Tumor Biology and Natural History

Tumors are not uniform diseases but heterogeneous entities consisting of cell populations called cell clones, with different genetic and molecular features. The ability of a tumor to evolve and fit to host microenvironment, by developing often resistance mechanisms to the anticancer therapies, is dependent on this biological variability. In fact, the variability observed within individual tumors, known as intra-tumor heterogeneity, represents the crucial step in cancer clonal evolution process, by promoting and driving a genetic mechanism able to select the fittest cell clones. A single clonal origin is usually shown by most of tumors at the early stages of the disease, whereas advanced-stage tumors may contain multiple cell populations with different characteristics.Knowing thoroughly the evolutionary history of a tumor along the space-time axis is an essential factor for developing new screening strategies able to early identify neoplasm when genetic variability is low and the disease is evolving. The implementation of more specific and sensitive clinical approaches is needed, due to the correlations observed between clinical outcome and tumor diversity, in order to better characterize and evaluate tumor heterogeneity and early detect the subclonal events within tumor. During the last years, progress in biotechnology, genomics, and molecular pathology determined improvements in understanding of tumor biology, leading to the discovery of several potential tumor biomarkers, suitable for clinical use. The identification of molecular biomarkers in clinical oncology and the advent of the immunotherapy have significantly modified the natural history of many tumors.In this chapter, we will summarize the key concepts related to biology and natural history of tumors, describing the model of cancer clonal evolution and discussing how the understanding of biological processes may affect the natural history of the disease.