Mechanisms of drug resistance in colon cancer and its therapeutic strategies

Table 1 Selective anticancer drug substrates and inhibitors of ATP-binding cassette transporters P-glycoprotein, multidrug resistance-associated protein 1 and breast cancer resistance protein

Transporters	Anticancer drug substrates	Inhibitors	Ref.
P-gp (ABCB1)	Actinomycin D, bisantrene, colchicine, daunorubicin, dasatinib, docetaxel, doxorubicin, epirubicin, etoposide, imatinib, irinotecan, mitoxantrone, nilotinib, paclitaxel, saquinavir, teniposide, topotecan, vinblastine, vincristine, vindesine, vinorelbine	Biricodar, chloroquine, cryptotanshinone, curcumin, cyclosporin A, dexverapamil, dihydrotanshinone, dofequidar, laniquidar, nifedipine, quinidine, sipholenol A, tamoxifen, tariquidar, valspodar, verapamil, zosuquidar	[12,66-68,132,133]
MRP1 (ABCC1)	Colchicine, doxorubicin, etoposide, imatinib, irinotecan, methotrexate, mitoxantrone, saquinavir, topotecan, vinblastine, vincristine	Biricodar, celecoxib, curcumin, dinaciclib, dofequidar, flavonoids, ibrutinib, myricetin, sulindac, tariquidar	[133-141]
BCRP (ABCG2)	Bisantrene, daunorubicin, doxorubicin, etoposide, gefitinib, imatinib, irinotecan, methotrexate, mitoxantrone, SN-38, teniposide, topotecan, vincristine	Biricodar, corticosterone, curcumin, cyclosporin A, elacridar, gefitinib, imatinib, ketoconazole, lopinavir, nifedipine, quercetin, rotenoids, stilbenoids, tariquidar, tectochrysin	[12,142-146]

BCRP: Breast cancer resistance protein; MRP1: Multidrug resistance-associated protein 1; P-gp: P-glycoprotein.

Table 2 Potential agents to overcome resistance of cancer cells to apoptosis (non-exhaustive list)

Restoration of apoptotic signals		Alternative cell death		Ref.
BH3 mimetics	EGFR inhibitors	Autophagy inducers	Agents with p53-independent toxicity
ABT-199 (venetoclax), ABT-263 (navitoclax), ABT-737, apogossypol, apogossypolone, gossypol, maritoclax, obatoclax, sabutoclax	Afatinib, cetuximab, dacomitinib, erlotinib, gefitinib, lapatinib, matuzumab, neratinib, nimotuzumab, panitumumab, zalutumumab	Clonidine, cryptotanshinone, curcumin, dihydrotanshinone, evodiamine, genistein, helenalin, monascuspiloin, oridonin, paclitaxel, quercetin, rapamycin, resveratrol, sodium valproate, verapamil	Betulinic acid, crocetin, cryptotanshinone, dihydrotanshinone, epigallocatechic-3-gallate, genistein, a-iso-cubebene, resveratrol, triptolide, thymoquinone, ursolic acid	[91,112-115,117,120,121,124,127-129,147-156]

EGFR: Epidermal growth factor receptor.