I: The concept of neurobiology of cancer.- Definition of cancer neurobiology.- History of research on the role of the nervous system in cancer.- II: Basic pillars of cancer neurobiology.- Psychosocial factors influence the development and progression of cancer.- Tumor tissue is innervated.- Neurotransmitters influence the development and progression of cancer.- Neuro-endocrine-immune network complexly modulates the tumor process.- Changes in signal transduction between the nervous system and peripheral tissue influence the development and progression of cancer.- Tumor tissue affects the activity of the nervous system.- Summary.- III: Influence of the nervous system on features of cancer.- Genome instability and mutation.- Tumor-promoting inflammation.- Avoiding immune destruction.- Sustaining proliferative signalling.- Resisting cell death.- Deregulating cellular metabolism.- Inducting or accessing vasculature.- Activating invasion and metastasis.- Enabling replicative immortality.- Nonmutational epigenetic reprogramming.- Evading growth suppressors.- Unlocking phenotypic plasticity.- Senescent cells.- Polymorphic microbiomes.- Summary.- IV: Homeostasis, allostasis and cancer.- The concept of homeostasis.- Three basic levels of homeostatic regulation.- The concept of allostasis.- Disruption of homeostasis in cancer.- Summary.- V: Stress and cancer.- Stress reaction.- Mechanisms mediating the effect of stress on the tumor process.- Sources of stress in cancer patients.- Stress and cancer: mechanisms.- Stress as a contributing factor in cancer.- Stress as a factor stimulating cancer progression, metastasis and increasing cancer mortality.- Summary.- VI: The role of the nervous system in selected cancers.- Breast cancer.- Lung cancer.- Melanoma.- Prostate cancer.- Pancreatic cancer.- Stomach cancer.- Colorectal cancer.- Head and neck cancer.- Cervical cancer.- Uterine cancer.- Ovarian cancer.- Hepatocellular carcinoma.- Leukemias.- Multiple myeloma.- Other cancers.- Metastasis.- Summary.- VII: Therapeutic and preventive implications of cancer neurobiology.- Reducing the negative effects of stress.- Influencing the efficacy of anticancer treatments.- Influencing late sequelae of anti-cancer treatment.- Procedures increasing the activity of the parasympathetic nervous system.- Limiting the effects of the tumor on the brain.- The use of classical conditioning in the treatment of cancer.- The influence of hypnosis and suggestion.- Summary.- VIII: Future directions of research in cancer neurobiology.- The role of adrenergic signaling in cancer.- The role of the hypothalamic-pituitary-adrenal axis in the development and progression of cancer.- Eustress and exercise.- The role of the parasympathetic nervous system in carcinogenesis and cancer progression.- Impact of chemotherapy-induced neuropathy on cancer progression.- Experimental and clinical research.- Summary.- IX: Conclusion.