Bypass Mechanisms of Resistance to Receptor Tyrosine Kinase Inhibition in Lung Cancer

Sci. Signal.  24 Sep 2013:
Vol. 6, Issue 294, pp. re6
DOI: 10.1126/scisignal.2004652

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In various cancers, somatic alterations in the genes that encode a class of proteins called receptor tyrosine kinases (RTKs) lead to increased cell proliferation. In such cancers, RTK inhibitors are often more effective than standard chemotherapy, markedly shrinking tumors and diminishing associated symptoms in patients. However, resistance to these inhibitors nearly always develops, thereby limiting their ultimate efficacy and patient benefit. Many studies show that resistance develops because of either a new mutation in the targeted RTK or a stimulation of downstream pathways mediated by an alternate RTK. Cancers are often resensitized to the original therapy by concomitant inhibition of the alternate RTK. In this mini-review, which contains one figure, one table, and 44 references, we summarize the known mechanisms of RTK-mediated resistance in lung cancer and the clinical challenges of preventing or overcoming resistance.