Table 1.

Tyrosine kinase inhibitors, their targets, and application in specific malignancies.

Generation of TKIs 1	Name	Chemical Structure	First FDA 2 Approval	Target	Disease	Children	Adults
I	Imatinib		2001	BCR-ABL1 3	CML 4	[33,34]	[35,36]
					Ph+ ALL 5	[37]	[38]
					GIST 6	[39]	[40,41]
					Brainstem gliomas, intracranial gliomas	[42]	[43]
	Crizotinib		2011	ALK 7, ROS1 8, c-MET 9	ALK-positive lung cancer	No data	[44]
					Intrinsic pontine glioma	[45]	No data
					Solid tumours (hepatocellular carcinoma, adrenal cortical carcinoma, Wilms’ tumour, neuroblastoma ganglioneuroblastoma, rhabdomyosarcoma, synovial sarcoma, epithelial myoepithelial carcinoma, Ewing sarcoma), anaplastic large-cell lymphoma	[46]	[47]
					Non-small-cell lung carcinoma	No data	[48]
	Sunitinib		2006	VEGFR 10, VEGFR2 11, VEGFR3 12, c- KIT 13, FLT3 14, CSF-1R 15, RET 16	Renal cell carcinoma	[49]	[50]
					GIST	[51]	No data
II	Regorafenib		2012	VEGF, EGFR 17	Liposarcoma	Clinical trial number NCT02085148	[52]
					GIST		[53]
					Hepatocellular carcinoma		[54]
	Dasatinib		2006	BCR-ABL1, Src 18, c-Kit, ephrin receptors	CML	[55,56]	[57]
					Ph+ ALL	[58]	[57]
	Bosutinib		2012	BCR-ABL1, Src	CML	Clinical trial number NCT04258943	[41,59]
					Glioblastoma	No data	[60]
	Nilotinib		2007	BCR-ABL1	Ph+ ALL	No data	[58]
					CML	[61]	[62]
					GIST	No data	[63]
					Glioma	[64]	No data
III	Ponatinib		2012	BCR-ABL1	Glioblastoma	No data	[65]
					ALL 19	Clinical trial number NCT04501614	[66]
					AML 20	No data	[67]
					CML	[68]	[69]
	Osimertinib		2020	EGFR	Non-small-cell lung carcinoma	No data	[70]
	Olmutinib		No FDA approval, approval in South Korea			No data	[71]
	Nazartinib		No approval, clinical trial number: NCT03040973		Non-small-cell lung carcinoma, advanced solid tumours	No data	[72]

¹ TKI, tyrosine kinase inhibitor; ² FDA, Food and Drug Administration; ³ BCR-ABL1, breakpoint cluster region and V-abl Abelson murine leukaemia viral oncogene homolog 1; ⁴ CML, chronic myeloid leukaemia; ⁵ Ph+ ALL, Philadelphia-chromosome-positive acute lymphoblastic leukaemia; ⁶ GIST, gastrointestinal stromal tumour; ⁷ ALK, anaplastic lymphoma kinase; ⁸ ROS1, ROS Proto-Oncogene 1, tyrosine kinase receptor; ⁹ c-MET, hepatocyte growth factor receptor; ¹⁰ VEGFR, vascular endothelial growth factor, ¹¹ VEGFR2, vascular endothelial growth factor 2; ¹² VEGFR3, vascular endothelial growth factor 3; ¹³ c-KIT, tyrosine protein kinase KIT; ¹⁴ FLT3, cluster of differentiation antigen 135; ¹⁵ CSF-1R, colony stimulating factor 1 receptor; ¹⁶ RET, proto-oncogene, rearranged during transfection; ¹⁷ EGFR, epidermal growth factor receptor; ¹⁸ Src, proto-oncogene, non-receptor tyrosine kinase; ¹⁹ ALL, acute lymphoblastic leukaemia; ²⁰ AML, acute myeloid leukaemia.