Tumor Evolution: From Cells of Origin to Multifaceted Clonal Heterogeneity Supporting Malignant Progression

Tumor development occurs as a multistep process driven by the selection of accumulating variations. In 1990, Fearon and Vogelstein formulated a stepwise unifying model to describe tumor initiation and evolution, in which tumorigenesis and acquisition of malignant properties occur as the result of a defined sequence of genetic and epigenetic alterations. Indeed, oncogenic mutations can alter the homeostatic equilibrium of the cells in a given tissue and set the stage for the accumulation of further alterations associated with the progression of the disease. During the last three decades, this model has been tremendously complexified by an impressive amount of findings. Cancer development is currently known to be associated with the rise and dynamic evolution of multiple subclones that can co-exist as parts of a complex ecosystem. Additionally, cancer progression is supported by noncancerous cells, such as tumor-associated fibroblasts, immune cells, and by the microbiome that populates the tumor microenvironment. This heterogeneity controls the many-sided capacity of cancer cells to grow, disseminate, resist different treatments, escape immune response, and relapse. Understanding the bases of tumor evolution and heterogeneity represents one the greatest challenges in modern medicine and biomedical research.

In this Special Issue, we invite researchers to bridge the gap and tackle tumor evolution from different complementary angles, across a broad range of tumor types. We welcome review, research, and method manuscripts covering the areas of genetics and epigenetics of oncogenesis, invasion, resistance to treatments, as well as the role of the tumor microenvironment in these aspects.

Dr. Marco Bruschi
Dr. Francesco Baschieri
Dr. Salima Benbarche
Dr. Emmanuelle Sidot
Guest Editors

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