What to read after Cancer Genome and Tumor Microenvironment?

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.