Holland-Frei Cancer Medicine

An enigma for cancer medicine lies in its complexity and variability, at all levels of consideration. The hallmarks of cancer constitute an organizing principle that provides a conceptual basis for distilling the complexity of this disease in order to better understand it in its diverse presentations. This conceptualization involves eight biological capabilities—the hallmarks of cancer—acquired by cancer cells during the long process of tumor development and malignant progression. Two characteristic traits of cancer cells facilitate the acquisition of these functional capabilities. The eight distinct hallmarks consist of sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, deregulating cellular energetics and metabolism, and avoiding immune destruction. The principal facilitators of their acquisition are genome instability with consequent gene mutation and tumor-promoting inflammation. The integration of these hallmark capabilities involves heterotypic interactions among multiple cell types populating the “tumor microenvironment” (TME), which is composed of cancer cells and a tumor-associated stroma, including three prominent classes of recruited support cells—angiogenic vascular cells (AVC), various subtypes of fibroblasts, and infiltrating immune cells (IIC). In addition, the neoplastic cells populating individual tumors are themselves typically heterogeneous, in that cancer cells can assume a variety of distinctive phenotypic states and undergo genetic diversification during tumor progression. Accordingly, the hallmarks of cancer—this set of necessarily acquired capabilities and their facilitators—constitute a useful heuristic tool for elucidating mechanistic bases and commonalties underlying the pathogenesis of diverse forms of human cancer, with potential applications to cancer therapy.