Systems-level biomarkers identification and drug repositioning in colorectal cancer

Table 3 Drug repurposing candidates for the prevention and/or treatment of colorectal cancer

Drug (s)	Pharmacological class	Original indication	CRC effect	Ref.
Based on computational approaches
GW-8510, ethacrynic acid, ginkgolide A and 6-azathymine	GW-8510: Inhibitor of cyclin-dependent kinase-2; ethacrynic acid: Diuretic; ginkgolide A: Platelet-activating factor antagonist; 6-azathymine: D-3-aminoisobutyrate-pyruvate aminotransferase inhibitor	GW-8510: Prevention of chemotherapy-induced alopecia; ethacrynic acid: Treatment of high blood pressure and swelling; ginkgolide A: Treatment of a wide variety of cognitive and vascular disorders	Inhibit CRC cells	Chung et al[97], 2014
		6-azathymine: Has antibacterial and antiviral activities
GW-8510	Inhibitor of cyclin-dependent kinase-2	Prevention of chemotherapy-induced alopecia	CRC therapeutic agent which targets RRM2 inhibition	Hsieh et al[98], 2016
Abemaciclib	Anti-neoplastic	Treatment of advanced or metastatic breast cancers	CRC therapeutic agent which targets FABP6	Liñares-Blanco et al[99], 2020
AG 957, Ro-28-1675, Brazilin, Importazole, PD 407824	AG 957: Inhibitor; Ro-28-1675: Activator; Brazilin: Anti-inflammatory agent; Importazole: Inhibitor; PD 407824: Indoles and derivatives	AG 957: Protein tyrosine kinase; Ro-28-1675: Glucokinase activator; Brazilin: NF-kappaB inhibitor and a hepatoprotective agent; Importazole: Transport receptor importin-β; PD 407824: Wee1/Chk1 inhibitor	CRC drug candidates	Beklen et al[100], 2020
Based on clinically or experimentally validated approaches
Metformin	Antidiabetic agent	Treatment of type 2 diabetes mellitus	Reduces pre-cancerous lesions and cancerous cell proliferation	Jia et al[102], 2015
			Results in better overall survival	Bishnoi et al[104], 2018
			Causes both apoptosis and autophagy of cultured HT29 cells	Sena et al[103], 2018
Aspirin	Nonsteroidal anti-inflammatory	Relieves minor aches, pains, and fevers	Regular, long-term aspirin use reduces CRC risk	Chan et al[105], 2005
			Reduces CRC cell proliferation	Reddy et al[106], 2006
			Daily use for about 5 yr is efficient in prevention, with a latency time of about 10 yr	Flossmann et al[107], 2007
			Restrains CRC tumor metastasis	Jin et al[108], 2019
Cimetidine	Gastrointestinal agent	Treatment of ulcers and gastroesophageal reflux disease	Short course of cimetidine treatment has an impact on patient survival	Kelly et al[110], 1999
			Inhibits the adhesion of CRC cells and represses spread of cancer cells	Kobayashi et al[111], 2000
			Reduces frequency of metastasis and increases survival rate	Matsumoto et al[112], 2002
			Prolongs the probability of recurrence	Ali et al[113], 2018
Diclofenac	Nonsteroidal anti-inflammatory	Relieves pain and inflammation	Contributes to tumor growth inhibition in colon cancer	Falkowski et al[116], 2003
			Promotes cell death	Arisan et al[117], 2018
Chloroquine	Antimalarial	Treatment of malaria	Increases cell inhibition and decreases reproduction	Sasaki et al[119], 2010
			Use at high doses (40–160 μM) encourages lysosomal membrane permeabilization and cell death	Park et al[120], 2014
Sulindac	Nonsteroidal anti-inflammatory	Reduces pain, swelling, and joint stiffness due to arthritis	Decreases final tumor counts and prevents CRC especially when given in intermittent doses	Chandra et al[122], 2017
			Decreases polyp count	Davis et al[123], 2020
Mesalazine	Anti-inflammatory	Treatment of mild to moderate ulcerative colitis	Decreases CRC cell number and enhances apoptosis	Reinacher-Schick et al[125], 2003
			Causes CRC cell cycle arrest and cell death	Koelink et al[126], 2010
Disulfiram	Enzyme inhibitor	Alcohol addictive disorder	Promotes cell viability inhibition	Stenvang et al[128], 2018
Erlotinib	Anti-neoplastic	Treatment of non-small cell lung and pancreatic cancer	Contributes to enhanced progression-free survival and overall survival of metastatic CRC patients	Shi et al[130], 2017

CRC: Colorectal cancer.