In 2000, Hanahan and Weinberg named the hallmarks of cancer as self-sufficiency in growth signals; insensitivity to anti-growth signals; evading apoptosis, with limitless replicative potential; sustained angiogenesis; tissue invasion; and metastasis. (Hallmarks I). In 2011, Hanahan and Weinberg, added—reprogramming energy metabolism; evading the immune response; genome instability and mutation; and tumor-promoting inflammation. (Hallmarks II).

In 2017, Fouad and Aanei, revisited the hallmarks of cancer and identified hallmarks as selective growth and proliferation advantage; altered stress response favoring overall survival; vascularization; invasion and metastasis; metabolic rewiring; abetting a microenvironment; and immune modulation. (Hallmarks III). Fouad and Aanei said cancer acquires evolutionary-advantageous characteristics, which promote transformation of normal cells into malignant ones, through continuous insults, which results in alterations in epi-genes, chromosomal numbers, chromosomal arrangements, heterotypic interactions, and defective DNA repair; and promotes progression of malignant cells while sacrificing and/or exploiting host tissue. Weinberg opined we seem to have come full circle—from overwhelming complexity to simplicity, and back to overwhelming complexity. See https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5446472/.

We should now return to a simple understanding that Hallmarks I, II and III can be explained based on the known microbiology and effects of immortal intracellular pathogens. Chronic intracellular infection, which also infects immune cells, combined with co-infections and environmental triggers, over time, cause the transformation of infected cells into cancer.