Molecular targets of ivermectin as a potential repurposed drug in cancer therapy: A scoping review

Table 2 Mechanisms, molecular targets, and drug-drug interactions of ivermectin across different cancer types

Cancer type	Mechanism of action	Molecular targets	Co-administered drugs	DDI mechanism	Efficacy of combination therapy
Breast cancer	G0/G1 arrest; apoptosis; stem cell inhibition; MDR reversal	Cyclin D/E, PCNA, p21, PAK1/Akt/mTOR, ALDH, ROS	Tamoxifen, docetaxel, cyclophosphamide	MDR inhibition; complementary antiproliferative synergy	Reduced tumor size and weight; enhanced apoptosis; no toxicity
Prostate cancer	Synthetic lethality via FOXA1/Ku70/Ku80; AR/E2F1 suppression; DNA damage	FOXA1, Ku70/Ku80, AR, BRCA1, Rad51	Enzalutamide	Enhanced apoptosis; reduced IC50 of ivermectin	Tumor suppression in vitro and in vivo; increased
Ovarian cancer	Chemoresistance reversal via P-gp inhibition; apoptosis enhancement	P-gp, HMGCR, mutant p53, PAK1/Akt/mTOR, YAP1	Paclitaxel, pitavastatin	Increased intracellular drug retention; synergistic apoptosis	Synergy in resistant lines: Reduced viability, increased caspase activity
Bladder cancer	ATM/p53-mediated apoptosis; ROS generation; mitochondrial dysfunction	ATM/CHK2/p53/p21, Bax/Bcl-2, caspase-3, PARP	None reported	Not applicable	Reduced tumor volume; low toxicity; increased apoptosis markers
HCC	Stemness suppression; EMT inhibition; apoptosis induction	mTOR/STAT3, EMT, Nanog, Sox2, Oct4	Sorafenib	Suppression of mTOR/STAT3 and EMT pathways	Synergistic tumor suppression; reduced migration and stemness markers
Colorectal cancer	ROS-mediated mitochondrial apoptosis; S-phase arrest; migration inhibition	Wnt/β-catenin, Bax/Bcl-2, PARP, caspase-3/7, integrin β1/FAK	Adriamycin, vincristine	EGFR-independent inhibition of metastasis	Synergy in drug-resistant models; reduced viability and migration
Cholangiocarcinoma	Apoptosis, autophagy, pyroptosis; MDR reversal; stem cell modulation	PAK1, Akt/mTOR, EGFR, STAT3, YAP1, Wnt/β-catenin, P2X4/P2X7/NLRP3	Cisplatin, paclitaxel, erlotinib	MDR inhibition; EGFR/HER2 modulation	Enhanced tumor cell death; restored drug sensitivity
Gastric cancer	Apoptosis and autophagy; stem cell suppression; proliferation inhibition	PAK1, Akt/mTOR, Wnt/β-catenin, YAP1	Not reported	Not specified	Inhibition of proliferation and angiogenesis; stem cell suppression
Lung cancer	Apoptosis via ROS and mitochondrial dysfunction; EGFR modulation	EGFR, STAT3, YAP1, ROS pathways	Erlotinib, cetuximab	EGFR/HER2 modulation; MDR reversal	Enhanced apoptosis and drug sensitivity

DDI: Drug-drug interaction; MDR: Multidrug resistance; PCNA: Proliferating cell nuclear antigen; PAK1: P21-activated kinase 1; FAK: Focal adhesion kinase; ATM: Ataxia telangiectasia mutated; FOXA1: Forkhead box A1; YAP1: Yes associated protein 1; HCC: Hepatocellular carcinoma; IC₅₀: Half maximal inhibitory concentration; Akt: Protein kinase B; mTOR: Mammalian target of rapamycin; ALDH: Aldehyde dehydrogenase; ROS: Reactive oxygen species; Ku70: Lupus Ku autoantigen protein p70; Ku80: Lupus Ku autoantigen protein p80; AR: Androgen receptor; BRCA1: Breast cancer gene 1; Rad51: RAD51 recombinase; P-gp: P-glycoprotein; HMGCR: 3-hydroxy-3-methylglutaryl-CoA reductase; CHK2: Checkpoint kinase 2; Bax: Bcl-2-associated X protein; Bcl-2: B-cell lymphoma 2; PARP: Poly (ADP-ribose) polymerase; STAT3: Signal transducer and activator of transcription 3; EMT: Epithelial-mesenchymal transition; Nanog: Nanog homeobox; Sox2: SRY-box transcription factor 2; Oct4: Octamer-binding transcription factor 4; EGFR: Epidermal growth factor receptor; P2X4: P2X purinoceptor 4; P2X7: P2X purinoceptor 7; NLRP3: NLR family pyrin domain containing 3; HER2: Human epidermal growth factor receptor 2.