Table 3.

Different mechanisms of resistance to ALK inhibitors and the role of radiation therapy. ALK: anaplastic lymphoma kinase, TKI: tyrosine kinase inhibitor.

Mechanisms of Resistance to ALK Inhibitors	Role of RADIOTHERAPY
ALK resistance mutations	In the case of slow progression under TKI
Other bypass signaling pathways (TP53, HER2/3 activation, protein kinase C activation, cKIT amplification, insulin-like growth factor 1-receptor activation, upregulation of SRC proto-oncogene expression, EMT, MAPK pathway reactivation, SRC activation, PIK3CA mutation, MET amplification)	In the case of slow progression under TKI
Role of hypoxia	Decreases resistance to TKIs
Inhibition of c-MYC	Improves sensitivity to TKIs
Role of immunomodulatory effects	Sensitizes to immunotherapy