Table 1.

Drug repurposing cases for treating malignant systems

Sr No.	Original indication	Name of the Drug	Repurposing immunotherapy used for treating type of cancer	Mode of action	Reference
1	Bone remodeling	Denosumab	Melanoma	M1 macrophage activation	[23,157]
				T-cell activation
				Production of nuclear factor kappa B
				Dendritic cell survival and function
2	Antibiotic	Doxycycline	Breast cancer	Suppression of stem cell marker	[158,159]
				Inhibition of Autophagy
		Tigecycline	Ovarian cancer/Myeloid leukemia	Inhibition of mitochondrial translation	[160]
				Suppression of MYC, HIFs, PI3K/AKT or AMPK-mediated mTOR, cytoplasmic p21 CIP1/Waf1, and Wnt/β-catenin signaling
3	Viral Infection	Ritonavir	Ovarian cancer/Melanoma	AKT signaling Suppression	[161]
				Apoptosis
4	Antiretroviral Drug-HIV-1 integrase (IN) inhibitor	L-870810	Cancer	Cytotoxicity	[162,163]
				Blocking oncogenic kinases
5	Anti-neurodegenerative agent	Benserazide	Colon cancer	Suppression of M2 splice isoform of pyruvate kinase (PKM2)	[164,165]
			Melanoma
		Riluzole	Pancreatic Cancer	Suppressing the Wnt-β-catenin pathway	[166]
6	Anti-bacterial agent	Ciprofloxacin	Colon cancer	Reversal of MDR	[17,167]
7	Fungal infection	Enilconazole	Colorectal cancer	Suppression of PI3K/AKT pathways	[168]
8	Malaria	Chloroquine	Glioblastoma	Autophagy inhibition	[169]
				Reduction of tumor hypoxia
9	Antipsychotic drugs	Chlorpromazine	Glioblastoma	Inhibition of cytochrome c oxidase	[170]
		Risperidone	Colorectal Cancer	Apoptosis	[171]
				Anti-proliferative activity
10	Antidepressants	All-trans retinoic acid (ATRA)	Acute myeloid leukemia	Suppression of PKCβ, MEK/ERK and Akt activity	[172]
11	Cardiovascular Prevention/antihypertensive drug	Losartan	Ovarian cancer	Apoptosis	[173]
				Decrease in fibroblast infiltration
				Lower expression of collagen (Col)-I (Col)-III
				Lower expression of alpha smooth muscle actin (Acta2)
		Enalapril	Colorectal cancer	Activation of nuclear factor-κB (NF-κB) signaling proteins	[174]
				Upregulation of vascular endothelial growth factor (VEGF) expression
				Anti-proliferative activity
				Apoptosis
		Valsartan	Gastric cancer	Regulation of PI3K/AKT Pathways	[175,176]
		Telmisartan	Lung cancer/Gastric cancer	Induction of apoptosis	[177]
				Inhibition of cadherin-mediated activation FGFR signaling
				Inhibition of the PI3K/AKT pathway
		Irbesartan	Prostate cancer	Renin-angiotensin blockade	[176]
		Benazepril	Esophageal carcinoma	Inhibition of Ki-67 nuclear protein	[178]
				Inhibition of angiogenesis
		Digoxin	Prostate cancer	Inhibition of VEGF	[179]
				Inhibition of angiogenesis
		Fluvastatin	Breast cancer	Expression of Sirtuin 6 (SIRT6)	[180,181]
			Renal cancer	Activation of mTOR pathway
			endometrial cancer (EC)	Endoplasmic reticulum (ER) stress leading to aggresome formation
			Lung adenocarcinoma	Anti-proliferative activity
				Apoptosis
		Propranolol	Malignant Melanoma	Suppression of ERK/Cyclin D1/Rb/Cyclin E pathway	[182]
				Stimulation of G0/G1/S phase arrest
	Anti-inflammatory drugs	Ibuprofen	Gastric cancer	Apoptosis	[183,184]
				Inhibition of cell proliferation
				Inhibition of cyclooxygenase

Abbreviations: MYC, MYC Proto-Oncogene; HIF, Hypoxia-inducible factor; PI3K, phosphoinositide 3-kinases; AMPK, AMP-activated protein kinase; mTOR, Mammalian target of rapamycin; p21 CIP1/Waf1, cyclin-dependent kinase inhibitor p21; Wnt, Wingless-Type; Akt, Ak strain transforming; PK, pyruvate kinase; MDR, Multidrug resistance; PKCβ, Protein kinase C-β; ERK, Extracellular signal-regulated kinase; MEK, Mitogen-activated protein kinase kinase MEK; Col, collagen; Acta, alpha smooth muscle actin; NF-κB, nuclear factor-κB; VEGF, vascular endothelial growth factor; FGFR, fibroblast growth factor receptor; SIRT6, Sirtuin 6; ER, Endoplasmic reticulum.