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El Zarif, T.; Bahmad, H.; , .; De Oliveira Gomes, D.; Machaalani, M.; Nawfal, R.; Bittar, G. Repurposing Approved Drugs in Colon Cancer. Encyclopedia. Available online: https://encyclopedia.pub/entry/23028 (accessed on 16 November 2024).
El Zarif T, Bahmad H,  , De Oliveira Gomes D, Machaalani M, Nawfal R, et al. Repurposing Approved Drugs in Colon Cancer. Encyclopedia. Available at: https://encyclopedia.pub/entry/23028. Accessed November 16, 2024.
El Zarif, Talal, Hisham Bahmad,  , Diana De Oliveira Gomes, Marc Machaalani, Rashad Nawfal, Gianfranco Bittar. "Repurposing Approved Drugs in Colon Cancer" Encyclopedia, https://encyclopedia.pub/entry/23028 (accessed November 16, 2024).
El Zarif, T., Bahmad, H., , ., De Oliveira Gomes, D., Machaalani, M., Nawfal, R., & Bittar, G. (2022, May 18). Repurposing Approved Drugs in Colon Cancer. In Encyclopedia. https://encyclopedia.pub/entry/23028
El Zarif, Talal, et al. "Repurposing Approved Drugs in Colon Cancer." Encyclopedia. Web. 18 May, 2022.
Repurposing Approved Drugs in Colon Cancer
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This entry is adapted from the peer-reviewed paper 10.3390/cancers14092105

Despite improvements in standardized screening methods and the development of promising therapies for colorectal cancer (CRC), survival rates are still low. Drug repurposing offers an affordable solution to achieve new indications for previously approved drugs that could play a protagonist or adjuvant role in the treatment of CRC. 

colorectal cancer therapy resistance drug repurposing

1. Repurposing Approved Drugs in Colon Cancer

Drug repurposing or repositioning involves using approved drugs for conditions different from their original indication [1][2][3]. Several drugs have acquired additional use in the past years and have been reintroduced into practice fueled by this phenomenon. For instance, thalidomide, discontinued from its original use as an antiemetic, is currently used for multiple myeloma [4] and moderate to severe erythema nodosum leprosum [5]. Another example is Sildenafil which preserves both its primary indication for erectile dysfunction [6] and repurposed indication as a treatment option for idiopathic pulmonary hypertension [7].
Drug repurposing has regained a significant role as a convenient, fast, and relatively safe drug development strategy. New drug development usually takes around 10–15 years on average [8], with a success rate reported from 2 to 10% [9][10]. According to the U.S. Food and Drug Administration (FDA), as of 2018, the compound percentage of drugs reaching stage 4 clinical trials was around 6% [11]. Drug repurposing offers significantly shorter development times and lower investments described as 160 million times lower, particularly costs regarding safety testing, molecular characterization, safety profiling, and initial marketing. It leverages known genetic, pharmacodynamic, pharmacokinetic, and adverse effect profiles, usually bypassing stage 1 clinical trials [12]. Therefore, this approach represents a more cost-efficient, expedited, and less risky strategy than traditional drug development [9].
Many successful reintroductions and alternative indications second repurposing as a feasible option in many areas of medicine. Aspirin, for example, has acquired a wide range of indications, ranging from acutely therapeutic to prolonged preventative ones [2][13]. The cardiovascular field further illustrates this diversity with the recent supportive evidence of SGLT-2 inhibitors, initially approved for hyperglycemia management, for heart failure management regardless of the patients’ ejection fraction and notwithstanding their diabetes status [14][15][16][17]. Therapeutics for Alzheimer’s disease have been highly reliant on this strategy. Since memantine in 2003, no new drugs had been approved until the FDA granted the recent fast track concession for aducanumab in 2021 [2][18]. As of 2017, approximately 27 FDA-approved drugs were being evaluated for Alzheimer’s disease in stages 1–3 clinical trials [2].
Oncology has also gained benefits from drug repurposing. Estimation is that 5% of the anticancer drugs entering phase 1 clinical trials are eventually approved [19]. Certain calcium channels blockers such as felodipine and amlodipine besylate undermine filopodia stability in cancer cells, decreasing the likelihood of progression, invasion, and metastasis [20]. Metformin, classically an antidiabetic drug, has been described to decrease tumor growth. Although metabolic reprogramming halting oxidative phosphorylation and multi-targeted mTOR inhibition have hypothesized metformin’s antitumoral activity, precise mechanisms remain obscure [9][21][22].
The benefits of drug repurposing are evident after their serendipitous discovery and raise interest in predictive tools to optimize outcomes. Many approaches group together into either experimental or computational models [12][23]. The former usually involves either in vitro analysis measuring affinity and interaction stability, also called binding assays, or combined in vitro/in vivo models using compound libraries to test for cellular lineage changes, known as the phenotypic model. The phenotypic approach aims to reproduce diseases in an experimental cellular environment and relies on known compound libraries to test and characterize cellular responses [12]. Alternatively, known compounds have been assessed using in silico models stemming from structure-based principles: direct molecular docking, inverse molecular docking, and receptor-based pharmacophore searching [24]. Drug-based strategies use established drug information such as pharmacodynamics, biochemical, adverse effect profiles, and genomic data to determine potential alternative uses. Transcriptomics data are especially valuable to depict deviant cellular responses to diverse pathologic states, notably those with solid genetic pathomechanisms. Conversely, knowledge-based strategies use well-characterized molecular disease mechanisms to depict candidates for drug repurposing [23].
Large genetic and disease datasets are becoming publicly available, and computational tools for processing massive data are evolving accordingly. Computational-based drug repurposing uses data mining, machine learning, and network analysis to distill large datasets involving disease-specific transcriptomics, proteomics, drug efficacy, responses, and even clinical variables [23]. This information provides insight into complex biologic processes such as epigenetic regulation in cancer cells. Furthermore, drug repurposing approaches may be used for epigenetic reprogramming of cancer cells to increase susceptibility via differential transcriptome expressions. A study characterized 45 FDA-approved drugs yielding synergistic activity with histone deacetylating agents and methylation inhibitors. Additionally, they characterized 85 FDA-approved medications that antagonized the action of these drug families, thwarting favorable responses in colon cancer cells. Altogether, these findings illustrate the benefits and complexity of drug repurposing to design personalized and highly effective treatment plans that account for previously unknown drug interactions [25].

2. Anti-Hypertensives and Anti-Arrhythmic Drugs

Angiotensin I converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) are commonly used drugs that have life-prolonging effects on patients treated for several diseases including but not limited to hypertension and heart failure [26]. An in vivo study by Kubota et al. suggested that both ACEIs and ARBs suppress colitis-induced CRC by decreasing chronic inflammation and oxidative stress in obese mice [27]. In another study by Kedika et al., patients who had one or more histologically confirmed adenomatous polyps on an index colonoscopy and received lisinopril—an ACEI—had a 41% reduction in the risk of developing similar polyps over the next 3–5 years [28].
Beta blockers (BB) are class II antiarrhythmic drugs used primarily to treat cardiovascular diseases and many other conditions [29]. In a study by Tapioles et al., Nebivolol was shown to selectively inhibit mitochondrial respiration in an HCT-116 colon cancer cell line by decreasing the activity of complex I of the respiratory chain and restraining the growth of colon cancer cells, hinting towards a repurposing potential for this drug in colon cancer [30]. Furthermore, Engineer et al. demonstrated that the combination of ACEI/ARB with BB was associated with increased survival, decreased hospitalization, and decreased tumor progression in advanced CRC [31].

3. Nonsteroidal Anti-Inflammatory Drugs

Nonsteroidal anti-inflammatory drugs (NSAIDs) employ their anti-inflammatory, analgesic, and antipyretic properties by inhibiting the cyclooxygenase (COX) enzymes [32]. COX-2 overexpression is a major risk factor for the development of CRC [33]. The therapeutic effect of aspirin in CRC can be explained by inhibition of COX-2 as well as the c-MYC transcription factor [34][35]. Furthermore, aspirin blocks platelet activity which is implicated in cancer metastasis and immune evasion [36]. However, Chan et al. argued that aspirin must be used for more than 10 years to achieve a statistically significant reduction in COX-2 positive cancer [37].
Celecoxib works by selectively and reversibly inhibiting COX-2, and thus acts to decrease inflammation and pain without affecting platelets [38]. Many studies concluded that celecoxib increases radiosensitization of CRC cells [39][40]. Celecoxib also affects p53 by regulating the expression of p21 and CyclinD1 in a COX-2-independent manner, by upregulating BCCIP, increasing radiosensitivity in the HCT116 CRC cell line [41]. A randomized controlled trial by Bertagnolli et al. showed that celecoxib was effective for the secondary prevention of colorectal adenomas and decreased the cumulative incidence of adenomas after 3 years from 60.7% in the placebo arm to 43.2% in patients receiving 200 mg of celecoxib twice daily [42].

4. Anti-Hyperlipidemic Drugs

Statins markedly inhibit HMG-CoA reductase, the enzyme that controls the rate-limiting step in the cholesterol synthesis pathway in the liver [43]. Remarkably, in a large study including 1953 patients with CRC and 2015 controls, the use of statins for at least 5 years was associated with a significantly reduced relative risk of developing CRC (odds ratio (OR) = 0.50; 95% confidence interval (CI), 0.40–0.63) [44]. In vivo, lovastatin was shown to restrict cancer progression and metastasis formation by inhibiting MACC1 [45]. In a large meta-analysis including a total of 31 studies and involving more than 1.6 million subjects, statins were shown to have a moderate protective effect against developing CRC [46].

5. Anti-Diabetic Drugs

Metformin, an oral anti-diabetic medication used for type 2 diabetes mellitus, is a biguanide drug that increases insulin sensitivity, decreases intestinal absorption of glucose, and decreases its production by the liver [47]. Previous studies have shown a protective effect of metformin in CRC risk and prognosis [48][49]. The current understanding is that metformin inhibits the mammalian target of rapamycin (mTOR) pathway which plays a central role in CRC cell growth and proliferation [50]. Furthermore, metformin downregulates IGF receptor activation through decreasing insulin and insulin growth factor, resulting in decreased proliferation in colorectal neoplasia [51][52]. Inhibition of mTOR is achieved through inhibition of mitochondrial mammalian respiratory chain complex I followed by activation of liver kinase B1 and downstream target Adenosine monophosphate-activated protein kinase (AMPK) [53][54]. Other research has shown that metformin, through modulation of oxidative stress and nuclear factor-κB (NF-κB) inflammatory responses would induce apoptosis in CRC cell lines [55][56]. Metformin may also increase sensitivity of cancer cell lines to chemotherapeutic agents such as 5-Fluorouracil, irinotecan, and paclitaxel [57][58][59].
Dapagliflozin, another oral antihyperglycemic medication used for type 2 diabetes mellitus works by inhibiting the sodium/glucose cotransporter 2 (SGLT2) in the proximal tubules of the kidney [60]. Dapagliflozin decreases the adhesion of CRC cells by affecting cellular interaction with Collagen types I and IV through activating ADAM10, which subsequently causes a loss in the full-length DDR1 [61]. DDR1 binding to Collagens I and IV is necessary to stimulate cell–collagen interactions [62]. Dapagliflozin also decreases colon cell proliferation by increasing Erk phosphorylation in the HCT116 human colon cancer cell line [63]. In a case report by Okada et al., SGLT2 inhibition in combination with the EGFR inhibitor, cetuximab, reduced both tumor size and carcinoembryonic antigen (CEA) levels in CRC with liver metastasis [64].

6. Anti-Helminthic Drugs

Mebendazole is a broad spectrum benzimidazole that inhibits microtubule synthesis by blocking tubulin polymerization [65]. Mebendazole has cytotoxic activity against different CRC cell lines such as HCT-116, RKO, HT-29, HT-8, and SW626 [66][67]. Nygren and Larsson reported that mebendazole induced remission of metastatic lesions in a patient with refractory metastatic CRC [68]. Another study carried out on mice with a constitutional mutation in the Adenomatous polyposis coli (APC) gene showed that the combination of mebendazole and sulindac (an NSAID) decreased both the number and size of intestinal microadenomas by inhibiting MYC and COX-2 pathways, angiogenesis, and the release of pro-tumorigenic cytokines [69].
Niclosamide is a salicylamide derivative that acts by uncoupling oxidative phosphorylation and regulating different signaling pathways [70]. Niclosamide downregulated the Wnt/β-catenin cascade, which is aberrantly activated in 80% of sporadic CRC [71], in both in vitro and in vivo studies [72] and resulted in decreased proliferation in multiple human CRC cell lines such as HCT-116, Caco2, and HT-29 [73], possibly via the induction of autophagy [74]. Furthermore, a recent study by Kang et al. demonstrated that niclosamide could be combined with metformin to synergistically inhibit APC-mutant CRC by suppressing Wnt and YAP [75].

7. Anti-Retroviral Drugs

Tenofovir is a nucleoside antiretroviral drug that acts by inhibiting the reverse transcriptase enzyme [76]. Tenofovir also inhibits the activity of human telomerase [77], a crucial enzyme for tumorigenesis and cancer proliferation, whose inhibition represents a promising therapeutic strategy in cancer treatment [78][79]. Sherif et al. demonstrated that rats receiving tenofovir at a dose of 50 mg/kg for 24 weeks had diminished colorectal cell proliferation attributed to decreased Bcl-2 and cyclin D1 expression [80]. Zidovudine, also known as azidothymidine, is another nucleoside reverse transcriptase inhibitor (NRTI) used in the treatment of human immunodeficiency virus (HIV) [81]. Brown et al. demonstrated Zidovudine’s telomerase inhibition activity in the HT-29 colon cancer cell line [82]. Furthermore, Fang et al. showed that the antitumor activity of zidovudine in colon cancer cells is mediated by increased expression of the p53-Puma/Bax/Noxa pathways favoring apoptosis, and activation of the p53-p21 pathway promoting cell cycle arrest [83]. Efavirenz is a non-nucleoside reverse transcriptase inhibitor (NNRTI) used in the treatment of HIV that is selectively cytotoxic to different tumor cell lines, including colorectal carcinoma, by activating the phosphorylation of p53 [84].
Protease inhibitors (PI) are also drugs that suppress the action of HIV proteases to inhibit viral growth, infectivity, and replication [85]. Indinavir and Saquinavir are PI that suppress the growth of human tumor cells by blocking angiogenesis and matrix metalloproteinases to inhibit tumor invasion and progression. [86]. Furthermore, Mühl et al. reported that Ritonavir synergizes with butyrate to induce apoptosis of CRC cells [87]. The anticancer effect of Ritonavir is most likely due to the inhibition of proteolytic degradation, which causes the accumulation of p21 [88], the decreased production of TNF-α, IL-6, IL-8, and VEGF [89], and the increased expression of anti-inflammatory heme oxygenase-1 [87].
Integrase inhibitors are the latest class of antiretroviral drugs which were approved for HIV therapy due to their efficacy, tolerability, and safety [90]. Raltegravir is an integrase inhibitor that inhibits the Fascin-1-dependent invasion of colorectal tumor cells in vitro and in vivo [91]. Fascin-1 is an actin cross-linking protein whose elevated expression is associated with aggressive clinical progression, dismal prognosis, increased recurrence, and worse survival outcomes in patients with CRC [92][93].

8. Anti-Microbials

Other anti-microbial drugs have been investigated for repurposing in colon cancer treatment including doxycycline, a semi-synthetic antibiotic derivative of tetracycline used in the treatment of a wide variety of infections [94]. Doxycycline has also been shown to inhibit matrix metalloproteinases [95]. Onoda et al. demonstrated that a combination therapy consisting of doxycycline and a COX-2 inhibitor suppressed colon cancer cell proliferation and invasion [96]. Doxycycline reportedly induced apoptosis in a dose-dependent manner through activation of caspases, release of cytochrome C, and translocation of Bax [97].
Another antibiotic with potential in cancer therapeutics is clarithromycin. Clarithromycin is a potent inhibitor of tumor-induced angiogenesis [98] showing increased efficacy when combined with approved anticancer drugs [99][100][101]. It is also implicated in attenuating autophagy in myeloma cells [102]. Targeting autophagy is considered a promising strategy for colon cancer therapy [103][104]. In a study by Petroni et al., clarithromycin was indeed shown to modulate autophagy in human CRC cells and inhibited the growth of tumors by targeting hERG1 [105].
The inhibition of autophagy as a mechanism of anticancer activity is also shared by azithromycin, another macrolide antibiotic [106][107]. Qiao et al. demonstrated that azithromycin had a synergistic antitumor activity with the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in colon cancer cells. Azithromycin may also suppress autophagy by upregulating the expression of p62 and LC-3B to ultimately induce colon cancer cell death [108].
Gemifloxacin is a fluoroquinolone used in the setting of community-acquired pneumonia and acute exacerbations of chronic bronchitis [109]. Kan et al. demonstrated that gemifloxacin inhibits the migration and invasion of SW620 and LoVol colon cancer cells and downregulates Snail to reduce epithelial-to-mesenchymal transition (EMT). Gemifloxacin also suppresses the NF-κB pathway and cytokine-mediated cell migration and invasion as shown by decreased levels of tumor necrosis factor alpha (TNF-alpha), interleukin 6 (IL-6), IL-8, and vascular endothelial growth factor (VEGF) [110].
Antimalarials are also being considered for the treatment of colon cancer. Artesunate is an antimalarial agent recommended for the treatment of patients with severe Plasmodium falciparum malaria [111]. In a preclinical model of CRC, artesunate was found to suppress inflammation and oxidative stress [112]. Efferth et al. demonstrated a cytotoxic action of artesunate on tumor cells via both p53-dependent and -independent pathways [113] implicated in downregulation of β-catenin [114]. Mefloquine, another antimalarial drug, was found to induce growth arrest and apoptosis of CRC cells in mice via inhibition of the tumor NF-κB signaling pathway [115].

References

  1. Giampieri, R.; Cantini, L.; Giglio, E.; Bittoni, A.; Lanese, A.; Crocetti, S.; Pecci, F.; Copparoni, C.; Meletani, T.; Lenci, E.; et al. Impact of Polypharmacy for Chronic Ailments in Colon Cancer Patients: A Review Focused on Drug Repurposing. Cancers 2020, 12, 2724.
  2. Jourdan, J.P.; Bureau, R.; Rochais, C.; Dallemagne, P. Drug repositioning: A brief overview. J. Pharm. Pharmacol. 2020, 72, 1145–1151.
  3. Nowak-Sliwinska, P.; Scapozza, L.; Ruiz i Altaba, A. Drug repurposing in oncology: Compounds, pathways, phenotypes and computational approaches for colorectal cancer. Biochim. Biophys. Acta Rev. Cancer 2019, 1871, 434–454.
  4. Kumar, S.K.; Callander, N.S.; Adekola, K.; Anderson, L.; Baljevic, M.; Campagnaro, E.; Castillo, J.J.; Chandler, J.C.; Costello, C.; Efebera, Y.; et al. Multiple Myeloma, Version 3.2021, NCCN Clinical Practice Guidelines in Oncology. J. Natl. Compr. Cancer Netw. JNCCN 2020, 18, 1685–1717.
  5. Upputuri, B.; Pallapati, M.S.; Tarwater, P. Thalidomide in the treatment of erythema nodosum leprosum (ENL) in an outpatient setting: A five-year retrospective analysis from a leprosy referral centre in India. PLoS Neglected Trop. Dis. 2020, 14, e0008678.
  6. Fink, H.A.; Mac Donald, R.; Rutks, I.R.; Nelson, D.B.; Wilt, T.J. Sildenafil for male erectile dysfunction: A systematic review and meta-analysis. Arch. Intern. Med. 2002, 162, 1349–1360.
  7. Barnett, C.F.; Machado, R.F. Sildenafil in the treatment of pulmonary hypertension. Vasc. Health Risk Manag. 2006, 2, 411–422.
  8. Institute of Medicine (US) Forum on Drug Discovery, Development, and Translation. Transforming Clinical Research in the United States: Challenges and Opportunities: Workshop Summary; National Academies Press (US): Washington, DC, USA, 2010.
  9. Xue, H.; Li, J.; Xie, H.; Wang, Y. Review of Drug Repositioning Approaches and Resources. Int. J. Biol. Sci. 2018, 14, 1232–1244.
  10. U.S. Food and Drug Administration. Step 3: Clinical Research. Available online: https://www.fda.gov/patients/drug-development-process/step-3-clinical-research (accessed on 30 November 2021).
  11. Deotarse, P.J.A.; Baile, M.; Kohle, N.; Kulkarni, A. Drug Repurposing: A Review. Int. J. Pharm. Res. Rev. 2015, 4, 51–58.
  12. Parvathaneni, V.; Kulkarni, N.S.; Muth, A.; Gupta, V. Drug repurposing: A promising tool to accelerate the drug discovery process. Drug Discov. Today 2019, 24, 2076–2085.
  13. Moffat, J.G.; Vincent, F.; Lee, J.A.; Eder, J.; Prunotto, M. Opportunities and challenges in phenotypic drug discovery: An industry perspective. Nat. Rev. Drug Discov. 2017, 16, 531–543.
  14. Packer, M.; Anker, S.D.; Butler, J.; Filippatos, G.; Pocock, S.J.; Carson, P.; Januzzi, J.; Verma, S.; Tsutsui, H.; Brueckmann, M.; et al. Cardiovascular and Renal Outcomes with Empagliflozin in Heart Failure. N. Engl. J. Med. 2020, 383, 1413–1424.
  15. Zannad, F.; Ferreira, J.P.; Pocock, S.J.; Anker, S.D.; Butler, J.; Filippatos, G.; Brueckmann, M.; Ofstad, A.P.; Pfarr, E.; Jamal, W.; et al. SGLT2 inhibitors in patients with heart failure with reduced ejection fraction: A meta-analysis of the EMPEROR-Reduced and DAPA-HF trials. Lancet 2020, 396, 819–829.
  16. Anker, S.D.; Butler, J.; Filippatos, G.; Ferreira, J.P.; Bocchi, E.; Böhm, M.; Brunner-La Rocca, H.P.; Choi, D.J.; Chopra, V.; Chuquiure-Valenzuela, E.; et al. Empagliflozin in Heart Failure with a Preserved Ejection Fraction. N. Engl. J. Med. 2021, 385, 1451–1461.
  17. McMurray, J.J.V.; Solomon, S.D.; Inzucchi, S.E.; Køber, L.; Kosiborod, M.N.; Martinez, F.A.; Ponikowski, P.; Sabatine, M.S.; Anand, I.S.; Bělohlávek, J.; et al. Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction. N. Engl. J. Med. 2019, 381, 1995–2008.
  18. U.S. Food and Drug Administration. FDA Grants Accelerated Approval for Alzheimer’s Drug. Available online: https://www.fda.gov/news-events/press-announcements/fda-grants-accelerated-approval-alzheimers-drug (accessed on 30 November 2021).
  19. Paul, S.M.; Mytelka, D.S.; Dunwiddie, C.T.; Persinger, C.C.; Munos, B.H.; Lindborg, S.R.; Schacht, A.L. How to improve R&D productivity: The pharmaceutical industry’s grand challenge. Nat. Rev. Drug Discov. 2010, 9, 203–214.
  20. Jacquemet, G.; Baghirov, H.; Georgiadou, M.; Sihto, H. L-type calcium channels regulate filopodia stability and cancer cell invasion downstream of integrin signalling. Nat. Commun. 2016, 7, 13297.
  21. Zhang, Z.; Zhou, L.; Xie, N.; Nice, E.C.; Zhang, T.; Cui, Y.; Huang, C. Overcoming cancer therapeutic bottleneck by drug repurposing. Signal Transduct. Target. Ther. 2020, 5, 113.
  22. Lord, S.R.; Cheng, W.C.; Liu, D.; Gaude, E.; Haider, S.; Metcalf, T.; Patel, N.; Teoh, E.J.; Gleeson, F.; Bradley, K.; et al. Integrated Pharmacodynamic Analysis Identifies Two Metabolic Adaption Pathways to Metformin in Breast Cancer. Cell Metab. 2018, 28, 679–688.e674.
  23. Jarada, T.N.; Rokne, J.G.; Alhajj, R. A review of computational drug repositioning: Strategies, approaches, opportunities, challenges, and directions. J. Cheminform. 2020, 12, 46.
  24. Liu, X.; Zhu, F.; Ma, X.H.; Shi, Z.; Yang, S.Y.; Wei, Y.Q.; Chen, Y.Z. Predicting targeted polypharmacology for drug repositioning and multi- target drug discovery. Curr. Med. Chem. 2013, 20, 1646–1661.
  25. Raynal, N.J.; Da Costa, E.M.; Lee, J.T.; Gharibyan, V.; Ahmed, S.; Zhang, H.; Sato, T.; Malouf, G.G.; Issa, J.J. Repositioning FDA-Approved Drugs in Combination with Epigenetic Drugs to Reprogram Colon Cancer Epigenome. Mol. Cancer Ther. 2017, 16, 397–407.
  26. Hradec, J. Pharmacological therapy for chronic heart failure. Vnitr. Lek. 2018, 64, 853–859.
  27. Kubota, M.; Shimizu, M.; Sakai, H.; Yasuda, Y.; Ohno, T.; Kochi, T.; Tsurumi, H.; Tanaka, T.; Moriwaki, H. Renin-angiotensin system inhibitors suppress azoxymethane-induced colonic preneoplastic lesions in C57BL/KsJ-db/db obese mice. Biochem. Biophys. Res. Commun. 2011, 410, 108–113.
  28. Kedika, R.; Patel, M.; Pena Sahdala, H.N.; Mahgoub, A.; Cipher, D.; Siddiqui, A.A. Long-term use of angiotensin converting enzyme inhibitors is associated with decreased incidence of advanced adenomatous colon polyps. J. Clin. Gastroenterol. 2011, 45, e12–e16.
  29. Do Vale, G.T.; Ceron, C.S.; Gonzaga, N.A.; Simplicio, J.A.; Padovan, J.C. Three Generations of β-blockers: History, Class Differences and Clinical Applicability. Curr. Hypertens. Rev. 2019, 15, 22–31.
  30. Nuevo-Tapioles, C.; Santacatterina, F.; Stamatakis, K.; Núñez de Arenas, C.; Gómez de Cedrón, M.; Formentini, L.; Cuezva, J.M. Coordinate β-adrenergic inhibition of mitochondrial activity and angiogenesis arrest tumor growth. Nat. Commun. 2020, 11, 3606.
  31. Engineer, D.R.; Burney, B.O.; Hayes, T.G.; Garcia, J.M. Exposure to ACEI/ARB and β-Blockers Is Associated with Improved Survival and Decreased Tumor Progression and Hospitalizations in Patients with Advanced Colon Cancer. Transl. Oncol. 2013, 6, 539–545.
  32. Bacchi, S.; Palumbo, P.; Sponta, A.; Coppolino, M.F. Clinical pharmacology of non-steroidal anti-inflammatory drugs: A review. Antiinflamm. Antiallergy Agents Med. Chem. 2012, 11, 52–64.
  33. Sheng, J.; Sun, H.; Yu, F.B.; Li, B.; Zhang, Y.; Zhu, Y.T. The Role of Cyclooxygenase-2 in Colorectal Cancer. Int. J. Med. Sci. 2020, 17, 1095–1101.
  34. Dovizio, M.; Tacconelli, S.; Sostres, C.; Ricciotti, E.; Patrignani, P. Mechanistic and pharmacological issues of aspirin as an anticancer agent. Pharmaceuticals 2012, 5, 1346–1371.
  35. Thun, M.J.; Jacobs, E.J.; Patrono, C. The role of aspirin in cancer prevention. Nat. Rev. Clin. Oncol. 2012, 9, 259–267.
  36. Kopp, H.G.; Placke, T.; Salih, H.R. Platelet-derived transforming growth factor-beta down-regulates NKG2D thereby inhibiting natural killer cell antitumor reactivity. Cancer Res. 2009, 69, 7775–7783.
  37. Chan, A.T.; Ogino, S.; Fuchs, C.S. Aspirin and the risk of colorectal cancer in relation to the expression of COX-2. N. Engl. J. Med. 2007, 356, 2131–2142.
  38. McAdam, B.F.; Catella-Lawson, F.; Mardini, I.A.; Kapoor, S.; Lawson, J.A.; FitzGerald, G.A. Systemic biosynthesis of prostacyclin by cyclooxygenase (COX)-2: The human pharmacology of a selective inhibitor of COX-2. Proc. Natl. Acad. Sci. USA 1999, 96, 272–277.
  39. Pal, I.; Dey, K.K.; Chaurasia, M.; Parida, S.; Das, S.; Rajesh, Y.; Sharma, K.; Chowdhury, T.; Mandal, M. Cooperative effect of BI-69A11 and celecoxib enhances radiosensitization by modulating DNA damage repair in colon carcinoma. Tumour Biol. 2016, 37, 6389–6402.
  40. Dulai, P.S.; Singh, S.; Marquez, E.; Khera, R.; Prokop, L.J.; Limburg, P.J.; Gupta, S.; Murad, M.H. Chemoprevention of colorectal cancer in individuals with previous colorectal neoplasia: Systematic review and network meta-analysis. BMJ 2016, 355, i6188.
  41. Xu, X.T.; Hu, W.T.; Zhou, J.Y.; Tu, Y. Celecoxib enhances the radiosensitivity of HCT116 cells in a COX-2 independent manner by up-regulating BCCIP. Am. J. Transl. Res. 2017, 9, 1088–1100.
  42. Bertagnolli, M.M.; Eagle, C.J.; Zauber, A.G.; Redston, M.; Solomon, S.D.; Kim, K.; Tang, J.; Rosenstein, R.B.; Wittes, J.; Corle, D.; et al. Celecoxib for the prevention of sporadic colorectal adenomas. N. Engl. J. Med. 2006, 355, 873–884.
  43. Bansal, A.B.; Cassagnol, M. HMG-CoA Reductase Inhibitors. In StatPearls; StatPearls Publishing: Treasure Island, FL, USA, 2021.
  44. Poynter, J.N.; Gruber, S.B.; Higgins, P.D.; Almog, R.; Bonner, J.D.; Rennert, H.S.; Low, M.; Greenson, J.K.; Rennert, G. Statins and the risk of colorectal cancer. N. Engl. J. Med. 2005, 352, 2184–2192.
  45. Juneja, M.; Kobelt, D.; Walther, W.; Voss, C.; Smith, J.; Specker, E.; Neuenschwander, M.; Gohlke, B.O.; Dahlmann, M.; Radetzki, S.; et al. Statin and rottlerin small-molecule inhibitors restrict colon cancer progression and metastasis via MACC1. PLoS Biol. 2017, 15, e2000784.
  46. Qi, J.H.; Wei, J.N.; Zhang, Z.J.; Dong, L.; Zhang, L.; Mao, Y.Y.; Lei, L.J.; Hu, X.Q.; Bai, W.Q. . Zhonghua Liu Xing Bing Xue Za Zhi 2021, 42, 343–350.
  47. Buse, J.B.; Wexler, D.J.; Tsapas, A.; Rossing, P.; Mingrone, G.; Mathieu, C.; D’Alessio, D.A.; Davies, M.J. 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 2020, 43, 487–493.
  48. Berkovic, M.C.; Mikulic, D.; Bilic-Curcic, I.; Mrzljak, A. How far along are we in revealing the connection between metformin and colorectal cancer? World J. Gastroenterol. 2021, 27, 1362–1368.
  49. Cunha Júnior, A.D.; Bragagnoli, A.C.; Costa, F.O.; Carvalheira, J.B.C. Repurposing metformin for the treatment of gastrointestinal cancer. World J. Gastroenterol. 2021, 27, 1883–1904.
  50. Slattery, M.L.; Herrick, J.S.; Lundgreen, A.; Fitzpatrick, F.A.; Curtin, K.; Wolff, R.K. Genetic variation in a metabolic signaling pathway and colon and rectal cancer risk: mTOR, PTEN, STK11, RPKAA1, PRKAG2, TSC1, TSC2, PI3K and Akt1. Carcinogenesis 2010, 31, 1604–1611.
  51. Pollak, M. Insulin, insulin-like growth factors and neoplasia. Best Pract. Res. Clin. Endocrinol. Metab. 2008, 22, 625–638.
  52. Pollak, M. The insulin and insulin-like growth factor receptor family in neoplasia: An update. Nat. Rev. Cancer 2012, 12, 159–169.
  53. Vial, G.; Detaille, D.; Guigas, B. Role of Mitochondria in the Mechanism(s) of Action of Metformin. Front. Endocrinol. 2019, 10, 294.
  54. Zi, F.; Zi, H.; Li, Y.; He, J.; Shi, Q.; Cai, Z. Metformin and cancer: An existing drug for cancer prevention and therapy. Oncol. Lett. 2018, 15, 683–690.
  55. Nguyen, T.T.; Ung, T.T.; Li, S.; Lian, S.; Xia, Y.; Park, S.Y.; Do Jung, Y. Metformin inhibits lithocholic acid-induced interleukin 8 upregulation in colorectal cancer cells by suppressing ROS production and NF-kB activity. Sci. Rep. 2019, 9, 2003.
  56. Saber, M.M.; Galal, M.A.; Ain-Shoka, A.A.; Shouman, S.A. Combination of metformin and 5-aminosalicylic acid cooperates to decrease proliferation and induce apoptosis in colorectal cancer cell lines. BMC Cancer 2016, 16, 126.
  57. Khader, E.I.; Ismail, W.W.; Mhaidat, N.M.; Alqudah, M.A. Effect of metformin on irinotecan-induced cell cycle arrest in colorectal cancer cell lines HCT116 and SW480. Int. J. Health Sci. 2021, 15, 34–41.
  58. Kim, S.H.; Kim, S.C.; Ku, J.L. Metformin increases chemo-sensitivity via gene downregulation encoding DNA replication proteins in 5-Fu resistant colorectal cancer cells. Oncotarget 2017, 8, 56546–56557.
  59. Rocha, G.Z.; Dias, M.M.; Ropelle, E.R.; Osório-Costa, F.; Rossato, F.A.; Vercesi, A.E.; Saad, M.J.; Carvalheira, J.B. Metformin amplifies chemotherapy-induced AMPK activation and antitumoral growth. Clin. Cancer Res. 2011, 17, 3993–4005.
  60. Ganesan, K.; Rana, M.B.M.; Sultan, S. Oral Hypoglycemic Medications. In StatPearls, 2021 January ed.; StatPearls Publishing: Treasure Island, FL, USA, 2021.
  61. Okada, J.; Yamada, E.; Saito, T.; Yokoo, H.; Osaki, A.; Shimoda, Y.; Ozawa, A.; Nakajima, Y.; Pessin, J.E.; Okada, S.; et al. Dapagliflozin Inhibits Cell Adhesion to Collagen I and IV and Increases Ectodomain Proteolytic Cleavage of DDR1 by Increasing ADAM10 Activity. Molecules 2020, 25, 495.
  62. Kothiwale, S.; Borza, C.M.; Lowe, E.W.; Pozzi, A.; Meiler, J. Discoidin domain receptor 1 (DDR1) kinase as target for structure-based drug discovery. Drug Discov. Today 2015, 20, 255–261.
  63. Saito, T.; Okada, S.; Yamada, E.; Shimoda, Y.; Osaki, A.; Tagaya, Y.; Shibusawa, R.; Okada, J.; Yamada, M. Effect of dapagliflozin on colon cancer cell . Endocr. J. 2015, 62, 1133–1137.
  64. Okada, J.; Matsumoto, S.; Kaira, K.; Saito, T.; Yamada, E.; Yokoo, H.; Katoh, R.; Kusano, M.; Okada, S.; Yamada, M. Sodium Glucose Cotransporter 2 Inhibition Combined With Cetuximab Significantly Reduced Tumor Size and Carcinoembryonic Antigen Level in Colon Cancer Metastatic to Liver. Clin. Colorectal. Cancer 2018, 17, e45–e48.
  65. Lacey, E. Mode of action of benzimidazoles. Parasitol. Today 1990, 6, 112–115.
  66. Nygren, P.; Fryknäs, M.; Agerup, B.; Larsson, R. Repositioning of the anthelmintic drug mebendazole for the treatment for colon cancer. J. Cancer Res. Clin. Oncol. 2013, 139, 2133–2140.
  67. Laudisi, F.; Marônek, M.; Di Grazia, A.; Monteleone, G.; Stolfi, C. Repositioning of Anthelmintic Drugs for the Treatment of Cancers of the Digestive System. Int. J. Mol. Sci. 2020, 21, 4957.
  68. Nygren, P.; Larsson, R. Drug repositioning from bench to bedside: Tumour remission by the antihelmintic drug mebendazole in refractory metastatic colon cancer. Acta Oncol. 2014, 53, 427–428.
  69. Williamson, T.; Bai, R.Y.; Staedtke, V.; Huso, D.; Riggins, G.J. Mebendazole and a non-steroidal anti-inflammatory combine to reduce tumor initiation in a colon cancer preclinical model. Oncotarget 2016, 7, 68571–68584.
  70. Chen, W.; Mook, R.A.; Premont, R.T.; Wang, J. Niclosamide: Beyond an antihelminthic drug. Cell. Signal. 2018, 41, 89–96.
  71. Segditsas, S.; Tomlinson, I. Colorectal cancer and genetic alterations in the Wnt pathway. Oncogene 2006, 25, 7531–7537.
  72. Sack, U.; Walther, W.; Scudiero, D.; Selby, M.; Kobelt, D.; Lemm, M.; Fichtner, I.; Schlag, P.M.; Shoemaker, R.H.; Stein, U. Novel effect of antihelminthic Niclosamide on S100A4-mediated metastatic progression in colon cancer. J. Natl. Cancer Inst. 2011, 103, 1018–1036.
  73. Osada, T.; Chen, M.; Yang, X.Y.; Spasojevic, I.; Vandeusen, J.B.; Hsu, D.; Clary, B.M.; Clay, T.M.; Chen, W.; Morse, M.A.; et al. Antihelminth compound niclosamide downregulates Wnt signaling and elicits antitumor responses in tumors with activating APC mutations. Cancer Res. 2011, 71, 4172–4182.
  74. Wang, J.; Ren, X.R.; Piao, H.; Zhao, S.; Osada, T.; Premont, R.T.; Mook, R.A.; Morse, M.A.; Lyerly, H.K.; Chen, W. Niclosamide-induced Wnt signaling inhibition in colorectal cancer is mediated by autophagy. Biochem. J. 2019, 476, 535–546.
  75. Kang, H.E.; Seo, Y.; Yun, J.S.; Song, S.H.; Han, D.; Cho, E.S.; Cho, S.B.; Jeon, Y.; Lee, H.; Kim, H.S.; et al. Metformin and Niclosamide Synergistically Suppress Wnt and YAP in APC-Mutated Colorectal Cancer. Cancers 2021, 13, 3437.
  76. Wassner, C.; Bradley, N.; Lee, Y. A Review and Clinical Understanding of Tenofovir: Tenofovir Disoproxil Fumarate versus Tenofovir Alafenamide. J. Int. Assoc. Provid. AIDS Care 2020, 19, 2325958220919231.
  77. Hukezalie, K.R.; Thumati, N.R.; Côté, H.C.; Wong, J.M. In vitro and ex vivo inhibition of human telomerase by anti-HIV nucleoside reverse transcriptase inhibitors (NRTIs) but not by non-NRTIs. PLoS ONE 2012, 7, e47505.
  78. Jafri, M.A.; Ansari, S.A.; Alqahtani, M.H.; Shay, J.W. Roles of telomeres and telomerase in cancer, and advances in telomerase-targeted therapies. Genome Med. 2016, 8, 69.
  79. Sanford, S.L.; Welfer, G.A.; Freudenthal, B.D.; Opresko, P.L. Mechanisms of telomerase inhibition by oxidized and therapeutic dNTPs. Nat. Commun. 2020, 11, 5288.
  80. Sherif, D.A.; Makled, M.N.; Suddek, G.M. The HIV reverse transcriptase inhibitor Tenofovir suppressed DMH/HFD-induced colorectal cancer in Wistar rats. Fundam. Clin. Pharmacol. 2021, 35, 940–954.
  81. Kinloch-De Loës, S.; Hirschel, B.J.; Hoen, B.; Cooper, D.A.; Tindall, B.; Carr, A.; Saurat, J.H.; Clumeck, N.; Lazzarin, A.; Mathiesen, L. A controlled trial of zidovudine in primary human immunodeficiency virus infection. N. Engl. J. Med. 1995, 333, 408–413.
  82. Brown, T.; Sigurdson, E.; Rogatko, A.; Broccoli, D. Telomerase inhibition using azidothymidine in the HT-29 colon cancer cell line. Ann. Surg. Oncol. 2003, 10, 910–915.
  83. Fang, X.; Hu, T.; Yin, H.; Yang, J.; Tang, W.; Hu, S.; Xu, X. Differences in telomerase activity and the effects of AZT in aneuploid and euploid cells in colon cancer. Int. J. Oncol. 2017, 51, 525–532.
  84. Hecht, M.; Harrer, T.; Büttner, M.; Schwegler, M.; Erber, S.; Fietkau, R.; Distel, L.V. Cytotoxic effect of efavirenz is selective against cancer cells and associated with the cannabinoid system. AIDS 2013, 27, 2031–2040.
  85. Flexner, C. HIV-protease inhibitors. N. Engl. J. Med. 1998, 338, 1281–1292.
  86. Toschi, E.; Sgadari, C.; Malavasi, L.; Bacigalupo, I.; Chiozzini, C.; Carlei, D.; Compagnoni, D.; Bellino, S.; Bugarini, R.; Falchi, M.; et al. Human immunodeficiency virus protease inhibitors reduce the growth of human tumors via a proteasome-independent block of angiogenesis and matrix metalloproteinases. Int. J. Cancer 2011, 128, 82–93.
  87. Mühl, H.; Paulukat, J.; Höfler, S.; Hellmuth, M.; Franzen, R.; Pfeilschifter, J. 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. Br. J. Pharmacol. 2004, 143, 890–898.
  88. Gaedicke, S.; Firat-Geier, E.; Constantiniu, O.; Lucchiari-Hartz, M.; Freudenberg, M.; Galanos, C.; Niedermann, G. Antitumor effect of the human immunodeficiency virus protease inhibitor ritonavir: Induction of tumor-cell apoptosis associated with perturbation of proteasomal proteolysis. Cancer Res. 2002, 62, 6901–6908.
  89. Pati, S.; Pelser, C.B.; Dufraine, J.; Bryant, J.L.; Reitz, M.S., Jr.; Weichold, F.F. Antitumorigenic effects of HIV protease inhibitor ritonavir: Inhibition of Kaposi sarcoma. Blood 2002, 99, 3771–3779.
  90. Blanco, J.L.; Whitlock, G.; Milinkovic, A.; Moyle, G. HIV integrase inhibitors: A new era in the treatment of HIV. Expert Opin. Pharmacother. 2015, 16, 1313–1324.
  91. Alburquerque-González, B.; Bernabé-García, Á.; Bernabé-García, M.; Ruiz-Sanz, J.; López-Calderón, F.F.; Gonnelli, L.; Banci, L.; Peña-García, J.; Luque, I.; Nicolás, F.J.; et al. The FDA-Approved Antiviral Raltegravir Inhibits Fascin1-Dependent Invasion of Colorectal Tumor Cells In Vitro and In Vivo. Cancers 2021, 13, 861.
  92. Shi, S.; Zheng, H.C.; Zhang, Z.G. Roles of Fascin mRNA expression in colorectal cancer: Meta-analysis and bioinformatics analysis. Mol. Clin. Oncol. 2020, 13, 119–128.
  93. Tampakis, A.; Tampaki, E.C.; Nonni, A.; Kostakis, I.D.; Posabella, A.; Kontzoglou, K.; von Flue, M.; Felekouras, E.; Kouraklis, G.; Nikiteas, N. High fascin-1 expression in colorectal cancer identifies patients at high risk for early disease recurrence and associated mortality. BMC Cancer 2021, 21, 153.
  94. Cunha, B.A.; Sibley, C.M.; Ristuccia, A.M. Doxycycline. Ther. Drug Monit. 1982, 4, 115–135.
  95. Jung, J.J.; Razavian, M.; Kim, H.Y.; Ye, Y.; Golestani, R.; Toczek, J.; Zhang, J.; Sadeghi, M.M. Matrix metalloproteinase inhibitor, doxycycline and progression of calcific aortic valve disease in hyperlipidemic mice. Sci. Rep. 2016, 6, 32659.
  96. Onoda, T.; Ono, T.; Dhar, D.K.; Yamanoi, A.; Fujii, T.; Nagasue, N. Doxycycline inhibits cell proliferation and invasive potential: Combination therapy with cyclooxygenase-2 inhibitor in human colorectal cancer cells. J. Lab. Clin. Med. 2004, 143, 207–216.
  97. Onoda, T.; Ono, T.; Dhar, D.K.; Yamanoi, A.; Nagasue, N. Tetracycline analogues (doxycycline and COL-3) induce caspase-dependent and -independent apoptosis in human colon cancer cells. Int. J. Cancer 2006, 118, 1309–1315.
  98. Yatsunami, J.; Turuta, N.; Wakamatsu, K.; Hara, N.; Hayashi, S. Clarithromycin is a potent inhibitor of tumor-induced angiogenesis. Res. Exp. Med. 1997, 197, 189–197.
  99. Carella, A.M.; Beltrami, G.; Pica, G.; Carella, A.; Catania, G. Clarithromycin potentiates tyrosine kinase inhibitor treatment in patients with resistant chronic myeloid leukemia. Leuk. Lymphoma 2012, 53, 1409–1411.
  100. Schafranek, L.; Leclercq, T.M.; White, D.L.; Hughes, T.P. Clarithromycin enhances dasatinib-induced cell death in chronic myeloid leukemia cells, by inhibition of late stage autophagy. Leuk. Lymphoma 2013, 54, 198–201.
  101. Komatsu, S.; Moriya, S.; Che, X.F.; Yokoyama, T.; Kohno, N.; Miyazawa, K. 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. Biochem. Biophys. Res. Commun. 2013, 437, 41–47.
  102. Nakamura, M.; Kikukawa, Y.; Takeya, M.; Mitsuya, H.; Hata, H. Clarithromycin attenuates autophagy in myeloma cells. Int. J. Oncol. 2010, 37, 815–820.
  103. Mokarram, P.; Albokashy, M.; Zarghooni, M.; Moosavi, M.A.; Sepehri, Z.; Chen, Q.M.; Hudecki, A.; Sargazi, A.; Alizadeh, J.; Moghadam, A.R.; et al. New frontiers in the treatment of colorectal cancer: Autophagy and the unfolded protein response as promising targets. Autophagy 2017, 13, 781–819.
  104. Burada, F.; Nicoli, E.R.; Ciurea, M.E.; Uscatu, D.C.; Ioana, M.; Gheonea, D.I. Autophagy in colorectal cancer: An important switch from physiology to pathology. World J. Gastrointest. Oncol. 2015, 7, 271–284.
  105. Petroni, G.; Bagni, G.; Iorio, J.; Duranti, C.; Lottini, T.; Stefanini, M.; Kragol, G.; Becchetti, A.; Arcangeli, A. Clarithromycin inhibits autophagy in colorectal cancer by regulating the hERG1 potassium channel interaction with PI3K. Cell Death Dis. 2020, 11, 161.
  106. Tanaka, H.; Hino, H.; Moriya, S.; Kazama, H.; Miyazaki, M.; Takano, N.; Hiramoto, M.; Tsukahara, K.; Miyazawa, K. 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. Biochem. Biophys. Rep. 2020, 22, 100750.
  107. Toriyama, K.; Takano, N.; Kokuba, H.; Kazama, H.; Moriya, S.; Hiramoto, M.; Abe, S.; Miyazawa, K. Azithromycin enhances the cytotoxicity of DNA-damaging drugs via lysosomal membrane permeabilization in lung cancer cells. Cancer Sci. 2021, 112, 3324–3337.
  108. Qiao, X.; Wang, X.; Shang, Y.; Li, Y.; Chen, S.Z. 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 Commun. 2018, 38, 43.
  109. Zhanel, G.G.; Fontaine, S.; Adam, H.; Schurek, K.; Mayer, M.; Noreddin, A.M.; Gin, A.S.; Rubinstein, E.; Hoban, D.J. A Review of New Fluoroquinolones: Focus on their Use in Respiratory Tract Infections. Treat. Respir. Med. 2006, 5, 437–465.
  110. Kan, J.Y.; Hsu, Y.L.; Chen, Y.H.; Chen, T.C.; Wang, J.Y.; Kuo, P.L. Gemifloxacin, a fluoroquinolone antimicrobial drug, inhibits migration and invasion of human colon cancer cells. Biomed Res. Int. 2013, 2013, 159786.
  111. Barradell, L.B.; Fitton, A. Artesunate. A review of its pharmacology and therapeutic efficacy in the treatment of malaria. Drugs 1995, 50, 714–741.
  112. Kumar, V.L.; Verma, S.; Das, P. Artesunate suppresses inflammation and oxidative stress in a rat model of colorectal cancer. Drug Dev. Res. 2019, 80, 1089–1097.
  113. Efferth, T.; Sauerbrey, A.; Olbrich, A.; Gebhart, E.; Rauch, P.; Weber, H.O.; Hengstler, J.G.; Halatsch, M.E.; Volm, M.; Tew, K.D.; et al. Molecular modes of action of artesunate in tumor cell lines. Mol. Pharmacol. 2003, 64, 382–394.
  114. Verma, S.; Das, P.; Kumar, V.L. 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. Chem. Biol. Interact. 2017, 278, 84–91.
  115. Xu, X.; Wang, J.; Han, K.; Li, S.; Xu, F.; Yang, Y. Antimalarial drug mefloquine inhibits nuclear factor kappa B signaling and induces apoptosis in colorectal cancer cells. Cancer Sci. 2018, 109, 1220–1229.
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Subjects: Oncology
Contributors MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to https://encyclopedia.pub/register :
Talal El Zarif
,
Hisham Bahmad
,
,
Diana De Oliveira Gomes
,
Marc Machaalani
,
Rashad Nawfal
,
Gianfranco Bittar
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Entry Collection: Gastrointestinal Disease
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Update Date: 18 May 2022
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