New Strategies in Reversing Resistance to Tyrosine Kinase Inhibitors Based on Competitive Release Phenomenon of Cancer Cell Evolution Dynamics
SONG Xiujun, LI Bin*
One of the major reasons for the carcinogenesis and progression of cancer was the mutation of oncogenes and overproduction or activation of according oncoproteins. TKI (tyrosine kinase inhibitor) targeting special oncoprotein can inhibit the growth of cancer cells, and thus is recommended as a frontline in cancer treatment by a series of guidelines. However, the phenomenon of resistance to TKI will eventually occurred in cancer cells. Therefore, reversing or delaying TKI resistance has become the hot topic for cancer therapeutics. The mechanisms of TKI resistance include secondary mutations within oncogenes, amplification or signaling pathway activation of other genes, or the transformation of pathology type. Recently, with the advance of evolution theory in cancer progression, the concept of “competitive release” leading to dominance clone of drug-resistant cells has been proposed. We herein sum the related references about TKI resistance due to the “competitive release” of defiance subclones during the TKI therapy, and also we elaborate recent data about how to delay or reverse TKI resistance emerging from this circumstance of “competitive release”.
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