Fig. 1: Hallmarks of cancer clonal heterogeneity and clonal attack strategy.

A The interactions between extracellular factors (microenvironment, immune response/inflammation, infection, microbiota, and treatment) and intracellular factors (epigenetics, signaling, metabolism, DNA damage response = DDR, transcription, splicing, cell cycle, and other) generate unique clonal composition in individual tumors. B Standard treatment removes and/or reduces some clones, while others survive eventually facilitating the emergence of new clone(s). Conversely, clonal attack targets all clones at the same time thus eradicating the disease.