Table 1.

Key molecular function and mechanism of gene expression of resistance genes.

Resistant genes	Sites of expression	Functions	Role	Mechanism	Reference(s)
ABCB1/MDR1	Expressed broadly in the adrenal (RPKM=76.0), small intestine (RPKM=43.0) and 8 other tissues	Encodes permeability glycoprotein (P-gp) Involved in the efflux of drugs such as colchicine, taxol, vincristine, daunorubicin, irinotecan etc. It aids in the elimination of xenobiotics and other drug	It functions as a mediator in the development of anticancer drug resistance	Human ABCB1/MDR1 was isolated from the adrenal and it was found that cDNA, isolated from KB-C2.5, was associated with a Gly-to-Val substitution at position 185, in the predicted cytoplasmic loop between TM2 and TM3.This mutation increased colchicine resistance and decreased vinblastine resistance.	(94, 95)
ABCC1	Pervasive expression in testis (RPKM: Reads Per Kilobase of a transcript, per Million mapped reads = 13.5), esophagus (RPKM = 9.9), and 25 other tissues	Encodes multi-drug resistance-associated protein 1 (MRP1). Transportation of drugs means responsible for drug efflux Encodes membrane glycoprotein with 190 kDa and 1531 amino acids	Chemotherapeutic resistance	The promoter region of the ABCC1 gene carries the AP-1 site, which makes a complex with c-jun/junD. Correlation between the expression of ABC transporters and MAPK may lead to a cancer chemo-resistance pathway	(96, 97)
ABCC2	Expressed in the liver (RPKM=24.9), small intestine (RPKM=18.6), and three other tissues	Transport lipophilic substrates with sulfate, glutathione, glucuronate It can regulate the pharmacokinetics of many drugs. ABCC2 has a function in endogenous metabolites like biliary secretion. Transport variety of xenobiotics	Chemotherapeutic resistance	In TE14 and TE5 cell lines, ABCC2 appearance was higher and showed powerful resistance to CDDP. ESCC cell lines that contain more ABCC2 show more resistance to CDDP than lower containment of ABCC2. To confirm the role of ABCC2 in drug resistance, the ABCC2 gene was silenced with siRNAs into the TE14 cell line raised reactivity to CDDP	(98–100)
ABCC5	Expressed in the stomach (RPKM=10.1), spleen (RPKM=6.9, and 24 other tissues	Capable of shifting nucleotide analogs Preparedness for carrying methotrexate Transport exogenous glutamate analogs	Resistance to thiopurine anticancer drugs	Paclitaxel is a chemotherapeutic drug against neck and head cancer. Fork headbox (FOX) molecules are responsible for paclitaxel drug resistance. A molecular study reveals that ABCC5 with FOXM1 was highly expressed in nasopharyngeal carcinoma cells that were paclitaxel-resistant. ABCC5 gene transcription is controlled by binding of FOXM1 at the FHK consent pattern of the promoter	(101, 102)
ABCG2	Expressed broadly in the kidney (RPKM=44.7), placenta (RPKM=44.0) and 23 other tissues	ABCG2 encodes breast cancer resistance protein (BCRP) It fuctions as a xenobiotic transporters to exclude xenobiotics from brain Involved in brain-to-blood efflux It plays a vital role in the multidrug resistance phenotype of several cancer cell lines	Involved in resistance to mitoxantrone, daunorubicin and doxorubicin	Increased ABCG2 expression has been linked to cancer stem cells. The proximal miRNA response element (MRE) of ABCG2 is located in the 3’-UTR of ABCG2 mRNA in various cancer cell lines. Interestingly, it was found that this putative MRE of ABCG2 was lost in drug resistant cells and, therefore, the drug resistant cancer cells can evade ABCG2 mRNA degradation and protein synthesis repression mediated by miRNAs, leading to over-expression of ABCG2	(103–105)
Bcl-2	Expressed broadly in the thyroid (RPKM=21.9), spleen (RPKM=9.1), and 20 other tissues	By halting cell death, Bcl-2 multiplications total cell number. They could modify the shape and energetics of mitochondria At the time of viral infections, Bcl-2 may modify innate immunity	Involved in resistance to chemotherapeutics and glucocorticoids	Bcl-2 is an integral part of the mitochondrial and ER membranes. Bcl-2 is the cardinal pro-survival member that belongs to Bcl-2 ancestry. Bcl-2 is capable of binding to the inositol triphosphate receptors, and besides, Bcl-2 confiscates BH3. Membrane glycoprotein complexes work instead of membrane calcium channels that impaired calcium-mediated apoptosis. Overexposed Bcl-2 is also responsible for chemotherapy resistance	(106, 107)
EGFR	Expressed broadly in the placenta (RPKM=36.6), skin (RPKM=15.6), and 22 other tissues	EGFR increases the cell endurance pathway by both kinase-dependent and kinase-independent mechanisms Ligand-operated EGFR triggers the proliferation of cells. Ligand Mediated EGFR hinders autophagy	Involved in propagating cells	Binding with argonaute two and phosphorylate this protein via EGFR results in tumor suppressor miRNAs’ retardation, promoting cancer cell durability. EGFR hinders autophagy directly through the phosphorylation of a critical subunit of autophagy initiation complex Beclin-1	(108, 109)
TP53	Expressed in the spleen (RPKM=13.2), lymph node (RPKM=13.1), and 25 other tissues	Encodes p53 protein Regulates cell growth Restore DNA damage Control metabolism of cancer Control cell death	Increase resistance to cisplatin, doxorubicin, gemcitabine, tamoxifen and cetuximab	Cancer-deduced p53 mutants are known as TP53 mutate gene. Approximately among 74% of missense mutations, 80% of them occur in the DNA-binding domain (DBD) of the p53 Two types of p53 mutants are known: DNA-contact mutants and conformational mutants Most of the p53 mutants lose track of native-type function, and some p53 mutants have been obtained GOF (gain-of-functions) that move up chemo-resistance	(110, 111)