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Overriding Adaptive Resistance to Sorafenib Through Combination Therapy With Src Homology 2 Domain–Containing Phosphatase 2 Blockade in Hepatocellular Carcinoma

The survival benefit of sorafenib for patients with hepatocellular carcinoma (HCC) is unsatisfactory due to the development of adaptive resistance. Increasing evidence has demonstrated that drug resistance can be acquired by cancer cells by activating a number of signaling pathways through receptor tyrosine kinases (RTKs); nevertheless, the detailed mechanism for the activation of these alternative pathways is not fully understood.