Oncogenes and tumor suppressor genes had been traditionally
studied in the context of cell proliferation, differentiation,
senescence, and survival, four relatively cell-autonomous
processes. Consequently, in the late 80s-early 90s, neoplastic
growth was described largely as an imbalance between net cell
accumulation and loss, brought about through mutations in cancer
genes. In the last ten years, a more holistic understanding of
cancer has slowly emerged, stressing the importance of interactions
between neoplastic and various stromal components: extracellular
matrix, basement membranes, fibroblasts, endothelial cells of blood
and lymphatic vessels, tumor-infiltrating lymphocytes, etc. The
commonly held view is that changes in tumor microenvironment are
soft-wired, i.e., epigenetic in nature and often reversible. Yet,
there exists a large body of evidence suggesting that well-known
mutations in cancer genes profoundly affect tumor milieu. In fact,
these non-cell-autonomous changes might be one of the primary
reasons such mutations are preserved in late-stage tumors."
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