327
Views
29
CrossRef citations to date
0
Altmetric
Patenting perspective

Drug repurposing for anticancer therapies. A lesson from proton pump inhibitors

&
Pages 15-25 | Received 24 Oct 2019, Accepted 11 Dec 2019, Published online: 25 Dec 2019

References

  • Global Burden of Disease Cancer Collaboration,Fitzmaurice C, Abate D, Abbasi N, et al. Global, regional, and national cancer incidence, mortality, years of life lost, years lived with disability, and disability-adjusted life-years for 29 cancer groups, 1990 to 2017: a systematic analysis for the global burden of disease study. JAMA Oncol 2019 Sep 27. Epub ahead of print. doi:10.1001/jamaoncol.2019.2996.
  • Sun J, Wei Q, Zhou Y, et al. A systematic analysis of FDA-approved anticancer drugs. BMC Syst Biol. 2017;11(Suppl 5):87.
  • Prasad V, De Jesús K, Mailankody S. The high price of anticancer drugs: origins, implications, barriers, solutions. Nat Rev Clin Oncol. 2017;14(6):381–390.
  • Bosco-Lévy P, de Boissieu P, Gouverneur A, et al. National trends in use and costs of oral anticancer drugs in France: an 8-year population-based study. Pharmacoepidemiol Drug Saf. 2017;26:1233–1241.
  • Mariotto AB, Yabroff KR, Shao Y, et al. Projections of the cost of cancer care in the United States: 2010–2020. J Natl Cancer Inst. 2011;103:117–128.
  • Yabroff KR, Borowski L, Lipscomb J. Economic studies in colorectal cancer: challenges in measuring and comparing costs. J Natl Cancer Inst Monogr. 2013;2013:62–78.
  • Wissinger E, Griebsch I, Lungershausen J, et al. The economic burden of head and neck cancer: a systematic literature review. Pharmacoeconomics. 2014;32:865–882.
  • Trogdon JG, Tangka FKL, Ekwueme DU, et al. State-Level projections of cancer-related medical care costs: 2010 to 2020. Am J Manag Care. 2012;18:525–532.
  • Bach PB. Limits on Medicare’s ability to control rising spending on cancer drugs. N Engl J Med. 2009;360:626–633.
  • Schrag D. The price tag on progress—chemotherapy for colorectal cancer. N Engl J Med. 2004;351:317–319.
  • Bates D, Eastman A. Microtubule destabilizing agents: far more than just antimitotic anticancer drugs. Br J Clin Pharmacol. 2017;83:255–268.
  • Lajous H, Lelièvre B, Vauléon E, et al. Rethinking Alkylating(-Like) agents for solid tumor management. Trends Pharmacol Sci. 2019;40:342–357.
  • Lu S, Li Z. Rethinking our approach of combining novel agents with standard chemotherapy in small cell lung cancer. J Thorac Oncol. 2019;14:580–582.
  • Ikemura K, Hiramatsu S, Okuda M. Drug repositioning of proton pump inhibitors for enhanced efficacy and safety of cancer chemotherapy. Front Pharmacol. 2017;8:911.
  • Lu ZN, Tian B, Guo XL. Repositioning of proton pump inhibitors in cancer therapy. Cancer Chemother Pharmacol. 2017;80:925–937.
  • Gillies RJ, Pilot C, Marunaka Y, et al. Targeting acidity in cancer and diabetes. Biochim Biophys Acta Rev Cancer. 2019;1871:273–280.
  • Iessi E, Logozzi M, Mizzoni D, et al. Rethinking the Combination of Proton Exchanger Inhibitors in Therapy C. Metabolites 2017;8(1):2.
  • Spugnini E, Fais S. Proton pump inhibition and cancer therapeutics: A specific tumor targeting or it is a phenomenon secondary to a systemic buffering? Semin Cancer Biol. 2017;43:111–118.
  • T T A, Thor KB. Drug repositioning: identifying and developing new uses for existing drugs. Nat Rev Drug Discov. 2004;3:673–683.
  • Shim JS, Liu JO. Recent advances in drug repositioning for the discovery of new anticancer drugs. Int J Biol Sci. 2014;10:654− 663.
  • Farley A, Wruble LD, Humphries TJ. Rabeprazole versus ranitidine for the treatment of erosive gastroesophageal reflux disease: a double-blind, randomized clinical trial: rabeprazole study group. Am J Gastroenterol. 2000;95:1894–1899.
  • Huang JQ, Hunt RH. pH, healing rate and symptom relief in acid-related diseases. Yale J Biol Med. 1996;69:159–174.
  • Strand DS, Kim D, Peura DA. 25 Years of Proton Pump Inhibitors: A Comprehensive Review. Gut Liver. 2017;11:27–37.
  • Sachs G, Shin JM, Howden CW. Review article: the clinical pharmacology of proton pump inhibitors. Aliment Pharmacol Ther. 2006;23(Suppl 2):2–8.
  • Smelick GS, Heffron TP, Chu L, et al. Prevalence of acid-reducing agents (ARA) in cancer populations and ARA drug-drug interaction potential for molecular targeted agents in clinical development. Mol Pharm. 2013;10:4055–4062.
  • Fang YH, Yang YH, Hsieh MJ, et al. Concurrent proton-pump inhibitors increase risk of death for lung cancer patients receiving 1st-line gefitinib treatment - a nationwide population-based study. Cancer Manag Res. 2019;11:8539–8546.
  • Suzuki K, Doki K, Homma M, et al. Co-administration of proton pump inhibitors delays elimination of plasma methotrexate in high-dose methotrexate therapy. Br J Clin Pharmacol. 2009;67:44–49.
  • Ikemura K, Hamada Y, Kaya C, et al. Lansoprazole exacerbates pemetrexed-mediated hematologic toxicity by competitive inhibition of renal basolateral human organic anion transporter 3. Drug Metab Dispos. 2016;44:1543–1549.
  • Narumi K, Sato Y, Kobayashi M, et al. Effects of proton pump inhibitors and famotidine on elimination of plasma methotrexate: evaluation of drug-drug interactions mediated by organic anion transporter 3. Biopharm Drug Dispos. 2017;38:501–508.
  • Kurata T, Iwamoto T, Kawahara Y, et al. Characteristics of pemetrexed transport by renal basolateral organic anion transporter hOAT3. Drug Metab Pharmacokinet. 2014;29:148–153.
  • Fais S, Venturi G, Gatenby B. Microenvironmental acidosis in carcinogenesis and metastases: new strategies in prevention and therapy. Cancer Metastasis Rev. 2014;33:1095–1108.
  • Taylor S, Spugnini EP, Assaraf YG, et al. Microenvironment acidity as a major determinant of tumor chemoresistance: proton pump inhibitors (PPIs) as a novel therapeutic approach. Drug Resist Updat. 2015;23:69–78.
  • Fais S. Evidence-based support for the use of proton pump inhibitors in cancer therapy. J Transl Med. 2015;13:368.
  • Spugnini EP, Sonveaux P, Stock C, et al. Proton channels and exchangers in cancer. Biochim Biophys Acta. 2015;1848:2715–2726.
  • Pillai SR, Damaghi M, Marunaka Y, et al. Causes, consequences, and therapy of tumors acidosis. Cancer Metastasis Rev. 2019;38:205–222.
  • Luciani F, Spada M, De Milito A, et al. Effect of proton pump inhibitor pretreatment on resistance of solid tumors to cytotoxic drugs. J Natl Cancer Inst. 2004;96:1702–1713.
  • De Milito A, Iessi E, Logozzi M, et al. Proton pump inhibitors induce apoptosis of human B-cell tumors through a caspase-independent mechanism involving reactive oxygen species. Cancer Res. 2007;67:5408–5417.
  • De Milito A, Canese R, Marino ML, et al. pH-dependent antitumor activity of proton pump inhibitors against human melanoma is mediated by inhibition of tumor acidity. Int J Cancer. 2010;127:207–219.
  • Azzarito T, Venturi G, Cesolini A, et al. Lansoprazole induces sensitivity to suboptimal doses of paclitaxel in human melanoma. Cancer Lett. 2015;356:697–703.
  • Canitano A, Iessi E, Spugnini EP, et al. Proton pump inhibitors induce a caspase-independent antitumor effect against human multiple myeloma. Cancer Lett. 2016;376:278–283.
  • Zhang S, Wang Y, Li SJ. Lansoprazole induces apoptosis of breast cancer cells through inhibition of intracellular proton extrusion. Biochem Biophys Res Commun. 2014;448:424–429.
  • Chen M, Huang SL, Zhang XQ, et al. Reversal effects of pantoprazole on multidrug resistance in human gastric adenocarcinoma cells by down-regulating the V-ATPases/mTOR/HIF-1α/P-gp and MRP1 signaling pathway in vitro and in vivo. J Cell Biochem. 2012;113:2474–2487.
  • Fan S, Niu Y, Tan N, et al. LASS2 enhances chemosensitivity of breast cancer by counteracting acidic tumor microenvironment through inhibiting activity of V-ATPase proton pump. Oncogene. 2013;32:1682–1690.
  • Patel KJ, Lee C, Tan Q, et al. Use of the proton pump inhibitor pantoprazole to modify the distribution and activity of doxorubicin: a potential strategy to improve the therapy of solid tumors. Clin Cancer Res. 2013;19:6766–6776.
  • Schempp CM, von Schwarzenberg K, Schreiner L, et al. V-ATPase inhibition regulates anoikis resistance and metastasis of cancer cells. Mol Cancer Ther. 2014;13:926–937.
  • Tan Q, Joshua AM, Saggar JK, et al. Effect of pantoprazole to enhance activity of docetaxel against human tumour xenografts by inhibiting autophagy. Br J Cancer. 2015;112:832–840.
  • Schneider LS, von Schwarzenberg K, Lehr T, et al. Vacuolar-ATPase inhibition blocks iron metabolism to mediate therapeutic effects in breast cancer. Cancer Res. 2015;75:2863–2874.
  • Yu M, Lee C, Wang M, et al. Influence of the proton pump inhibitor lansoprazole on distribution and activity of doxorubicin in solid tumors. Cancer Sci. 2015;106:1438–1447.
  • Lee YY, Jeon HK, Hong JE, et al. Proton pump inhibitors enhance the effects of cytotoxic agents in chemoresistant epithelial ovarian carcinoma. Oncotarget. 2015;6:35040–35050.
  • Avnet S, Lemma S, Cortini M, et al. Altered pH gradient at the plasma membrane of osteosarcoma cells is a key mechanism of drug resistance. Oncotarget. 2016;7:63408–63423.
  • Lu ZN, Shi ZY, Dang YF, et al. Pantoprazole pretreatment elevates sensitivity to vincristine in drug-resistant oral epidermoid carcinoma in vitro and in vivo. Biomed Pharmacother. 2019;120:109478.
  • Spugnini EP, Buglioni S, Carocci F, et al. High dose lansoprazole combined with metronomic chemotherapy: a phase I/II study in companion animals with spontaneously occurring tumors. Transl Med J 2014;12:225.
  • Spugnini EP, Baldi A, Buglioni S, et al. Lansoprazole as a rescue agent in chemoresistant tumors: a phase I/II study in companion animals with spontaneously occurring tumors. Transl Med J 2011;9:221.
  • Walsh M, Fais S, Spugnini EP, et al. Proton pump inhibitors for the treatment of cancer in companion animals. J Exp Clin Cancer Res. 2015;34:93.
  • Ferrari S, Perut F, Fagioli F, et al. Proton pump inhibitor chemosensitization in human osteosarcoma: from the bench to the patients’ bed. J Transl Med. 2013;11:268.
  • Brana I, Ocana A, Chen EX, et al. A phase I trial of pantoprazole in combination with doxorubicin in patients with advanced solid tumors: evaluation of pharmacokinetics of both drugs and tissue penetration of doxorubicin. Invest New Drugs. 2014;32:1269–1277.
  • Wang BY, Zhang J, Wang JL, et al. Intermittent high dose proton pump inhibitor enhances the antitumor effects of chemotherapy in metastatic breast cancer. J Exp Clin Cancer Res. 2015;34:85.
  • Falcone R, Roberto M, D’Antonio C, et al. High-doses of proton pump inhibitors in refractory gastro-intestinal cancer: A case series and the state of art. Dig Liver Dis. 2016;48:1503–1505.
  • Marchetti P, Milano A, D’Antonio C, et al. Association between proton pump inhibitors and metronomic capecitabine as salvage treatment for patients with advanced gastrointestinal tumors: a randomized phase II trial. Clin Colorectal Cancer. 2016;15:377–380.
  • Papagerakis S, Bellile E, Peterson LA, et al. Proton pump inhibitors and histamine 2 blockers are associated with improved overall survival in patients with head and neck squamous carcinoma. Cancer Prev Res (Phila). 2014;7:1258–1269.
  • Li J, Trone D, Mendell J, et al. A drug-drug interaction study to assess the potential effect of acid-reducing agent, lansoprazole, on quizartinib pharmacokinetics. Cancer Chemother Pharmacol. 2019;84:799–807.
  • Mir O, Touati N, Lia M, et al. Impact of concomitant administration of gastric acid-suppressive agents and pazopanib on outcomes in soft-tissue sarcoma patients treated within the EORTC 62043/62072 Trials. Clin Cancer Res. 2019;25:1479–1485.
  • Abbas MK, Zaidi ARZ, Robert CA, et al. The safety of long-term daily usage of a proton pump inhibitor: a literature review. Cureus. 2019;11:e5563.
  • Brusselaers N, Lagergren J, Engstrand L. Duration of use of proton pump inhibitors and the risk of gastric and oesophageal cancer. Cancer Epidemiol. 2019;62:101585.
  • Laoveeravat P, Thavaraputta S, Vutthikraivit W, et al. Proton pump inhibitors and histamine-2 receptor antagonists on the risk of pancreatic cancer: a systematic review and meta-analysis. QJM. 2019 Sep 10:hcz234. Epub ahead of print] PubMed PMID: 31503318. DOI: 10.1093/qjmed/hcz234.
  • Nielsen HV. Proton pump inhibitor prescriptions and breast cancer recurrence: A Danish nationwide prospective cohort study research year report. Denmark: Aarhus University; 2018.
  • Ding DC, Sung FC, Chen W, et al. Proton pump inhibitors reduce breast cancer risk in gastric ulcer patients: A population-based cohort study. Breast J. Epub ahead of print] PubMed PMID: 31478297 Sep 2 2019. DOI:10.1111/tbj.13519.
  • Chen CH, Lee CZ, Lin YC, et al. Negative association of proton pump inhibitors with subsequent development of breast cancer: a nationwide population-based study. J Clin Pharmacol. 2019;59:350–355.
  • Launay-Vacher V, Izzedine H, Karie S, et al. Renal tubular drug transporters. Nephron Physiol. 2006;103:p97–p106.
  • Inui KI, Masuda S, Saito H. Cellular and molecular aspects of drug transport in the kidney. Kidney Int. 2000;58:944–958.
  • Liu HC, Jamshidi N, Chen Y, et al. An Organic Anion Transporter 1 (OAT1)-centered metabolic network. J Biol Chem. 2016;291:19474–19486.
  • Dasari S, Tchounwou PB. Cisplatin in cancer therapy: molecular mechanisms of action. Eur J Pharmacol. 2014;740:364–378.
  • Singh R, Fazal Z, Freemantle SJ, et al. Mechanisms of cisplatin sensitivity and resistance in testicular germ cell tumors. Cancer Drug Resist. 2019;2:580–594.
  • Ma Y, Zhang NP, An N, et al. Clinical efficacy of weekly cisplatin for treatment of patients with breast cancer. Medicine (Baltimore). 2019;98:e17114.
  • Arbour KC, Riely GJ. Systemic therapy for locally advanced and metastatic non-small cell lung cancer: a review. JAMA. 2019;322:764–774.
  • Wilmes A, Bielow C, Ranninger C, et al. Mechanism of cisplatin proximal tubule toxicity revealed by integrating transcriptomics, proteomics, metabolomics and biokinetics. Toxicol In Vitro. 2015;30:117–127.
  • Yang Y, Chang J, Huang C, et al. A randomised, multicentre open-label phase II study to evaluate the efficacy, tolerability and pharmacokinetics of oral vinorelbine plus cisplatin versus intravenous vinorelbine plus cisplatin in Chinese patients with chemotherapy-naive unresectable or metastatic non-small cell lung cancer. J Thorac Dis. 2019;11:3347–3359.
  • Pearson SE, Taylor J, Patel P, et al. Cancer survivors treated with platinum-based chemotherapy affected by ototoxicity and the impact on quality of life: a narrative synthesis systematic review. Int J Audiol. 2019;58:685–695.
  • Pabla N, Dong Z. Cisplatin nephrotoxicity: mechanisms and renoprotective strategies. Kidney Int. 2008;73:994–1007.
  • Ojha S, Venkataraman B, Kurdi A, et al. Plant-Derived agents for counteracting cisplatin-induced nephrotoxicity. Oxid Med Cell Longev. 2016;2016:4320374.
  • Ikemura K, Oshima K, Enokiya T, et al. Co-administration of proton pump inhibitors ameliorates nephrotoxicity in patients receiving chemotherapy with cisplatin and fluorouracil: a retrospective cohort study. Cancer Chemother Pharmacol. 2017;79:943–949.
  • Campillos M, Kuhn M, Gavin AC, et al. Drug target identification using side-effect similarity. Science. 2008 Jul 11; 321(5886):263–266.
  • Zheng M, Luan S, Gao S, et al. Proton pump inhibitor ilaprazole suppresses cancer growth by targeting T-cell-originated protein kinase. Oncotarget. 2017;8:39143–39153.
  • Vishvakarma NK, Singh SM. Immunopotentiating effect of proton pump inhibitor pantoprazole in a lymphoma-bearing murine host: implication in antitumor activation of tumor-associated macrophages. Immunol Lett. 2010;13:83–92.
  • Vishvakarma NK, Singh SM. Augmentation of myelopoiesis in a murine host bearing a T cell lymphoma following in vivo administration of proton pump inhibitor pantoprazole. Biochimie. 2011;93:1786–1796.
  • Calcinotto A, Filipazzi P, Grioni M, et al. Modulation of microenvironment acidity reverses anergy in human and murine tumor-infiltrating T lymphocytes. Cancer Res. 2012;72:2746–2756.
  • Pascual-Pasto G, Olaciregui NG, Opezzo JAW, et al. Increased delivery of chemotherapy to the vitreous by inhibition of the blood-retinal barrier. J Control Release. 2017;264:34–44.
  • Chanchal SK, Mahajan UB, Siddharth S, et al. In vivo and in vitro protective effects of omeprazole against neuropathic pain. Sci Rep. 2016;6:30007.
  • Fais S, Luciani F Novel Uses For Proton Pump Inhibitors. International application number: PCT/EP2005/002250. International publication number: WO 2005/077365 (25.08.2005 Gazette 2005/34).
  • Iessi E, Logozzi M, Mizzoni D, et al. Rethinking the combination of proton exchanger inhibitors in cancer therapy. Metabolites 2017 Dec 23;8(1):E2.
  • Azzarito T, Lugini L, Spugnini EP, et al. Effect of modified alkaline supplementation on syngenic melanoma growth in CB57/BL Mice. PLoS One. 2016;1:e0159763.
  • Astigiano S, Puglisi A, Mastracci L, et al. Systemic alkalinisation delays prostate cancer cell progression in TRAMP mice. J Enzyme Inhib Med Chem. 2017;32:363–368.
  • Bruno G, Zaccari P, Rocco G, et al. Proton pump inhibitors and dysbiosis: current knowledge and aspects to be clarified. World J Gastroenterol. 2019;25:2706–2719.
  • Kuchuk O, Tuccitto A, Citterio D, et al. pH regulators to target the tumor immune microenvironment in human hepatocellular carcinoma. Oncoimmunology. 2018 Mar 26;7(7):e1445452.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.