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Second, as mentioned above, c-Met inhibitors which target the interaction between HGF and c-Met may lose efficacy owing to cell attachment (Wang et al., 2001), gene amplification of c-Met, DCP binding to c-Met (Suzuki et al., 2005), gene mutation in the c-Met activation loop (Okuma and Kondo, 2016) and crosstalk with other membrane receptors (Garcia-Vilas and Medina, 2018)