Chapter 56: Cancer: Biochemical Foundations

Cancer: Biochemical Foundations explores the etiology of carcinogenesis, identifying environmental mutagens such as radiation and chemical carcinogens—detectable via the Ames assay—as well as oncogenic viruses and hereditary factors as primary causes of the DNA damage that initiates tumor formation,. A central distinction is drawn between proto-oncogenes, which drive cell growth and become oncogenic through dominant gain-of-function mechanisms like chromosomal translocation, promoter insertion, gene amplification, or point mutations (exemplified by RAS and MYC), and tumor suppressor genes such as RB and P53, which function recessively and typically require the inactivation of both alleles to lose their growth-inhibitory or genomic caretaking functions,. The text details the multistep nature of tumor progression, illustrated by the sequential genetic alterations in colorectal cancer involving APC, K-RAS, and downstream signaling pathways,. Key biological hallmarks of cancer are analyzed, including the evasion of apoptosis through dysregulated caspase cascades and imbalances in pro-apoptotic (BAX) and anti-apoptotic (BCL-2) proteins, the reactivation of telomerase to ensure replicative immortality, and the stimulation of angiogenesis via hypoxia-inducible factors (HIF-1) and VEGF to secure blood supply,. The chapter further elucidates metabolic reprogramming known as the Warburg effect, where tumor cells prioritize aerobic glycolysis and specific pyruvate kinase isozymes (PKM2) to support biomass synthesis rather than pure energy production,. Additional topics include the critical role of the tumor microenvironment and inflammation, the influence of epigenetic modifications and microRNAs, and the mechanisms of metastasis facilitated by epithelial-to-mesenchymal transition (EMT) and matrix metalloproteinases (MMPs),. Finally, the summary covers clinical applications, from the use of tumor biomarkers like PSA and CEA for monitoring to the development of precision therapies such as tyrosine kinase inhibitors (imatinib) and immunotherapy, highlighting the shift toward personalized medicine based on genomic profiling,.