In this section, we will discuss elements of cellular biology and immunology that have given insight into personalized genomically based treatment and fueled a revolution in cancer management.
Cancer represents a group of heterogeneous diseases ranging from slow to fast growing, low to high metastatic potential, and little to virulent lethality. Cancers are perverse “pseudo-organs” that, for the most part, are not a static collection of homogeneous cells, but rather a dynamic process (i.e., carcinogenesis).
Starting with the groundbreaking work of Garth Nicholson on the model of cell membranes—the Fluid Mosaic stability in repetitive short DNA sequences (microsatellites, aka MSI, or short tandem repeats), and genetic and immunologic heterogeneity. Examples of MSI are TATATATATATA (dinucleotide) or GTC GTC GTC GTC GTC GTC (trinucleotide microsatellite). These motifs act as “fillers” and do not have coding function, but they are important in terms of “genetic fingerprinting,” forensic medicine, and paternity testing; involve the risk of developing cancer; and are thought to affect the likelihood of response to immunotherapy and checkpoint inhibitors (Krontiris et al., 1993; Singer and Nicolson, 1972).