Implications of Therapy-Induced Genetic/Epigenetic Modulations of Tumor Progression and Tumor Cell Heterogeneity for the Treatment of Cancer
Clinical oncologists and basic cancer researchers alike have gradually come to recognize the tremendous obstacle that intra-tumor cell heterogeneity poses for the treatment of cancer (1,2). No matter how seemingly ingenious or exhaustive a new form of cancer therapy seems to be, and even if it produces an initial dramatic response, in almost all cases mutant cell populations emerge which possess a very high degree of resistance to the therapeutic agent(s) used for the treatment. Up until a few years ago, this was thought to occur by a process similar to the one involved in the emergence and overgrowth of antibiotic-resistant bacteria as a result of their exposure to an antibiotic. This was shown to be due to the presence of very low frequency (i.e., “cryptic”) mutants which had spontaneously undergone a genetic mutation (making the cells antibiotic-resistant) prior to exposure of the bacteria to the antibiotic; the presence of the drug then acts as a potent selection pressure to promote the overgrowth of the antibiotic-resistant mutants.
KeywordsGene Amplification Thymidine Kinase Antineoplastic Agent Tumor Cell Population Asparagine Synthetase
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