In two phase carcinogenesis, carcinogen initiated cells may never develop into tumors unless tissue homeostasis is disturbed by tumor promoters, causing inflammation and/or proliferation. Mutatis mutandis, the same applies to viral carcinogenesis, even with highly transforming viruses. Moreover, disseminating cells from frank malignancies may remain dormant over many years, unless “awakened”. This brief survey will discuss mechanisms for awakening. They include:
i). Morphogenetic rearrangements of tissue architecture;
ii). Inflammation, induced by the impact of microorganisms, viruses, or by functional dysegulation;
iii). Changes in the stromal microenvironment.