Human cancer is a highly heterogeneous disease: more than 200 distinct types of human cancer have been described, and various tumor subtypes can be found within specific organs. It has been now accepted that it encompasses different cellular entities and a wide range of clinical behaviors, and is underpinned by a complex array of gene alterations. This phenotypic and genetic variability is what primarily determines the self‐progression of neoplastic disease and its response to therapy. Additionally, the asynchrony and self-progression of a cancer cell population suggests that the extent to which each neoplastic cell shares the properties of a non-tumoral cell may differ in time and in space. The complexity of alterations in cancer still presents a daunting problem with respect to treatment: how can we effectively treat cancers arising from such variability? A tumor consists of genetically distinct subpopulations of cancer cells, each with its own characteristic sensitivity profile to a given therapeutic agent. It has been proposed that each cancer therapy can be viewed as a “filter” that remove a portion of cancer cells that are sensitive to this treatment while allowing other insensitive subpopulations to escape. The need to tackle system complexity has become even more evident since completion of the various genome projects. One of the primary features of the living world is its tendency to form “multi-level” structures of "systems within systems", each of which forms a Whole in relation to its parts and is simultaneously part of a larger. An unsolved central question is how to transform molecular knowledge into an understanding of complex phenomena in cells, tissues, organs and organisms. In order to understand cancer as a complex system that involves so many interacting components, a critical analysis of traditional concepts is needed, as is reinterpretation of the clinical significance of failed therapies from the perspective of complexity. Two main concepts, multi-scale causality and heterogeneity need to be considered when generating new medical interventions. The need to find a new way of classifying tumoral entities, and objectively quantifying their morphological and functional changes, prompted us to investigate the theory of “complex systems”, and to apply their concepts to human cancer. This Research Topic is aimed at discussing molecular, cellular, clinical, epidemiological and imaging features that are fundamental for identifying the complexity underlying the onset and progression of human cancer. Analyzing cancer as a system that is complex in time and space might reveals more about its underlying behavioral characteristics. It is encouraging that clinicians, biologists and mathematicians contribute together towards a common understanding of cancer complexity. This multi-disciplinary view may help to clarify old concepts, categorize the actual knowledge, and suggest alternative approaches to discover new biomarkers with clinical and therapeutic value.
Guest Editor’s Profile
Dr. Fabio Grizzi graduated in Biological Sciences from the University of Milan in 1995 and, in the year, received the Steven Newburgh Annual Award for his contributions to the field of basic and applied biomedical research. In 2001, he was appointed Adjunct Assistant Professor at the Department of Internal Medicine and Hematology & Oncology at Texas Tech University Health Sciences Center in Lubbock, Texas, USA. In 2008, he was invited to become a Member of the National Cancer Institute-sponsored Pilot Cancer Antigen Prioritization Process, of the US National Institute of Health. In 2012, he was invited to become a Member of the worldwide validation of the “Immunoscore” on colon cancer. He is currently working as Chief of the Histology Laboratory at the Humanitas Research Hospital, Rozzano, Milan, Italy. In 2015 he was appointed Teacher at the Humanitas University, Faculty of Medicine for the course: "Building bodies: from gametes to organs, SSD BIO/17 Histology". He is Member of the Editorial Board of various scientific Journals and serves as Reviewer for prestigious Journals. He has published more than 180 peer-reviewed articles (H-index=31) and twenty-six book chapters, and made more than 300 presentations at national and international Congresses, and has recently been commissioned by Springer Publishing to prepare a book entitled “The Complexity of Cancer”, which will be published in 2019.
Submission deadline: July 15, 2019
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