Metastasis and therapy resistance are the two major reasons that cancer continues to inflict considerable global mortality. This presentation will attempt to summarize the evidence that resistance to various modern treatments for cancer has ancient roots, and may in fact be just a part of a bigger story, that cancer itself represents a type of re-primitivization whereby an archaic, foundational program common to all eukaryotic organisms becomes de-repressed. This theory, known as ‘atavism’ seeks to explain cancer as an organism rather than merely as a disease, and posits the relative uniformity and peculiar nature of the malignant phenotype as derived from, and adapted to, the Proterozoic Eon and its unique geochemistry. Eukaryotes not only arose in, but also had to have survived the exigencies of the Proterozoic. These include extra-terrestrial radiation unmitigated by any ozone layer; mega-eruptive volcanism with its multiple killing mechanisms of de-gassing, oceanic acidosis, metal poisoning, climate extremes, anoxia and food chain collapse; chemical poisoning from competitors; bolide impact; changing oxygen levels, and predation. Some of these phenomena are known to have coincided with, and probably caused, multiple mass-extinctions; yet some organisms were able to survive. These adaptive strategies, I have hypothesized, became entrenched in the ancient eukaryotic genome by selection, and as a consequence of de-repression atavism, are available again to cancer cells (but less so to normal cells) as resistance mechanisms to modern therapies. These modern treatments (various chemotherapies, radiotherapy, surgery and now immunooncologics), coincidentally or not, resemble these ancient existential threats, and can therefore be overcome by this prior ‘training’ selectively available to cancer cells.