Fig. 5. The common resistance mechanisms of TKIs in tumors.

Dysregulation of tyrosine kinase activity is frequently found in tumors, of which the most clinically relevant and most studied is the abnormal expression of BCR-ABL1. BCR-ABL1 mutation was first identified as a point mutation caused by the substitution of isoleucine for threonine at position 315, which occurs most frequently in drug-resistant patients, and the effectiveness of TKIs is highly dependent on the interaction between BCR-ABL1 and THR, and the failure of TKI binding to the target kinase caused by the overexpression of BCR-ABL1 and fusion gene mutation may lead to drug resistance.