Table 1.

Summary of mechanism of chemotherapeutic resistance in lung cancer.

Mode of Action	Target Entity	Chemotherapeutic Agent	References
DNA repair system	Upregulation of: ERCC1 DNA Polymerase	Platinum compounds	[94,95]
Drug efflux	Upregulation of ABC family transporters: ABCC1/MRP1 ABCC3/MRP3 ABCB1/MDR1 ABCC10/MRP7 ABCB1/MDR1/p-glycoprotein ABCC6/MRP6 ABCC11/MRP8	Platinum compounds Microtubule-targeted compounds Etoposide Gemcitabine Pemetrexed	[33,34,35,36,37,38]
Prosurvival signaling	Upregulation of: EGFR PI3K/Akt MAPK Calpain Sphk1	Platinum compounds Microtubule-targeted compounds Pemetrexed	[42,43,44]
Cell cycle arrest	Upregulation of: Bcl-2 Bcl-XL Autophagy	Platinum compounds Gemcitabine Microtubule-targeted compounds	[46,47,96]
Epigenetic regulation	Promoter methylation of IGFBP3 and FOXF1 Upregulation of KDM3B Deregulation of circadian rhythm	Platinum compounds	[67,97,98,99]
MicroRNA	Upregulation of: miR-106a, miR- 31, miR-15b, miR-27a, miR-223, miR-205, miR-92b, miR-224, miR-34c-5p, miR-181a, miR-135a, miR 197-3p, miR-222-3p downregulation of: miR-101-3p, miR-181, miR-589, miR-1244, miR-29c, miR-630, and miR-197 miR-16, miR-17-5p, miR-216b, miR-200b, miR-363-3p	Platinum compounds Microtubule-targeted compounds Etoposide Gemcitabine	[16,84,85,86,87]
EMT/CSC	Upregulation of: EMT phenotype Notch signaling Wnt signaling Shh signaling	Platinum compounds Microtubule-targeted compounds Etoposide Pemetrexed	[100,101]
Tumor microenvironment	Upregulation of: Hypoxia CAF PDL-1	Platinum compounds	[102,103,104]
Cancer metabolism	Upregulation of: PGC1α and glutamine metabolism Downregulation of: OXPHOS and glycolysis	Platinum compounds	[90,105]