Angiogenesis, Inflammation & Therapeutics | Online ISSN  2207-872X
REVIEWS   (Open Access)

Repurposing Drugs for Overcoming Therapy Resistance in Colon Cancer – A Review

Mahdi Darvishi 1, Amir Mohammad Chekeni 2, Mohammad Fazelhosseini 1, Zeenat Iqbal 3*, Mohd Aamir Mirza 3*, Mohammed Aslam 4, Esra Tariq Anwer Bayrakdar 4

+ Author Affiliations

Journal of Angiotherapy 8(2) 1-23 https://doi.org/10.25163/angiotherapy.829423

Submitted: 12 November 2023  Revised: 22 January 2024  Published: 08 February 2024 

Oncology research seeks new therapies for aggressive CRC, utilizing repurposed drugs for accelerated and safer treatment approaches.

Abstract


Colorectal cancer is a common type of cancer worldwide. Colorectal cancer is a prevalent form of cancer that is observed globally. The survival prospects for individuals with advanced stages of this disease are notably diminished. The chance of getting colorectal cancer is 4% to 5%. Getting older, having chronic illnesses, and certain lifestyle choices raise the risk of getting colorectal cancer. Surgery, as well as neoadjuvant radiation treatment (for those affected by rectal cancer) and adjunctive chemotherapy (for stage III/IV colon cancer patients and high-risk stage II colon cancer patients), stand as the most employed therapeutic interventions. Treating CRC has improved, but the medicines are expensive and have side effects. Therefore, alternative methods that are more affordable and still effective need to be explored. The use of existing drugs to treat diseases is becoming more popular due to high attrition rates, economic burden, slow drug discovery, and development. Many methods have been proposed to find repurposed therapeutic candidates, which can save time and money. Repurposing drugs is more successful and efficient than creating new drugs for rare diseases. Using existing drugs for cancer treatment is a major priority. Non-cancer drugs should not be overlooked since they have the potential to address both identified and unidentified weaknesses in cancer. Unlike targeted therapy, old generic drugs used in multiple ways can benefit patients. This review delves into the present body of evidence regarding the utilization of established medications as a plausible therapeutic avenue for patients suffering from CRC. The focus is to illustrate the possible competitors and their complex ways of functioning, including medications that have the ability to combat malaria, parasitic infections, inflammation, high blood pressure, high cholesterol levels, and diabetes.

Keywords: Colon Cancer, Colorectal cancer (CRC), Drug Repurposing, Therapy Resistance, Anti-Helminthic Drugs, Nonsteroidal Anti-Inflammatory Drugs, Anti-Hypertensives, Antiarrhythmic Drugs,

References


Ahmad, A., Gupta, A., Ansari, M. M., Vyawahare, A., Jayamurugan, G., & Khan, R. (2019). Hyperbranched polymer-functionalized magnetic nanoparticle-mediated hyperthermia and niclosamide bimodal therapy of colorectal cancer cells. ACS Biomaterials Science & Engineering, 6(2), 1102-1111.

Ahmad, J., Garg, A., Mustafa, G., Ahmad, M. Z., Aslam, M., & Mishra, A. (2023). Hybrid Quantum Dot as Promising Tools for Theranostic Application in Cancer. Electronics, 12(4), 972.

Ahmad, M. Z., Ahmad, J., Aslam, M., Khan, M. A., Alasmary, M. Y., & Abdel-Wahab, B. A. (2021). Repurposed drug against COVID-19: nanomedicine as an approach for finding new hope in old medicines. Nano Express, 2(2), 022007.

Akagi, J., & Baba, H. (2019). Hydrogen gas restores exhausted CD8+ T cells in patients with advanced colorectal cancer to improve prognosis. Oncology reports, 41(1), 301-311.

Alaaeldin, R., Nazmy, M. H., Abdel-Aziz, M., Abuo-Rahma, G. E. D. A., & Fathy, M. (2020). Cell Cycle Arrest and Apoptotic Effect of 7-(4-(N-substituted carbamoylmethyl) piperazin-1-yl) Ciprofloxacin-derivative on HCT 116 and A549 Cancer Cells. Anticancer research, 40(5), 2739-2749.

Alburquerque-González, B., Bernabé-García, Á., Bernabé-García, M., Ruiz-Sanz, J., López-Calderón, F. F., Gonnelli, L., ... & Conesa-Zamora, P. (2021). The FDA-approved antiviral raltegravir inhibits fascin1-dependent invasion of colorectal tumor cells in vitro and in vivo. Cancers, 13(4), 861.

Ali, R., Toh, H. C., Chia, W. K., & ASCOLT Trial Investigators. (2011). The utility of Aspirin in Dukes C and High Risk Dukes B Colorectal cancer-The ASCOLT study: Study Protocol for a randomized controlled trial. Trials, 12, 1-8.

Al-Kuraishy, H. M., Al-Gareeb, A. I., Alzahrani, K. J., Alexiou, A., & Batiha, G. E. S. (2021). Niclosamide for Covid-19: bridging the gap. Molecular Biology Reports, 1-8.

Al-Majed, A. A., Bakheit, A. H. H., Abdel Aziz, H. A., Alajmi, F. M., & AlRabiah, H. (2017). Propranolol. Profiles Drug Subst Excip Relat Methodol 42: 287–338.

Anirudh, B. V. M., & Ezhilarasan, D. (2021). Reactive Oxygen Species–Mediated Mitochondrial Dysfunction Triggers Sodium Valproate–Induced Cytotoxicity in Human Colorectal Adenocarcinoma Cells. Journal of Gastrointestinal Cancer, 52, 899-906.

Antonello, R. M., Di Bella, S., Betts, J., La Ragione, R., Bressan, R., Principe, L., ... & Lagatolla, C. (2021). Zidovudine in synergistic combination with fosfomycin: an in vitro and in vivo evaluation against multidrug-resistant Enterobacterales. International journal of antimicrobial agents, 58(1), 106362.

Arriola Apelo, S. I., & Lamming, D. W. (2016). Rapamycin: an InhibiTOR of aging emerges from the soil of Easter Island. Journals of Gerontology Series A: Biomedical Sciences and Medical Sciences, 71(7), 841-849.

Bacchi, S., Palumbo, P., Sponta, A., & Coppolino, M. F. (2012). Clinical pharmacology of non-steroidal anti-inflammatory drugs: a review. Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry-Anti-Inflammatory and Anti-Allergy Agents), 11(1), 52-64.

Bardakji, Z., Jolivet, J., Langelier, Y., Besner, J. G., & Ayoub, J. (1986). 5-Fluorouracil-metronidazole combination therapy in metastatic colorectal cancer: clinical, pharmacokinetic and in vitro cytotoxicity studies. Cancer chemotherapy and pharmacology, 18, 140-144.

Barnett, C. F., & Machado, R. F. (2006). Sildenafil in the treatment of pulmonary hypertension. Vascular health and risk management, 2(4), 411-422.

Barradell, L. B., & Fitton, A. (1995). Artesunate: a review of its pharmacology and therapeutic efficacy in the treatment of malaria. Drugs, 50, 714-741.

Benfield, P., Heel, R. C., & Lewis, S. P. (1986). Fluoxetine: a review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in depressive illness. Drugs, 32, 481-508.

Benson, A. B., Venook, A. P., Cederquist, L., Chan, E., Chen, Y. J., Cooper, H. S., ... & Freedman-Cass, D. (2017). Colon cancer, version 1.2017, NCCN clinical practice guidelines in oncology. Journal of the National Comprehensive Cancer Network, 15(3), 370-398.

Berkovic, M. C., Mikulic, D., Bilic-Curcic, I., & Mrzljak, A. (2021). How far along are we in revealing the connection between metformin and colorectal cancer?. World journal of gastroenterology, 27(14), 1362.

Bernshteyn, M. A., & Masood, U. (2023). Pantoprazole.[Updated 2022 Jul 12]. StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing.

Bertagnolli, M. M., Eagle, C. J., Zauber, A. G., Redston, M., Solomon, S. D., Kim, K., ... & Hawk, E. T. (2006). Celecoxib for the prevention of sporadic colorectal adenomas. New England Journal of Medicine, 355(9), 873-884.

Bertolini, F., Sukhatme, V. P., & Bouche, G. (2015). Drug repurposing in oncology—patient and health systems opportunities. Nature reviews Clinical oncology, 12(12), 732-742.

Bock, F. J., & Tait, S. W. (2020). Mitochondria as multifaceted regulators of cell death. Nature reviews Molecular cell biology, 21(2), 85-100.

Booth, L., Roberts, J. L., Rais, R., Kirkwood, J., Avogadri-Connors, F., Cutler Jr, R. E., ... & Dent, P. (2018). [Neratinib+ Valproate] exposure permanently reduces ERBB1 and RAS expression in 4T1 mammary tumors and enhances M1 macrophage infiltration. Oncotarget, 9(5), 6062.

Brenner, H., & Kloor, M. (2014). Pox cP. colorectal cancer. Lancet, 383(9927), 1490-1502.

Brown, T., Sigurdson, E., Rogatko, A., & Broccoli, D. (2003). Telomerase inhibition using azidothymidine in the HT-29 colon cancer cell line. Annals of surgical oncology, 10, 910-915.

Bujanda, L., Cosme, A., Gil, I., & Arenas-Mirave, J. I. (2010). Malignant colorectal polyps. World journal of gastroenterology: WJG, 16(25), 3103.

Bullman, S., Pedamallu, C. S., Sicinska, E., Clancy, T. E., Zhang, X., Cai, D., ... & Meyerson, M. (2017). Analysis of Fusobacterium persistence and antibiotic response in colorectal cancer. Science, 358(6369), 1443-1448.

Burada, F., Nicoli, E. R., Ciurea, M. E., Uscatu, D. C., Ioana, M., & Gheonea, D. I. (2015). Autophagy in colorectal cancer: An important switch from physiology to pathology. World journal of gastrointestinal oncology, 7(11), 271.

Burlaka, A. P., Ganusevich, I. I., Vovk, A. V., Burlaka, A. A., Gafurov, M. R., & Lukin, S. N. (2018). Colorectal cancer and mitochondrial dysfunctions of the adjunct adipose tissues: a case study. BioMed research international, 2018.

Buse, J. B., Wexler, D. J., Tsapas, A., Rossing, P., Mingrone, G., Mathieu, C., ... & Davies, M. J. (2020). 2019 update to: management of hyperglycemia in type 2 diabetes, 2018. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes care, 43(2), 487-493.

Campoli-Richards, D. M., Monk, J. P., Price, A., Benfield, P., Todd, P. A., & Ward, A. (1988). Ciprofloxacin: a review of its antibacterial activity, pharmacokinetic properties and therapeutic use. Drugs, 35, 373-447.

Carella, A. M., Beltrami, G., Pica, G., Carella, A., & Catania, G. (2012). Clarithromycin potentiates tyrosine kinase inhibitor treatment in patients with resistant chronic myeloid leukemia. Leukemia & lymphoma, 53(7), 1409-1411.

Carrella, D., Manni, I., Tumaini, B., Dattilo, R., Papaccio, F., Mutarelli, M., ... & Cardone, L. (2016). Computational drugs repositioning identifies inhibitors of oncogenic PI3K/AKT/P70S6K-dependent pathways among FDA-approved compounds. Oncotarget, 7(37), 58743.

Chan, A. T., Ogino, S., & Fuchs, C. S. (2007). Aspirin and the risk of colorectal cancer in relation to the expression of COX-2. New England Journal of Medicine, 356(21), 2131-2142.

Chang, P. Y., Huang, W. Y., Lin, C. L., Huang, T. C., Wu, Y. Y., Chen, J. H., & Kao, C. H. (2015). Propranolol reduces cancer risk: a population-based cohort study. Medicine, 94(27), e1097.

Chatterjee, N., & Bivona, T. G. (2019). Polytherapy and targeted cancer drug resistance. Trends in cancer, 5(3), 170-182.

Chen, W., Mook Jr, R. A., Premont, R. T., & Wang, J. (2018). Niclosamide: Beyond an antihelminthic drug. Cellular signalling, 41, 89-96.

Childers, W. K. (2015). Interactions of the renin-angiotensin system in colorectal cancer and metastasis. International Journal of Colorectal Disease, 30(6), 749-752.

Chimenti, M. S., Sunzini, F., Fiorucci, L., Botti, E., Fonti, G. L., Conigliaro, P., ... & Giunta, A. (2018). Potential role of cytochrome c and tryptase in psoriasis and psoriatic arthritis pathogenesis: focus on resistance to apoptosis and oxidative stress. Frontiers in immunology, 9, 387495.

Cole, S. W., & Sood, A. K. (2012). Molecular pathways: beta-adrenergic signaling in cancer. Clinical cancer research, 18(5), 1201-1206.

Cunha, B. A., Sibley, C. M., & Ristuccia, A. M. (1982). Doxycycline. Therapeutic drug monitoring, 4(2), 115.

Dalal, A., Eskin-Schwartz, M., Mimouni, D., Ray, S., Days, W., Hodak, E., ... & Paul, M. (2017). Interventions for the prevention of recurrent erysipelas and cellulitis. Cochrane Database of Systematic Reviews, (6).

Dekker, E., Tanis, P. J., Vleugels, J. L., Kasi, P. M., & Wallace, M. (2019). Pure-amc. Lancet, 394, 1467-80.

Dickerman, B. A., García-Albéniz, X., Logan, R. W., Denaxas, S., & Hernán, M. A. (2020). Emulating a target trial in case-control designs: an application to statins and colorectal cancer. International journal of epidemiology, 49(5), 1637-1646.

Dingsdag, S. A., & Hunter, N. (2018). Metronidazole: an update on metabolism, structure–cytotoxicity and resistance mechanisms. Journal of Antimicrobial Chemotherapy, 73(2), 265-279.

Dinic, J., Efferth, T., García-Sosa, A. T., Grahovac, J., Padrón, J. M., Pajeva, I., ... & Tsakovska, I. (2020). Repurposing old drugs to fight multidrug resistant cancers. Drug Resistance Updates, 52, 100713.

Dovizio, M., Tacconelli, S., Sostres, C., Ricciotti, E., & Patrignani, P. (2012). Mechanistic and pharmacological issues of aspirin as an anticancer agent. Pharmaceuticals, 5(12), 1346-1371.

Drew, D. A., Cao, Y., & Chan, A. T. (2016). Aspirin and colorectal cancer: the promise of precision chemoprevention. Nature Reviews Cancer, 16(3), 173-186.

Duarte, D., & Vale, N. (2022). Combining repurposed drugs to treat colorectal cancer. Drug Discovery Today, 27(1), 165-184.

Dulai, P. S., Singh, S., Marquez, E., Khera, R., Prokop, L. J., Limburg, P. J., ... & Murad, M. H. (2016). Chemoprevention of colorectal cancer in individuals with previous colorectal neoplasia: systematic review and network meta-analysis. Bmj, 355.

Efferth, T., Sauerbrey, A., Olbrich, A., Gebhart, E., Rauch, P., Weber, H. O., ... & Funk, J. O. (2003). Molecular modes of action of artesunate in tumor cell lines. Molecular pharmacology, 64(2), 382-394.

El Zarif, T., Yibirin, M., De Oliveira-Gomes, D., Machaalani, M., Nawfal, R., Bittar, G., ... & Bitar, N. (2022). Overcoming therapy resistance in colon cancer by drug repurposing. Cancers, 14(9), 2105.

Esra’a, I. K., Ismail, W. W., Mhaidat, N. M., & Alqudah, M. A. (2021). Effect of metformin on irinotecan-induced cell cycle arrest in colorectal cancer cell lines HCT116 and SW480. International Journal of Health Sciences, 15(5), 34.

Esumi, H., Lu, J., Kurashima, Y., & Hanaoka, T. (2004). Antitumor activity of pyrvinium pamoate, 6-(dimethylamino)-2-[2-(2, 5-dimethyl-1-phenyl-1H-pyrrol-3-yl) ethenyl]-1-methyl-quinolinium pamoate salt, showing preferential cytotoxicity during glucose starvation. Cancer science, 95(8), 685-690.

Ezhilarasan, D. (2018). Herbal therapy for cancer: Clinical and experimental perspectives. In Understanding cancer therapies (pp. 129-166). CRC Press.

Fang, X., Hu, T., Yin, H., Yang, J., Tang, W., Hu, S., & Xu, X. (2017). Differences in telomerase activity and the effects of AZT in aneuploid and euploid cells in colon cancer. International Journal of Oncology, 51(2), 525-532.

Fink, H. A., Mac Donald, R., Rutks, I. R., Nelson, D. B., & Wilt, T. J. (2002). Sildenafil for male erectile dysfunction: a systematic review and meta-analysis. Archives of Internal Medicine, 162(12), 1349-1360.

Flory, J., & Lipska, K. (2019). Metformin in 2019. Jama, 321(19), 1926-1927.

Fluge, Ø., Gravdal, K., Carlsen, E., Vonen, B., Kjellevold, K., Refsum, S., ... & Dahl, O. (2009). Expression of EZH2 and Ki-67 in colorectal cancer and associations with treatment response and prognosis. British journal of cancer, 101(8), 1282-1289.

Fong, W., & To, K. K. (2019). Drug repurposing to overcome resistance to various therapies for colorectal cancer. Cellular and molecular life sciences, 76, 3383-3406.

Fontana, L., Cummings, N. E., Apelo, S. I. A., Neuman, J. C., Kasza, I., Schmidt, B. A., ... & Lamming, D. W. (2016). Decreased consumption of branched-chain amino acids improves metabolic health. Cell reports, 16(2), 520-530.

Freeman, C. D., Klutman, N. E., & Lamp, K. C. (1997). Metronidazole: a therapeutic review and update. Drugs, 54, 679-708.

Friedmann, I., Atmaca, A., Chow, K. U., Jäger, E., & Weidmann, E. (2006). Synergistic effects of valproic acid and mitomycin C in adenocarcinoma cell lines and fresh tumor cells of patients with colon cancer. Journal of chemotherapy, 18(4), 415-420.

Frouws, M. A., Bastiaannet, E., Langley, R. E., Chia, W. K., van Herk-Sukel, M. P. P., Lemmens, V. E. P. P., ... & Liefers, G. J. (2017). Effect of low-dose aspirin use on survival of patients with gastrointestinal malignancies; an observational study. British journal of cancer, 116(3), 405-413.

Gaedicke, S., Firat-Geier, E., Constantiniu, O., Lucchiari-Hartz, M., Freudenberg, M., Galanos, C., & Niedermann, G. (2002). Antitumor effect of the human immunodeficiency virus protease inhibitor ritonavir: induction of tumor-cell apoptosis associated with perturbation of proteasomal proteolysis. Cancer research, 62(23), 6901-6908.

Gogvadze, V., Orrenius, S., & Zhivotovsky, B. (2015). Analysis of mitochondrial dysfunction during cell death. Mitochondrial Medicine: Volume I, Probing Mitochondrial Function, 385-393.

Göttlicher, M., Minucci, S., Zhu, P., Krämer, O. H., Schimpf, A., Giavara, S., ... & Heinzel, T. (2001). Valproic acid defines a novel class of HDAC inhibitors inducing differentiation of transformed cells. The EMBO journal.

Grancher A, Michel P, Di Fiore F, Sefrioui D. Aspirine et cancer colorectal [Aspirin and colorectal cancer]. Bull Cancer. 2018 Feb;105(2):171-180. French. doi: 10.1016/j.bulcan.2017.09.013. Epub 2017 Nov 15. PMID: 29153543.

Grancher, A., Michel, P., Di Fiore, F., & Sefrioui, D. (2022). Colorectal cancer chemoprevention: is aspirin still in the game?. Cancer Biology & Therapy, 23(1), 446-461.

Gray, R. T., Coleman, H. G., Hughes, C., Murray, L. J., & Cardwell, C. R. (2018). Low-dose aspirin use and survival in colorectal cancer: results from a population-based cohort study. BMC cancer, 18, 1-8.

Hassan LEA, Al-Suede FS, Fadul SM, Abdul Majid AMS. (2018). Evaluation of antioxidant, antiangiogenic and antitumor properties of Anogeissus leiocarpus against colon cancer. Angiotherapy, 1(2), pages 056–066.Abate, M., Festa, A., Falco, M., Lombardi, A., Luce, A., Grimaldi, A.,& Misso, G. (2020, February). Mitochondria as playmakers of apoptosis, autophagy and senescence. In Seminars in cell & developmental biology (Vol. 98, pp. 139-153). Academic Press.

Hawk ET, Levin B. Colorectal cancer prevention. J Clin Oncol. 2005 Jan 10;23(2):378-91. doi: 10.1200/JCO.2005.08.097. PMID: 15637400.

He, K., Zheng, X., Li, M., Zhang, L., & Yu, J. (2016). mTOR inhibitors induce apoptosis in colon cancer cells via CHOP-dependent DR5 induction on 4E-BP1 dephosphorylation. Oncogene, 35(2), 148-157.

Hecht, M., Harrer, T., Büttner, M., Schwegler, M., Erber, S., Fietkau, R., & Distel, L. V. (2013). Cytotoxic effect of efavirenz is selective against cancer cells and associated with the cannabinoid system. Aids, 27(13), 2031-2040.

Hegazy, S. K., El-Azab, G. A., Zakaria, F., Mostafa, M. F., & El-Ghoneimy, R. A. (2022). Mebendazole; from an anti-parasitic drug to a promising candidate for drug repurposing in colorectal cancer. Life Sciences, 299, 120536.

Hellinger, R., & Gruber, C. W. (2019). Peptide-based protease inhibitors from plants. Drug discovery today, 24(9), 1877-1889.

Hicks, B. M., Murray, L. J., Powe, D. G., Hughes, C. M., & Cardwell, C. R. (2013). β-Blocker usage and colorectal cancer mortality: a nested case–control study in the UK Clinical Practice Research Datalink cohort. Annals of oncology, 24(12), 3100-3106.

Hijazi, M. A., Gessner, A., & El-Najjar, N. (2023). Repurposing of chronically used drugs in cancer therapy: a chance to grasp. Cancers, 15(12), 3199.

Hobby, G. L., Meyer, K., & Chaffee, E. (1942). Observations on the Mechanism of Action of Penicillin. Proceedings of the Society for Experimental Biology and Medicine, 50(2), 281-285.

Hradec, J. (2018). Pharmacological therapy for chronic heart failure. Vnitrni Lekarstvi, 64(9), 853-859.

Hu, F., Wu, Y., Liu, C., Zhu, Y., Ye, S., Xi, Y., ... & Bu, S. (2021). Penicillin disrupts mitochondrial function and induces autophagy in colorectal cancer cell lines. Oncology Letters, 22(4), 1-10.

Hu, S., Liu, L., Chang, E. B., Wang, J. Y., & Raufman, J. P. (2015). Butyrate inhibits pro-proliferative miR-92a by diminishing c-Myc-induced miR-17-92a cluster transcription in human colon cancer cells. Molecular cancer, 14, 1-15.

Hukezalie, K. R., Thumati, N. R., Coˆte, H. C., & Wong, J. M. (2012). In vitro and ex vivo inhibition of human telomerase by anti-HIV nucleoside reverse transcriptase inhibitors (NRTIs) but not by non-NRTIs. PLoS One, 7(11), e47505.

Ittaman, S. V., VanWormer, J. J., & Rezkalla, S. H. (2014). The role of aspirin in the prevention of cardiovascular disease. Clinical medicine & research, 12(3-4), 147-154.

Iwata, H., Sawada, R., Mizutani, S., & Yamanishi, Y. (2015). Systematic drug repositioning for a wide range of diseases with integrative analyses of phenotypic and molecular data. Journal of chemical information and modeling, 55(2), 446-459.

Jafri, M. A., Ansari, S. A., Alqahtani, M. H., & Shay, J. W. (2016). Roles of telomeres and telomerase in cancer, and advances in telomerase-targeted therapies. Genome medicine, 8, 1-18.

Jarada, T. N., Rokne, J. G., & Alhajj, R. (2020). A review of computational drug repositioning: strategies, approaches, opportunities, challenges, and directions. Journal of cheminformatics, 12, 1-23.

Jourdan, J. P., Bureau, R., Rochais, C., & Dallemagne, P. (2020). Drug repositioning: a brief overview. Journal of Pharmacy and Pharmacology, 72(9), 1145-1151.

Juneja, M., Kobelt, D., Walther, W., Voss, C., Smith, J., Specker, E., ... & Stein, U. (2017). Statin and rottlerin small-molecule inhibitors restrict colon cancer progression and metastasis via MACC1. PLoS Biology, 15(6), e2000784.

Júnior, A. D. C., Bragagnoli, A. C., Costa, F. O., & Carvalheira, J. B. C. (2021). Repurposing metformin for the treatment of gastrointestinal cancer. World journal of gastroenterology, 27(17), 1883.

Kamarudin, M. N. A., Sarker, M. M. R., Zhou, J. R., & Parhar, I. (2019). Metformin in colorectal cancer: molecular mechanism, preclinical and clinical aspects. Journal of Experimental & Clinical Cancer Research, 38(1), 491.

Kan, J. Y., Hsu, Y. L., Chen, Y. H., Chen, T. C., Wang, J. Y., & Kuo, P. L. (2013). Gemifloxacin, a fluoroquinolone antimicrobial drug, inhibits migration and invasion of human colon cancer cells. BioMed research international, 2013.

Kang, H. E., Seo, Y., Yun, J. S., Song, S. H., Han, D., Cho, E. S., ... & Kim, T. I. (2021). Metformin and niclosamide synergistically suppress Wnt and YAP in APC-mutated colorectal cancer. Cancers, 13(14), 3437.

Kannen, V., Bader, M., Sakita, J. Y., Uyemura, S. A., & Squire, J. A. (2020). The dual role of serotonin in colorectal cancer. Trends in Endocrinology & Metabolism, 31(8), 611-625.

Kannen, V., Hintzsche, H., Zanette, D. L., Silva Jr, W. A., Garcia, S. B., Waaga-Gasser, A. M., & Stopper, H. (2012). Antiproliferative effects of fluoxetine on colon cancer cells and in a colonic carcinogen mouse model. PLoS One, 7(11), e50043.

Kannen, V., Hintzsche, H., Zanette, D. L., Silva Jr, W. A., Garcia, S. B., Waaga-Gasser, A. M., & Stopper, H. (2012). Antiproliferative effects of fluoxetine on colon cancer cells and in a colonic carcinogen mouse model. PLoS One, 7(11), e50043.

Kedika, R., Patel, M., Sahdala, H. N. P., Mahgoub, A., Cipher, D., & Siddiqui, A. A. (2011). Long-term use of angiotensin converting enzyme inhibitors is associated with decreased incidence of advanced adenomatous colon polyps. Journal of clinical gastroenterology, 45(2), e12-e16.

Kee, J. Y., Han, Y. H., Mun, J. G., Um, J. Y., & Hong, S. H. (2018). Pharmacological effect of prohibited combination pair Panax ginseng and Veratrum nigrum on colorectal metastasis in vitro and in vivo. Journal of Ethnopharmacology, 220, 177-187.

Kim, S. H., Kim, S. C., & Ku, J. L. (2017). Metformin increases chemo-sensitivity via gene downregulation encoding DNA replication proteins in 5-Fu resistant colorectal cancer cells. Oncotarget, 8(34), 56546.

Kim, S. K., Guevarra, R. B., Kim, Y. T., Kwon, J., Kim, H., Cho, J. H., ... & Lee, J. H. (2019). Role of probiotics in human gut microbiome-associated diseases.

Kinloch-de Loës, S., Hirschel, B. J., Hoen, B., Cooper, D. A., Tindall, B., Carr, A., ... & Perrin, L. (1995). A controlled trial of zidovudine in primary human immunodeficiency virus infection. New England Journal of Medicine, 333(7), 408-413.

Koh, S. J., Kim, J. M., Kim, I. K., Kim, N., Jung, H. C., Song, I. S., & Kim, J. S. (2011). Fluoxetine inhibits NF-κB signaling in intestinal epithelial cells and ameliorates experimental colitis and colitis-associated colon cancer in mice. American Journal of Physiology-Gastrointestinal and Liver Physiology, 301(1), G9-G19.

Komatsu, S., Moriya, S., Che, X. F., Yokoyama, T., Kohno, N., & Miyazawa, K. (2013). Combined treatment with SAHA, bortezomib, and clarithromycin for concomitant targeting of aggresome formation and intracellular proteolytic pathways enhances ER stress-mediated cell death in breast cancer cells. Biochemical and biophysical research communications, 437(1), 41-47.

Kong, Z., Liu, R., & Cheng, Y. (2019). Artesunate alleviates liver fibrosis by regulating ferroptosis signaling pathway. Biomedicine & Pharmacotherapy, 109, 2043-2053.

Kopp, H. G., Placke, T., & Salih, H. R. (2009). Platelet-derived transforming growth factor-β down-regulates NKG2D thereby inhibiting natural killer cell antitumor reactivity. Cancer research, 69(19), 7775-7783.

Kovacs, E., Zorn, J. A., Huang, Y., Barros, T., & Kuriyan, J. (2015). A structural perspective on the regulation of the epidermal growth factor receptor. Annual review of biochemistry, 84, 739-764.

Krasteva, N., & Georgieva, M. (2022). Promising therapeutic strategies for colorectal cancer treatment based on nanomaterials. Pharmaceutics, 14(6), 1213.

Kubota, M., Shimizu, M., Sakai, H., Yasuda, Y., Ohno, T., Kochi, T., ... & Moriwaki, H. (2011). Renin–angiotensin system inhibitors suppress azoxymethane-induced colonic preneoplastic lesions in C57BL/KsJ-db/db obese mice. Biochemical and biophysical research communications, 410(1), 108-113.

Kumar, S. K., Callander, N. S., Adekola, K., Anderson, L., Baljevic, M., Campagnaro, E., ... & Kumar, R. (2020). Multiple myeloma, version 3.2021, NCCN clinical practice guidelines in oncology. Journal of the National Comprehensive Cancer Network, 18(12), 1685-1717.

Kumar, V. L., Verma, S., & Das, P. (2019). Artesunate suppresses inflammation and oxidative stress in a rat model of colorectal cancer. Drug Development Research, 80(8), 1089-1097.

Lacey, E. (1990). Mode of action of benzimidazoles. Parasitology today, 6(4), 112-115.

Lammers, T., Sofias, A. M., Van der Meel, R., Schiffelers, R., Storm, G., Tacke, F., ... & Metselaar, J. M. (2020). Dexamethasone nanomedicines for COVID-19. Nature nanotechnology, 15(8), 622-624.

Laudisi, F., Marônek, M., Di Grazia, A., Monteleone, G., & Stolfi, C. (2020). Repositioning of anthelmintic drugs for the treatment of cancers of the digestive system. International Journal of Molecular Sciences, 21(14), 4957.

Lawrie, T. A., Green, J. T., Beresford, M., Wedlake, L., Burden, S., Davidson, S. E., ... & Andreyev, H. J. N. (2018). Interventions to reduce acute and late adverse gastrointestinal effects of pelvic radiotherapy for primary pelvic cancers. Cochrane Database of Systematic Reviews, (1).

Lee, H. C., Chiu, W. C., Wang, T. N., Liao, Y. T., Chien, I. C., Lee, Y., ... & Chen, V. C. H. (2017). Antidepressants and colorectal cancer: A population-based nested case-control study. Journal of Affective Disorders, 207, 353-358.

Lennon, F. E., Mirzapoiazova, T., Mambetsariev, B., Poroyko, V. A., Salgia, R., Moss, J., & Singleton, P. A. (2014). The Mu opioid receptor promotes opioid and growth factor-induced proliferation, migration and Epithelial Mesenchymal Transition (EMT) in human lung cancer. PloS one, 9(3), e91577.

Liao, P., Song, K., Zhu, Z., Liu, Z., Zhang, W., Li, W., ... & He, Y. (2020). Propranolol suppresses the growth of colorectal cancer through simultaneously activating autologous CD8+ T cells and inhibiting tumor AKT/MAPK pathway. Clinical Pharmacology & Therapeutics, 108(3), 606-615.

Lin, J. L., Lin, J. X., Zheng, C. H., Li, P., Xie, J. W., Wang, J. B., ... & Huang, C. M. (2020). Relationship between aspirin use of esophageal, gastric and colorectal cancer patient survival: a meta-analysis. BMC cancer, 20, 1-15.

LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012–. PMID: 31643176.

LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012-. Nucleoside Analogues. [Updated 2020 May 1]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK548938/

Loulergue, P., Merad, M., Coriat, R., Ducreux, M., Planchard, D., Boige, V., ... & Mir, O. (2017). Safety of raltegravir-based antiretroviral therapy in HIV-infected patients receiving multi-kinase inhibitors. Investigational new drugs, 35, 247-249.

Lu, H., Zhang, H., Weng, M. L., Zhang, J., Jiang, N., Cata, J. P., ... & Miao, C. H. (2021). Morphine promotes tumorigenesis and cetuximab resistance via EGFR signaling activation in human colorectal cancer. Journal of Cellular Physiology, 236(6), 4445-4454.

Lutgendorf, S. K., Cole, S., Costanzo, E., Bradley, S., Coffin, J., Jabbari, S., ... & Sood, A. K. (2003). Stress-related mediators stimulate vascular endothelial growth factor secretion by two ovarian cancer cell lines. Clinical Cancer Research, 9(12), 4514-4521.

Ma, S., Song, W., Xu, Y., Si, X., Zhang, D., Lv, S., ... & Chen, X. (2020). Neutralizing tumor-promoting inflammation with polypeptide-dexamethasone conjugate for microenvironment modulation and colorectal cancer therapy. Biomaterials, 232, 119676.

Maher, D. P., Walia, D., & Heller, N. M. (2019). Suppression of human natural killer cells by different classes of opioids. Anesthesia & Analgesia, 128(5), 1013-1021.

Maione, A., Navaneethan, S. D., Graziano, G., Mitchell, R., Johnson, D., Mann, J. F., ... & Strippoli, G. F. (2011). Angiotensin-converting enzyme inhibitors, angiotensin receptor blockers and combined therapy in patients with micro-and macroalbuminuria and other cardiovascular risk factors: a systematic review of randomized controlled trials. Nephrology Dialysis Transplantation, 26(9), 2827-2847.

Markowska, A., Kaysiewicz, J., Markowska, J., & Huczynski, A. (2019). Doxycycline, salinomycin, monensin and ivermectin repositioned as cancer drugs. Bioorganic & Medicinal Chemistry Letters, 29(13), 1549-1554.

McAdam, B. F., Catella-Lawson, F., Mardini, I. A., Kapoor, S., Lawson, J. A., & FitzGerald, G. A. (1999). Systemic biosynthesis of prostacyclin by cyclooxygenase (COX)-2: the human pharmacology of a selective inhibitor of COX-2. Proceedings of the National Academy of Sciences, 96(1), 272-277.

Mezheyeuski, A., Hrynchyk, I., Karlberg, M., Portyanko, A., Egevad, L., Ragnhammar, P., ... & Östman, A. (2016). Image analysis-derived metrics of histomorphological complexity predicts prognosis and treatment response in stage II-III colon cancer. Scientific reports, 6(1), 36149.

Moffat, J. G., Vincent, F., Lee, J. A., Eder, J., & Prunotto, M. (2017). Opportunities and challenges in phenotypic drug discovery: an industry perspective. Nature reviews Drug discovery, 16(8), 531-543.

Mokarram, P., Albokashy, M., Zarghooni, M., Moosavi, M. A., Sepehri, Z., Chen, Q. M., ... & Ghavami, S. (2017). New frontiers in the treatment of colorectal cancer: Autophagy and the unfolded protein response as promising targets. Autophagy, 13(5), 781-819.

Mologni, L., Cleris, L., Magistroni, V., Piazza, R., Boschelli, F., Formelli, F., & Gambacorti-Passerini, C. (2009). Valproic acid enhances bosutinib cytotoxicity in colon cancer cells. International journal of cancer, 124(8), 1990-1996.

Momtazi-borojeni, A. A., Abdollahi, E., Ghasemi, F., Caraglia, M., & Sahebkar, A. (2018). The novel role of pyrvinium in cancer therapy. Journal of cellular physiology, 233(4), 2871-2881.

Moorthy, G. S., Lalley-Chareczko, L., Koenig, H. C., & Zuppa, A. F. (2020). Tenofovir urine assay to monitor adherence to HIV pre-exposure prophylaxis. Current clinical pharmacology, 15(2), 102-104.

Mühl, H., Paulukat, J., Höfler, S., Hellmuth, M., Franzen, R., & Pfeilschifter, J. (2004). The HIV protease inhibitor ritonavir synergizes with butyrate for induction of apoptotic cell death and mediates expression of heme oxygenase-1 in DLD-1 colon carcinoma cells. British journal of pharmacology, 143(7), 890-898.

Mussin, N., Oh, S. C., Lee, K. W., Park, M. Y., Seo, S., Yi, N. J., ... & Suh, K. S. (2017). Sirolimus and metformin synergistically inhibits colon cancer in vitro and in vivo. Journal of Korean Medical Science, 32(9), 1385.

Nakamura, M., Kikukawa, Y., Takeya, M., Mitsuya, H., & Hata, H. (2010). Clarithromycin attenuates autophagy in myeloma cells. International journal of oncology, 37(4), 815-820.

Ng, C. A. W., Jiang, A. A., Toh, E. M. S., Ng, C. H., Ong, Z. H., Peng, S., ... & Khoo, C. M. (2020). Metformin and colorectal cancer: a systematic review, meta-analysis and meta-regression. International journal of colorectal disease, 35, 1501-1512.

Nguyen, T. T., Ung, T. T., Li, S., Lian, S., Xia, Y., Park, S. Y., & Do Jung, Y. (2019). Metformin inhibits lithocholic acid-induced interleukin 8 upregulation in colorectal cancer cells by suppressing ROS production and NF-kB activity. Scientific reports, 9(1), 2003.

Nikolaou, M., Pavlopoulou, A., Georgakilas, A. G., & Kyrodimos, E. (2018). The challenge of drug resistance in cancer treatment: a current overview. Clinical & Experimental Metastasis, 35, 309-318.

Novellasdemunt, L., Antas, P., & Li, V. S. (2015). Targeting Wnt signaling in colorectal cancer. A review in the theme: cell signaling: proteins, pathways and mechanisms. American Journal of Physiology-Cell Physiology, 309(8), C511-C521.

Nowak-Sliwinska, P., Scapozza, L., & i Altaba, A. R. (2019). Drug repurposing in oncology: Compounds, pathways, phenotypes and computational approaches for colorectal cancer. Biochimica et Biophysica Acta (BBA)-Reviews on Cancer, 1871(2), 434-454.

Nuevo-Tapioles, C., Santacatterina, F., Stamatakis, K., Núñez de Arenas, C., Gómez de Cedrón, M., Formentini, L., & Cuezva, J. M. (2020). Coordinate β-adrenergic inhibition of mitochondrial activity and angiogenesis arrest tumor growth. Nature communications, 11(1), 3606.

Nygren, P., Fryknäs, M., Ågerup, B., & Larsson, R. (2013). Repositioning of the anthelmintic drug mebendazole for the treatment for colon cancer. Journal of cancer research and clinical oncology, 139, 2133-2140.

Ogrodowczyk, M., Dettlaff, K., & Jelinska, A. (2016). Beta-blockers: current state of knowledge and perspectives. Mini reviews in medicinal chemistry, 16(1), 40-54.

Okada, J., Matsumoto, S., Kaira, K., Saito, T., Yamada, E., Yokoo, H., ... & Yamada, M. (2018). Sodium glucose cotransporter 2 inhibition combined with cetuximab significantly reduced tumor size and carcinoembryonic antigen level in colon cancer metastatic to liver. Clinical Colorectal Cancer, 17(1), e45-e48.

Okada, J., Yamada, E., Saito, T., Yokoo, H., Osaki, A., Shimoda, Y., ... & Yamada, M. (2020). Dapagliflozin inhibits cell adhesion to collagen I and IV and increases ectodomain proteolytic cleavage of DDR1 by increasing ADAM10 activity. Molecules, 25(3), 495.

Onoda, T., Ono, T., Dhar, D. K., Yamanoi, A., & Nagasue, N. (2006). Tetracycline analogues (doxycycline and COL-3) induce caspase-dependent and-independent apoptosis in human colon cancer cells. International journal of cancer, 118(5), 1309-1315.

Onoda, T., Ono, T., Dhar, D. K., Yamanoi, A., Fujii, T., & Nagasue, N. (2004). Doxycycline inhibits cell proliferation and invasive potential: combination therapy with cyclooxygenase-2 inhibitor in human colorectal cancer cells. Journal of Laboratory and Clinical Medicine, 143(4), 207-216.

Osada, T., Chen, M., Yang, X. Y., Spasojevic, I., Vandeusen, J. B., Hsu, D., ... & Lyerly, H. K. (2011). Antihelminth compound niclosamide downregulates Wnt signaling and elicits antitumor responses in tumors with activating APC mutations. Cancer research, 71(12), 4172-4182.

Pacifici, G. M. (2016). Metabolism and pharmacokinetics of morphine in neonates: A review. Clinics, 71, 474-480.

Pai, R., Soreghan, B., Szabo, I. L., Pavelka, M., Baatar, D., & Tarnawski, A. S. (2002). Prostaglandin E2 transactivates EGF receptor: a novel mechanism for promoting colon cancer growth and gastrointestinal hypertrophy. Nature medicine, 8(3), 289-293.

Pajonk, F., Himmelsbach, J., Riess, K., Sommer, A., & McBride, W. H. (2002). The human immunodeficiency virus (HIV)-1 protease inhibitor saquinavir inhibits proteasome function and causes apoptosis and radiosensitization in non-HIV-associated human cancer cells. Cancer research, 62(18), 5230-5235.

Patel, M. M., & Patel, B. M. (2018). Repurposing of sodium valproate in colon cancer associated with diabetes mellitus: Role of HDAC inhibition. European Journal of Pharmaceutical Sciences, 121, 188-199.

Pati, S., Pelser, C. B., Dufraine, J., Bryant, J. L., Reitz Jr, M. S., & Weichold, F. F. (2002). Antitumorigenic effects of HIV protease inhibitor ritonavir: inhibition of Kaposi sarcoma. Blood, The Journal of the American Society of Hematology, 99(10), 3771-3779.

Petersen, J. S., & Baird, S. K. (2021). Treatment of breast and colon cancer cell lines with anti-helmintic benzimidazoles mebendazole or albendazole results in selective apoptotic cell death. Journal of Cancer Research and Clinical Oncology, 147, 2945-2953.

Petroni, G., Bagni, G., Iorio, J., Duranti, C., Lottini, T., Stefanini, M., ... & Arcangeli, A. (2020). Clarithromycin inhibits autophagy in colorectal cancer by regulating the hERG1 potassium channel interaction with PI3K. Cell death & disease, 11(3), 161.

Pistritto, G., Trisciuoglio, D., Ceci, C., Garufi, A., & D'Orazi, G. (2016). Apoptosis as anticancer mechanism: function and dysfunction of its modulators and targeted therapeutic strategies. Aging (albany NY), 8(4), 603.

Poynter, J. N., Gruber, S. B., Higgins, P. D., Almog, R., Bonner, J. D., Rennert, H. S., ... & Rennert, G. (2005). Statins and the risk of colorectal cancer. New England Journal of Medicine, 352(21), 2184-2192.

Qi, J. H., Wei, J. N., Zhang, Z. J., Dong, L., Zhang, L., Mao, Y. Y., ... & Bai, W. Q. (2021). A Meta-analysis on association between statins and colorectal cancer. Zhonghua liu Xing Bing xue za zhi= Zhonghua Liuxingbingxue Zazhi, 42(2), 343-350.

Qiao, X., Wang, X., Shang, Y., Li, Y., & Chen, S. Z. (2018). Azithromycin enhances anticancer activity of TRAIL by inhibiting autophagy and up-regulating the protein levels of DR4/5 in colon cancer cells in vitro and in vivo. Cancer Communications, 38, 1-13.

Raynal, N. J. M., Da Costa, E. M., Lee, J. T., Gharibyan, V., Ahmed, S., Zhang, H., ... & Issa, J. P. J. (2017). Repositioning FDA-approved drugs in combination with epigenetic drugs to reprogram colon cancer epigenome. Molecular cancer therapeutics, 16(2), 397-407.

Rebuzzi, S. E., Pesola, G., Martelli, V., & Sobrero, A. F. (2020). Adjuvant chemotherapy for stage II colon cancer. Cancers, 12(9), 2584.

Rissardo, J. P., Caprara, A. L. F., & Durante, Í. (2021). Valproate-associated movement disorder: a literature review. Prague Medical Report, 122(3), 140-180.

Rocha, G. Z., Dias, M. M., Ropelle, E. R., Osório-Costa, F., Rossato, F. A., Vercesi, A. E., ... & Carvalheira, J. B. (2011). Metformin amplifies chemotherapy-induced AMPK activation and antitumoral growth. Clinical cancer research, 17(12), 3993-4005.

Saber, M. M., Galal, M. A., Ain-Shoka, A. A., & Shouman, S. A. (2016). Combination of metformin and 5-aminosalicylic acid cooperates to decrease proliferation and induce apoptosis in colorectal cancer cell lines. BMC cancer, 16, 1-12.

Sack, U., Walther, W., Scudiero, D., Selby, M., Kobelt, D., Lemm, M., ... & Stein, U. (2011). Novel effect of antihelminthic Niclosamide on S100A4-mediated metastatic progression in colon cancer. Journal of the National Cancer Institute, 103(13), 1018-1036.

Saito, T., Okada, S., Yamada, E., Shimoda, Y., Osaki, A., Tagaya, Y., ... & Yamada, M. (2015). Effect of dapagliflozin on colon cancer cell [Rapid Communication]. Endocrine Journal, 62(12), 1133-1137.

Sanford, S. L., Welfer, G. A., Freudenthal, B. D., & Opresko, P. L. (2020). Mechanisms of telomerase inhibition by oxidized and therapeutic dNTPs. Nature Communications, 11(1), 5288.

Schafranek, L., Leclercq, T. M., White, D. L., & Hughes, T. P. (2013). Clarithromycin enhances dasatinib-induced cell death in chronic myeloid leukemia cells, by inhibition of late stage autophagy. Leukemia & lymphoma, 54(1), 198-201.

Schjerning, A. M., McGettigan, P., & Gislason, G. (2020). Cardiovascular effects and safety of (non-aspirin) NSAIDs. Nature Reviews Cardiology, 17(9), 574-584.

Sehgal, S. N. (2003, May). Sirolimus: its discovery, biological properties, and mechanism of action. In Transplantation proceedings (Vol. 35, No. 3, pp. S7-S14). Elsevier.

Sekandarzad, M. W., van Zundert, A. A., Lirk, P. B., Doornebal, C. W., & Hollmann, M. W. (2017). Perioperative anesthesia care and tumor progression. Anesthesia & Analgesia, 124(5), 1697-1708.

Sheng, J., Sun, H., Yu, F. B., Li, B., Zhang, Y., & Zhu, Y. T. (2020). The role of cyclooxygenase-2 in colorectal cancer. International journal of medical sciences, 17(8), 1095.

Sherif, D. A., Makled, M. N., & Suddek, G. M. (2021). The HIV reverse transcriptase inhibitor Tenofovir suppressed DMH/HFD-induced colorectal cancer in Wistar rats. Fundamental & Clinical Pharmacology, 35(6), 940-954.

Shi, S., Zheng, H. C., & Zhang, Z. G. (2020). Roles of Fascin mRNA expression in colorectal cancer: Meta-analysis and bioinformatics analysis. Molecular and Clinical Oncology, 13(2), 119-128.

Siegel, R. L., Miller, K. D., Fuchs, H. E., & Jemal, A. (2021). Cancer statistics, 2021. Ca Cancer J Clin, 71(1), 7-33.

Singleton, P. A., Moss, J., Karp, D. D., Atkins, J. T., & Janku, F. (2015). The mu opioid receptor: a new target for cancer therapy?. Cancer, 121(16), 2681-2688.

Slattery, M. L., Herrick, J. S., Lundgreen, A., Fitzpatrick, F. A., Curtin, K., & Wolff, R. K. (2010). Genetic variation in a metabolic signaling pathway and colon and rectal cancer risk: mTOR, PTEN, STK11, RPKAA1, PRKAG2, TSC1, TSC2, PI3K and Akt1. Carcinogenesis, 31(9), 1604-1611.

Sood, A. K., Armaiz-Pena, G. N., Halder, J., Nick, A. M., Stone, R. L., Hu, W., ... & Lutgendorf, S. K. (2010). Adrenergic modulation of focal adhesion kinase protects human ovarian cancer cells from anoikis. The Journal of clinical investigation, 120(5), 1515-1523.

Sood, A. K., Bhatty, R., Kamat, A. A., Landen, C. N., Han, L., Thaker, P. H., ... & Cole, S. W. (2006). Stress hormone–mediated invasion of ovarian cancer cells. Clinical Cancer Research, 12(2), 369-375.

Sorkin, E. M., Clissold, S. P., & Brogden, R. N. (1985). Nifedipine: a review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy, in ischaemic heart disease, hypertension and related cardiovascular disorders. Drugs, 30, 182-274.

Steinbach, G., Lynch, P. M., Phillips, R. K., Wallace, M. H., Hawk, E., Gordon, G. B., ... & Kelloff, G. (2000). The effect of celecoxib, a cyclooxygenase-2 inhibitor, in familial adenomatous polyposis. New England Journal of Medicine, 342(26), 1946-1952.

Suehiro, Y., Takemoto, Y., Nishimoto, A., Ueno, K., Shirasawa, B., Tanaka, T., ... & Hamano, K. (2018). Dclk1 inhibition cancels 5-FU-induced cell-cycle arrest and decreases cell survival in colorectal cancer. Anticancer Research, 38(11), 6225-6230.

Sung, H., Ferlay, J., Siegel, R. L., Laversanne, M., Soerjomataram, I., Jemal, A., & Bray, F. (2021). Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: a cancer journal for clinicians, 71(3), 209-249.

Talha B, Dhamoon AS. Ritonavir. 2023 Aug 8. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan–. PMID: 31335032

Tampakis, A., Tampaki, E. C., Nonni, A., Kostakis, I. D., Posabella, A., Kontzoglou, K., ... & Nikiteas, N. (2021). High fascin-1 expression in colorectal cancer identifies patients at high risk for early disease recurrence and associated mortality. BMC cancer, 21, 1-10.

Tanaka, H., Hino, H., Moriya, S., Kazama, H., Miyazaki, M., Takano, N., ... & Miyazawa, K. (2020). Comparison of autophagy inducibility in various tyrosine kinase inhibitors and their enhanced cytotoxicity via inhibition of autophagy in cancer cells in combined treatment with azithromycin. Biochemistry and biophysics reports, 22, 100750.

Thaker, P. H., Han, L. Y., Kamat, A. A., Arevalo, J. M., Takahashi, R., Lu, C., ... & Sood, A. K. (2006). Chronic stress promotes tumor growth and angiogenesis in a mouse model of ovarian carcinoma. Nature medicine, 12(8), 939-944.

Thun, M. J., Jacobs, E. J., & Patrono, C. (2012). The role of aspirin in cancer prevention. Nature reviews Clinical oncology, 9(5), 259-267.

Toriyama, K., Takano, N., Kokuba, H., Kazama, H., Moriya, S., Hiramoto, M., ... & Miyazawa, K. (2021). Azithromycin enhances the cytotoxicity of DNA-damaging drugs via lysosomal membrane permeabilization in lung cancer cells. Cancer Science, 112(8), 3324-3337.

Toschi, E., Sgadari, C., Malavasi, L., Bacigalupo, I., Chiozzini, C., Carlei, D., ... & Ensoli, B. (2011). Human immunodeficiency virus protease inhibitors reduce the growth of human tumors via a proteasome-independent block of angiogenesis and matrix metalloproteinases. International journal of cancer, 128(1), 82-93.

Tsujii, M., & DuBois, R. N. (1995). Alterations in cellular adhesion and apoptosis in epithelial cells overexpressing prostaglandin endoperoxide synthase 2. Cell, 83(3), 493-501.

Van der Jeught, K., Xu, H. C., Li, Y. J., Lu, X. B., & Ji, G. (2018). Drug resistance and new therapies in colorectal cancer. World journal of gastroenterology, 24(34), 3834.

Verma, S. K., Das, A. K., Gantait, S., Kumar, V., & Gurel, E. (2019). Applications of carbon nanomaterials in the plant system: a perspective view on the pros and cons. Science of the Total Environment, 667, 485-499.

Verma, S., Das, P., & Kumar, V. L. (2017). Chemoprevention by artesunate in a preclinical model of colorectal cancer involves down regulation of β-catenin, suppression of angiogenesis, cellular proliferation and induction of apoptosis. Chemico-biological interactions, 278, 84-91.

Vermunt, M. A., van der Heijden, L. T., Hendrikx, J. J., Schinkel, A. H., de Weger, V. A., van der Putten, E., ... & Beijnen, J. H. (2021). Pharmacokinetics of docetaxel and ritonavir after oral administration of ModraDoc006/r in patients with prostate cancer versus patients with other advanced solid tumours. Cancer Chemotherapy and Pharmacology, 87, 855-869.

Verschoor, Y. L., van den Berg, J., Beets, G., Sikorska, K., Aalbers, A., Van Lent, A., ... & Chalabi, M. (2022). Neoadjuvant nivolumab, ipilimumab, and celecoxib in MMR-proficient and MMR-deficient colon cancers: Final clinical analysis of the NICHE study.

Vial, G., Detaille, D., & Guigas, B. (2019). Role of mitochondria in the mechanism (s) of action of metformin. Frontiers in endocrinology, 10, 442419.

Vidali, S., Aminzadeh, S., Lambert, B., Rutherford, T., Sperl, W., Kofler, B., & Feichtinger, R. G. (2015). Mitochondria: The ketogenic diet—A metabolism-based therapy. The international journal of biochemistry & cell biology, 63, 55-59.

Wang, Y., Liu, Y., Lu, J., Zhang, P., Wang, Y., Xu, Y., ... & Wei, G. (2013). Rapamycin inhibits FBXW7 loss-induced epithelial–mesenchymal transition and cancer stem cell-like characteristics in colorectal cancer cells. Biochemical and biophysical research communications, 434(2), 352-356.

Wassner, C., Bradley, N., & Lee, Y. (2020). A review and clinical understanding of tenofovir: tenofovir disoproxil fumarate versus tenofovir alafenamide. Journal of the International Association of Providers of AIDS Care (JIAPAC), 19, 2325958220919231.

Wild, C., Weiderpass, E., & Stewart, B. W. (Eds.). (2020). World cancer report: cancer research for cancer prevention. International Agency for Research on Cancer.

Williamson, T., Bai, R. Y., Staedtke, V., Huso, D., & Riggins, G. J. (2016). Mebendazole and a non-steroidal anti-inflammatory combine to reduce tumor initiation in a colon cancer preclinical model. Oncotarget, 7(42), 68571.

Wu, L., Lin, W., Liao, Q., Wang, H., Lin, C., Tang, L., ... & Zhao, L. (2020). Calcium channel blocker nifedipine suppresses colorectal cancer progression and immune escape by preventing NFAT2 nuclear translocation. Cell reports, 33(4).

Wu, Y., Xiab, R., Dai, C., Yan, S., Xie, T., Liu, B., ... & Huang, Q. Dexamethasone inhibits the proliferation of tumor cells. Cancer Manag Res [Internet]. 2019 Feb; 11: 1141–1154.[cited 2019 Apr 4].

Xie, L., Zhu, G., Shang, J., Chen, X., Zhang, C., Ji, X., ... & Wei, Y. (2021). An overview on the biological activity and anti-cancer mechanism of lovastatin. Cellular Signalling, 87, 110122.

Xu, L., Xia, H., Ni, D., Hu, Y., Liu, J., Qin, Y., ... & Xie, Y. (2020). High-dose dexamethasone manipulates the tumor microenvironment and internal metabolic pathways in anti-tumor progression. International Journal of Molecular Sciences, 21(5), 1846.

Xu, X. T., Hu, W. T., Zhou, J. Y., & Tu, Y. (2017). Celecoxib enhances the radiosensitivity of HCT116 cells in a COX-2 independent manner by up-regulating BCCIP. American journal of translational research, 9(3), 1088.

Xu, X., Wang, J., Han, K., Li, S., Xu, F., & Yang, Y. (2018). Antimalarial drug mefloquine inhibits nuclear factor kappa B signaling and induces apoptosis in colorectal cancer cells. Cancer science, 109(4), 1220-1229.

Xue, H., Li, J., Xie, H., & Wang, Y. (2018). Review of drug repositioning approaches and resources. International journal of biological sciences, 14(10), 1232.

Yang, J. L., & Friedlander, M. L. (2001). Effect of nifedipine in metastatic colon cancer with DNA mismatch repair gene defect. The Lancet, 357(9270), 1767-1768.

Yang, Y., Weng, W., Peng, J., Hong, L., Yang, L., Toiyama, Y., ... & Ma, Y. (2017). Fusobacterium nucleatum increases proliferation of colorectal cancer cells and tumor development in mice by activating toll-like receptor 4 signaling to nuclear factor− κB, and up-regulating expression of microRNA-21. Gastroenterology, 152(4), 851-866.

Yano, A., Fujii, Y., Iwai, A., Kageyama, Y., & Kihara, K. (2006). Glucocorticoids suppress tumor angiogenesis and in vivo growth of prostate cancer cells. Clinical Cancer Research, 12(10), 3003-3009.

Yatsunami, J., Turuta, N., Wakamatsu, K., Hara, N., & Hayashi, S. I. (1997). Clarithromycin is a potent inhibitor of tumor-induced angiogenesis. Research in experimental medicine, 197, 189-197.

Zeng, X., Liu, L., Zheng, M., Sun, H., Xiao, J., Lu, T., ... & Duan, Q. (2016). Pantoprazole, an FDA-approved proton-pump inhibitor, suppresses colorectal cancer growth by targeting T-cell-originated protein kinase. Oncotarget, 7(16), 22460.

Zhanel, G. G., Fontaine, S., Adam, H., Schurek, K., Mayer, M., Noreddin, A. M., ... & Hoban, D. J. (2006). A review of new fluoroquinolones: focus on their use in respiratory tract infections. Treatments in respiratory medicine, 5, 437-465.

Zhang, L., Liu, C., Jiang, Q., & Yin, Y. (2021). Butyrate in energy metabolism: there is still more to learn. Trends in Endocrinology & Metabolism, 32(3), 159-169.

Zhang, Z., Ji, J., & Liu, H. (2021). Drug repurposing in oncology: Current evidence and future direction. Current Medicinal Chemistry, 28(11), 2175-2194.

Zheng, W., Hu, J., Lv, Y., Bai, B., Shan, L., Chen, K., ... & Zhu, H. (2021). Pyrvinium pamoate inhibits cell proliferation through ROS-mediated AKT-dependent signaling pathway in colorectal cancer. Medical Oncology, 38, 1-9.

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