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

Table 4 Summary of in vivo efficacy outcomes of ivermectin-drug interaction

Animal model	Tumor type	Drug(s) co-administered with ivermectin	Primary outcomes
Nude mice, Mob1b+/- mice	Liver cancer	Tamoxifen, paclitaxel, cisplatin, erlotinib, cetuximab, dasatinib, daunorubicin, cytarabine, docetaxel	Improved tumor suppression
Balb/c mice (murine JC breast cancer model)	Breast cancer (triple negative, and ER positive), ovarian cancer, prostate cancer	Docetaxel, cyclophosphamide, tamoxifen	Synergy with all 3 drugs with decreased tumor size
Xenograft mouse model (BALB/c-nude mice) using 22RV1 cells in castrated mice	Prostate cancer: Models used include hormonesensitive (LNCaP), castrationresistant prostate cancer (C42), and ARvariant positive CRPC (22RV1)	Enzalutamide	Enhanced antiproliferative effect
			Decreased Ki67 and PSA staining
			Increased γH2A.X in tumor tissue
3D cell culture model	High-grade serous carcinoma (ovarian cancer; chemoresistant)	Paclitaxel	No in vivo survival or tumor data
SNU-182 xenograft in SCID mice	Advanced hepatocellular carcinoma	Sorafenib	Suppressed and reversed tumor growth without toxicity compared to monotherapy
Xenograft models in BALB/c nude mice	Multiple cancers, mainly focusing on multidrug-resistant colorectal cancer (HCT8/VCR)	Adriamycin, vincristine	Inhibited cell migration
6-week-old male BALB/c nude mice xenografts (KYSE30 cells)	Esophageal squamous cell carcinoma	Chloroquine, tocopherol	Chloroquine reduced ivermectin cytotoxicity
			Tocopherol restored cell viability, reducing ivermectin efficacy
Mouse xenograft models of human MM cell line ARD (female 7-week-old severe immunodeficient NOD-Prkdcscid IL2rgtm1/Bcgen mice); toxicity: Balb/c mice	Multiple myeloma	Bortezomib (proteasome inhibitor)	Synergistic cytotoxicity with enhanced tumor growth inhibition
Xenografts in nude mice using KYSE150 cells	ESCC, including models of metastasis (lung metastasis)	Cisplatin and 5-fluorouracil	Increased sensitivity of cancer cells to cisplatin and 5-fluorouracil
			Decreased Ki67 staining in tumor tissue
In vivo xenograft leukemia (K562) model	CML (BCR-ABL positive)	Dasatinib, nilotinib	Improved tumor inhibition with drug combination

CRPC: Castration-resistant prostate cancer; ER: Estrogen receptor; ESCC: Esophageal squamous cell carcinoma; Ki-67: Antigen Kiel 67; MOB1B: MOB kinase activator 1B; MM: Multiple myeloma; LNCaP: Lymph node carcinoma of the prostate; PSA: Prostate-specific antigen; SCID: Severe combined immunodeficiency; CML: Chronic myeloid leukemia; JC: Junctional complex; AR: Androgen receptor; HCT8: Ileocecal adenocarcinoma cell line; VCR: Vincristine; ARD: Acid-related disorders; NOD: Non-obese diabetic; BCR: Breakpoint cluster region; ABL: Abelson murine leukemia viral oncogene homolog.