TABLE 2.
Common mutation types of crizotinib resistance and effective inhibitors.
| Type of ROS1 fusion | Mutation site | Mechanisms | Effective TKI |
|---|---|---|---|
| CD74-ROS1 | G2032R | Altered spatial structure of ROS1 domain interferes with drug binding and leads to resistance to ROS1 inhibitors | cabozantinib |
| repotrectinib | |||
| D2033N | Alteration in the electrostatic force on the outer surface of the ATP-binding site and a rearrangement of ATP-binding site | lorlatinib | |
| cabozantinib | |||
| repotrectinib | |||
| L2026M | Leucine to methionine substitution | ceritinib | |
| lorlatinib | |||
| cabozantinib | |||
| repotrectinib | |||
| SLC34A2-ROS1 | L2155S | Protein dysfunction | lorlatinib |
| cabozantinib | |||
| repotrectinib | |||
| EZR-ROS1 | S1986F/Y | Increased kinase activity | lorlatinib |
| cabozantinib | |||
| repotrectinib |