Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, Jemal A. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024;74(3):229–63.

PubMed  Google Scholar 

Singh N, Vayer P, Tanwar S, Poyet JL, Tsaioun K, Villoutreix BO. Drug discovery and development: introduction to the general public and patient groups. Front Drug Discov. 2023;3:1201419.

Google Scholar 

Ávalos-Moreno M, López-Tejada A, Blaya-Cánovas JL, Cara-Lupiañez FE, González-González A, Lorente JA, Sánchez-Rovira P, Granados-Principal S. Drug repurposing for triple-negative breast cancer. J Pers Med. 2020;10(4): 200.

PubMed  PubMed Central  Google Scholar 

Fogel DB. Factors associated with clinical trials that fail and opportunities for improving the likelihood of success: a review. Contemp Clin Trials Commun. 2018;11:156–64.

PubMed  PubMed Central  Google Scholar 

Swinney DC, Anthony J. How were new medicines discovered? Nat Rev Drug Discov. 2011;10(7):507–19.

PubMed  Google Scholar 

Hilas O. Trends in FDA-approved cancer therapies. US Pharm Pharm Resour Clin Excell. 2023;48(10):14.

Google Scholar 

Sleire L, Førde HE, Netland IA, Leiss L, Skeie BS, Enger PØ. Drug repurposing in cancer. Pharmacol Res. 2017;124:74–91.

PubMed  Google Scholar 

Sonaye HV, Sheikh RY, Doifode CA. Drug repurposing: iron in the fire for older drugs. Biomed Pharmacother. 2021;141: 111638.

PubMed  Google Scholar 

Pushpakom S, Iorio F, Eyers PA, Escott KJ, Hopper S, Wells A, Doig A, Guilliams T, Latimer J, McNamee C, Norris A, Sanseau P, Cavalla D, Pirmohamed M. Drug repurposing: progress, challenges and recommendations. Nat Rev Drug Discov. 2019;18(1):41–58.

PubMed  Google Scholar 

Fu L, Jin W, Zhang J, Zhu L, Lu J, Zhen Y, Zhang L, Ouyang L, Liu B, Yu H. Repurposing non-oncology small-molecule drugs to improve cancer therapy: current situation and future directions. Acta Pharm Sin B. 2022;12(2):532–57.

PubMed  Google Scholar 

Hughes JP, Rees S, Kalindjian SB, Philpott KL. Principles of early drug discovery. Br J Pharmacol. 2011;162(6):1239–49.

PubMed  PubMed Central  Google Scholar 

Powers M, Greven M, Kleinman R, Nguyen QD, Do D. Recent advances in the management and understanding of diabetic retinopathy. F1000Res. 2017;6: 2063.

PubMed  PubMed Central  Google Scholar 

Roessler HI, Knoers NVAM, van Haelst MM, van Haaften G. Drug repurposing for rare diseases. Trends Pharmacol Sci. 2021;42(4):255–67.

PubMed  Google Scholar 

Allarakhia M. Open-source approaches for the repurposing of existing or failed candidate drugs: learning from and applying the lessons across diseases. Drug Des Dev Ther. 2013;7:753–66.

Google Scholar 

Rudrapal M, Khairnar SJ, Jadhav AG. Drug repurposing (DR): an emerging approach in drug discovery. In: Drug repurposing—hypothesis, molecular aspects and therapeutic applications. London: IntechOpen Limited; 2020.

Rao N, Poojari T, Poojary C, Sande R, Sawant S. Drug repurposing: a shortcut to new biological entities. Pharm Chem J. 2022;56(9):1203–14.

PubMed  PubMed Central  Google Scholar 

Hodos RA, Kidd BA, Shameer K, Readhead BP, Dudley JT. In silico methods for drug repurposing and pharmacology. Wiley Interdiscip Rev Syst Biol Med. 2016;8(3):186–210.

PubMed  PubMed Central  Google Scholar 

Zhang Z, Zhou L, Xie N, Nice EC, Zhang T, Cui Y, Huang C. Overcoming cancer therapeutic bottleneck by drug repurposing. Signal Transduct Target Ther. 2020;5(1):113.

PubMed  PubMed Central  Google Scholar 

Li L, Hu M, Wang T, Chen H, Xu L. Repositioning aspirin to treat lung and breast cancers and overcome acquired resistance to targeted therapy. Front Oncol. 2020;9:1503.

PubMed  PubMed Central  Google Scholar 

Chan AT, Ogino S, Fuchs CS. Aspirin use and survival after diagnosis of colorectal cancer. JAMA. 2009;302(6):649–58.

PubMed  PubMed Central  Google Scholar 

Howell JJ, Hellberg K, Turner M, Talbott G, Kolar MJ, Ross DS, Hoxhaj G, Saghatelian A, Shaw RJ, Manning BD. Metformin inhibits hepatic mTORC1 signaling via dose-dependent mechanisms involving AMPK and the TSC complex. Cell Metab. 2017;25(2):463–71.

PubMed  PubMed Central  Google Scholar 

Kalender A, Selvaraj A, Kim SY, Gulati P, Brûlé S, Viollet B, Kemp BE, Bardeesy N, Dennis P, Schlager JJ, Marette A, Kozma SC, Thomas G. Metformin, independent of AMPK, inhibits mTORC1 in a rag GTPase-dependent manner. Cell Metab. 2010;11(5):390–401.

PubMed  PubMed Central  Google Scholar 

Zheng Z, Bian Y, Zhang Y, Ren G, Li G. Metformin activates AMPK/SIRT1/NF-κB pathway and induces mitochondrial dysfunction to drive caspase3/GSDME-mediated cancer cell pyroptosis. Cell Cycle. 2020;19(10):1089–104.

PubMed  PubMed Central  Google Scholar 

Yang J, Zhou Y, Xie S, Wang J, Li Z, Chen L, Mao M, Chen C, Huang A, Chen Y, Zhang X, Khan NUH, Wang L, Zhou J. Metformin induces ferroptosis by inhibiting UFMylation of SLC7A11 in breast cancer. J Exp Clin Cancer Res. 2021;40(1): 206.

PubMed  PubMed Central  Google Scholar 

Verma S, Chitikela S, Singh V, et al. A phase II study of metformin plus pemetrexed and carboplatin in patients with non-squamous non-small cell lung cancer (METALUNG). Med Oncol. 2023;40(7):192. https://doi.org/10.1007/s12032-023-02057-y.

PubMed  Google Scholar 

Udumula MP, Poisson LM, Dutta I, et al. Divergent metabolic effects of metformin merge to enhance eicosapentaenoic acid metabolism and inhibit ovarian cancer in vivo. Cancers (Basel). 2022;14(6):1504. https://doi.org/10.3390/cancers14061504.

PubMed  PubMed Central  Google Scholar 

Litchfield LM, Mukherjee A, Eckert MA, et al. Hyperglycemia-induced metabolic compensation inhibits metformin sensitivity in ovarian cancer. Oncotarget. 2015;6(27):23548–60. https://doi.org/10.18632/oncotarget.4556.

PubMed  PubMed Central  Google Scholar 

Parikh AB, Kozuch P, Rohs N, Becker DJ, Levy BP. Metformin as a repurposed therapy in advanced non-small cell lung cancer (NSCLC): results of a phase II trial. Investig N Drugs. 2017;35(6):813–9. https://doi.org/10.1007/s10637-017-0511-7.

Google Scholar 

D’Amato RJ, Loughnan MS, Flynn E, Folkman J. Thalidomide is an inhibitor of angiogenesis. Proc Natl Acad Sci U S A. 1994;91(9):4082–5. https://doi.org/10.1073/pnas.91.9.4082.

PubMed  PubMed Central  Google Scholar 

Fine HA, Wen PY, Maher EA, et al. Phase II trial of thalidomide and carmustine for patients with recurrent high-grade gliomas. J Clin Oncol. 2003;21(12):2299–304. https://doi.org/10.1200/JCO.2003.08.045.

PubMed  Google Scholar 

Barlogie B, Tricot G, Anaissie E, et al. Thalidomide and hematopoietic-cell transplantation for multiple myeloma. N Engl J Med. 2006;354(10):1021–30. https://doi.org/10.1056/NEJMoa053583.

PubMed  Google Scholar 

Işeri OD, Sahin FI, Terzi YK, Yurtcu E, Erdem SR, Sarialioglu F. Beta-adrenoreceptor antagonists reduce cancer cell proliferation, invasion, and migration. Pharm Biol. 2014;52(11):1374–81.

PubMed  Google Scholar 

Brohée L, Peulen O, Nusgens B, Castronovo V, Thiry M, Colige AC, Deroanne CF. Propranolol sensitizes prostate cancer cells to glucose metabolism inhibition and prevents cancer progression. Sci Rep. 2018;8(1):7050.

PubMed  PubMed Central  Google Scholar 

Ramondetta LM, Hu W, Thaker PH, Urbauer DL, Chisholm GB, Westin SN, Sun Y, Ramirez PT, Fleming N, Sahai SK, Nick AM, Arevalo JMG, Dizon T, Coleman RL, Cole SW, Sood AK. Prospective pilot trial with combination of propranolol with chemotherapy in patients with epithelial ovarian cancer and evaluation on circulating immune cell gene expression. Gynecol Oncol. 2019;154(3):524–30.

PubMed  PubMed Central  Google Scholar 

Chang PY, Huang WY, Lin CL, Huang TC, Wu YY, Chen JH, Kao CH. Propranolol reduces cancer risk: a population-based cohort study. Medicine (Baltim). 2015;94(27): e1097.

Google Scholar 

Pasquier E, Ciccolini J, Carre M, et al. Propranolol potentiates the anti-angiogenic effects and anti-tumor efficacy of chemotherapy agents: implication in breast cancer treatment. Oncotarget. 2011;2(10):797–809. https://doi.org/10.18632/oncotarget.343.

PubMed  PubMed Central  Google Scholar 

Palm D, Lang K, Niggemann B, et al. The norepinephrine-driven metastasis development of PC-3 human prostate cancer cells in BALB/c nude mice is inhibited by beta-blockers. Int J Cancer. 2006;118(11):2744–9. https://doi.org/10.1002/ijc.21723.

PubMed  Google Scholar 

Xu T, Xiao X, Zheng S, et al. Antiangiogenic effect of propranolol on the growth of the neuroblastoma xenografts in nude mice. J Pediatr Surg. 2013;48(12):2460–5. https://doi.org/10.1016/j.jpedsurg.2013.08.022.

PubMed  Google Scholar 

Huang KM, Liang S, Yeung S, Oiyemhonlan E, Cleveland KH, Parsa C, Orlando R, Meyskens FL Jr., Andresen BT, Huang Y. Topically applied carvedilol attenuates solar ultraviolet radiation induced skin carcinogenesis. Cancer Prev Res (Phila). 2017;10(10):598–606.

PubMed  Google Scholar 

Kim ST, Park KH, Oh SC, Seo JH, Kim JS, Shin SW, Kim YH. How does inhibition of the renin–angiotensin system affect the prognosis of advanced gastric cancer patients receiving platinum-based chemotherapy? Oncology. 2012;83(6):354–60.

PubMed  Google Scholar 

Alizadeh J, Zeki AA, Mirzaei N, Tewary S, Rezaei Moghadam A, Glogowska A, Nagakannan P, Eftekharpour E, Wiechec E, Gordon JW, Xu FY, Field JT, Yoneda KY, Kenyon NJ, Hashemi M, Hatch GM, Hombach-Klonisch S, Klonisch T, Ghavami S. Mevalonate cascade inhibition by simvastatin induces the intrinsic apoptosis pathway via depletion of isoprenoids in tumor cells. Sci Rep. 2017;7:44841.