Dominant mechanisms of primary resistance differ from dominant mechanisms of secondary resistance to targeted therapies

摘要: The effectiveness of targeted therapies is currently limited, as almost all patients eventually acquire resistance within year/year and a half from therapy initiation small subset fail to respond at all, demonstrating intrinsic resistance. aim this review was determine the potential common features differences between mechanisms acquired by analyzing established resistance-generating alterations for ten FDA-approved drugs. frequency underlying shows distinctive pattern, where dominant include aberrations signals downstream or upstream protein refer lesions in target itself target-level that can mimic compensate function. It appears during evolution resistance, tumor cell inclined preserve same oncogene addiction on it had prior drug administration. On other hand, develops early tumorogenesis based randomly selected mutated non-targeted signaling pathways, leading acquisition cancer hallmarks. In general, there an overlap but occurrence distribution are significantly different. Focus should be placed different group genes pursuing predictive markers therapies.