Evolvability and emergence of tumor heterogeneity as a space–time function

•Endogenous retroviruses are a major cause of the intra- and inter-tumor heterogeneity.•Tumor cells de-differentiate to acquire cancer stem cell properties and metastasize.•Multiple factors that contribute to tumor heterogeneity exhibit space–time function.•Tumor heterogeneity throws up huge challenges to successful anti-cancer therapy.