{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T17:24:53Z","timestamp":1780507493083,"version":"3.54.1"},"reference-count":50,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,9,15]],"date-time":"2020-09-15T00:00:00Z","timestamp":1600128000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,9,15]],"date-time":"2020-09-15T00:00:00Z","timestamp":1600128000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100005010","name":"Associazione Italiana per la Ricerca sul Cancro","doi-asserted-by":"publisher","award":["IG15216"],"award-info":[{"award-number":["IG15216"]}],"id":[{"id":"10.13039\/501100005010","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005010","name":"Associazione Italiana per la Ricerca sul Cancro","doi-asserted-by":"publisher","award":["IG17009"],"award-info":[{"award-number":["IG17009"]}],"id":[{"id":"10.13039\/501100005010","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009880","name":"Regione Lazio","doi-asserted-by":"publisher","award":["n.85-2017-13750"],"award-info":[{"award-number":["n.85-2017-13750"]}],"id":[{"id":"10.13039\/501100009880","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cell Commun Signal"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>Target therapies based on BRAF and MEK inhibitors (MAPKi) have changed the therapeutic landscape for metastatic melanoma patients bearing mutations in the BRAF kinase. However, the emergence of drug resistance imposes the necessity to conceive novel therapeutic strategies capable to achieve a more durable disease control. In the last years, retrotransposons laying in human genome have been shown to undergo activation during tumorigenesis, where they contribute to genomic instability. Their activation can be efficiently controlled with reverse transcriptase inhibitors (RTIs) frequently used in the treatment of AIDS. These drugs have demonstrated anti-proliferative effects in several cancer models, including also metastatic melanoma. However, to our knowledge no previous study investigated the capability of RTIs to mitigate drug resistance to target therapy in BRAF-mutant melanomas. In this short report we show that the non-nucleoside RTI, SPV122 in combination with MAPKi strongly inhibits BRAF-mutant melanoma cell growth, induces apoptosis, and delays the emergence of resistance to target therapy in vitro. Mechanistically, this combination strongly induces DNA double-strand breaks, mitochondrial membrane depolarization and increased ROS levels. Our results shed further light on the molecular activity of RTI in melanoma and pave the way to their use as a novel therapeutic option to improve the efficacy of target therapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Graphical abstract<\/jats:title>\n                  <\/jats:sec>","DOI":"10.1186\/s12964-020-00633-7","type":"journal-article","created":{"date-parts":[[2020,9,15]],"date-time":"2020-09-15T08:02:55Z","timestamp":1600156975000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Reverse transcriptase inhibition potentiates target therapy in BRAF-mutant melanomas: effects on cell proliferation, apoptosis, DNA-damage, ROS induction and mitochondrial membrane depolarization"],"prefix":"10.1186","volume":"18","author":[{"given":"Luigi","family":"Fattore","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debora","family":"Malpicci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ciro","family":"Milite","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina","family":"Castellano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianluca","family":"Sbardella","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerardo","family":"Botti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo A.","family":"Ascierto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rita","family":"Mancini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gennaro","family":"Ciliberto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,9,15]]},"reference":[{"key":"633_CR1","doi-asserted-by":"publisher","first-page":"35","DOI":"10.2147\/ITT.S134842","volume":"7","author":"B Domingues","year":"2018","unstructured":"Domingues B, Lopes JM, Soares P, P\u00f3pulo H. Melanoma treatment in review. Immunotargets Ther. 2018;7:35\u201349.","journal-title":"Immunotargets Ther"},{"issue":"5","key":"633_CR2","doi-asserted-by":"publisher","first-page":"603","DOI":"10.1016\/S1470-2045(18)30142-6","volume":"19","author":"R Dummer","year":"2018","unstructured":"Dummer R, Ascierto PA, Gogas HJ, Arance A, Mandala M, Liszkay G, et al. Encorafenib plus binimetinib versus vemurafenib or encorafenib in patients with BRAF-mutant melanoma (COLUMBUS): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol. 2018;19(5):603\u201315.","journal-title":"Lancet Oncol"},{"key":"633_CR3","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1016\/j.cytogfr.2017.05.003","volume":"36","author":"L Fattore","year":"2017","unstructured":"Fattore L, Sacconi A, Mancini R, Ciliberto G. MicroRNA-driven deregulation of cytokine expression helps development of drug resistance in metastatic melanoma. Cytokine Growth Factor Rev. 2017;36:39\u201348.","journal-title":"Cytokine Growth Factor Rev"},{"issue":"1","key":"633_CR4","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1158\/2159-8290.CD-17-0682","volume":"8","author":"A Hong","year":"2018","unstructured":"Hong A, Moriceau G, Sun L, Lomeli S, Piva M, Damoiseaux R, et al. Exploiting drug addiction mechanisms to select against MAPKi-resistant melanoma. Cancer Discov. 2018;8(1):74\u201393.","journal-title":"Cancer Discov"},{"issue":"6","key":"633_CR5","doi-asserted-by":"publisher","first-page":"1271","DOI":"10.1016\/j.cell.2015.07.061","volume":"162","author":"W Hugo","year":"2015","unstructured":"Hugo W, Shi H, Sun L, Piva M, Song C, Kong X, et al. Non-genomic and immune evolution of melanoma acquiring MAPKi resistance. Cell. 2015;162(6):1271\u201385.","journal-title":"Cell"},{"issue":"1","key":"633_CR6","doi-asserted-by":"publisher","first-page":"318","DOI":"10.1186\/s13046-018-0989-7","volume":"37","author":"ME Pisanu","year":"2018","unstructured":"Pisanu ME, Maugeri-Sacc\u00c3 M, Fattore L, Bruschini S, De Vitis C, Tabb\u00ec E, et al. Inhibition of Stearoyl-CoA desaturase 1 reverts BRAF and MEK inhibition-induced selection of cancer stem cells in BRAF-mutated melanoma. J Exp Clin Cancer Res. 2018;37(1):318.","journal-title":"J Exp Clin Cancer Res"},{"issue":"11","key":"633_CR7","doi-asserted-by":"publisher","first-page":"827-019-2048-5","DOI":"10.1038\/s41419-019-2048-5","volume":"10","author":"L Fattore","year":"2019","unstructured":"Fattore L, Ruggiero CF, Liguoro D, Mancini R, Ciliberto G. Single cell analysis to dissect molecular heterogeneity and disease evolution in metastatic melanoma. Cell Death Dis. 2019;10(11):827-019-2048-5.","journal-title":"Cell Death Dis"},{"issue":"10","key":"633_CR8","doi-asserted-by":"publisher","first-page":"1425","DOI":"10.3390\/cancers11101425","volume":"11","author":"CF Ruggiero","year":"2019","unstructured":"Ruggiero CF, Malpicci D, Fattore L, Madonna G, Vanella V, Mallardo D, et al. ErbB3 phosphorylation as central event in adaptive resistance to targeted therapy in metastatic melanoma: early detection in CTCs during therapy and insights into regulation by Autocrine Neuregulin. Cancers (Basel). 2019;11(10):1425. https:\/\/doi.org\/10.3390\/cancers11101425.","journal-title":"Cancers (Basel)"},{"issue":"34","key":"633_CR9","doi-asserted-by":"publisher","first-page":"E5005","DOI":"10.1073\/pnas.1607753113","volume":"113","author":"L Fattore","year":"2016","unstructured":"Fattore L, Mancini R, Acunzo M, Romano G, Lagan\u00c3 A, Pisanu ME, et al. miR-579-3p controls melanoma progression and resistance to target therapy. Proc Natl Acad Sci U S A. 2016;113(34):E5005\u201313.","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"7","key":"633_CR10","doi-asserted-by":"publisher","first-page":"1267","DOI":"10.1038\/s41418-018-0205-5","volume":"26","author":"L Fattore","year":"2019","unstructured":"Fattore L, Ruggiero CF, Pisanu ME, Liguoro D, Cerri A, Costantini S, et al. Reprogramming miRNAs global expression orchestrates development of drug resistance in BRAF mutated melanoma. Cell Death Diff. 2019;26(7):1267\u201382.","journal-title":"Cell Death Diff"},{"issue":"6","key":"633_CR11","doi-asserted-by":"publisher","first-page":"E1930","DOI":"10.3390\/ijms21061930","volume":"21","author":"L Fattore","year":"2020","unstructured":"Fattore L, Campani V, Ruggiero CF, Salvati V, Liguoro D, Scotti L, et al. In vitro biophysical and biological characterization of lipid nanoparticles co-encapsulating Oncosuppressors miR-199b-5p and miR-204-5p as Potentiators of target therapy in metastatic melanoma. Int J Mol Sci. 2020;21(6):E1930. https:\/\/doi.org\/10.3390\/ijms21061930.","journal-title":"Int J Mol Sci"},{"key":"633_CR12","doi-asserted-by":"publisher","first-page":"6","DOI":"10.3389\/fchem.2016.00006","volume":"4","author":"I Sciamanna","year":"2016","unstructured":"Sciamanna I, De Luca C, Spadafora C. The reverse transcriptase encoded by LINE-1 Retrotransposons in the genesis, progression, and therapy of Cancer. Front Chem. 2016;4:6.","journal-title":"Front Chem"},{"key":"633_CR13","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1016\/j.ejmech.2015.11.025","volume":"108","author":"M Bastos","year":"2016","unstructured":"Bastos M, Costa CCP, Bezerra TC, da Silva FC, Boechat N. Efavirenz a nonnucleoside reverse transcriptase inhibitor of first-generation: Approaches based on its medicinal chemistry. Eur J Med Chem. 2016;108:455\u201365.","journal-title":"Eur J Med Chem"},{"key":"633_CR14","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1186\/s13100-016-0070-z","volume":"7","author":"JL Goodier","year":"2016","unstructured":"Goodier JL. Restricting Retrotransposons: A review. Mob DNA. 2016;7:16. https:\/\/doi.org\/10.1186\/s13100-016-0070-z eCollection 2016.","journal-title":"Mob DNA"},{"issue":"11","key":"633_CR15","doi-asserted-by":"publisher","first-page":"2183","DOI":"10.1093\/annonc\/mdy413","volume":"29","author":"AS Attermann","year":"2018","unstructured":"Attermann AS, Bjerregaard A-M, Saini SK, Gr\u00f8nb\u00e6k K, Hadrup SR. Human endogenous retroviruses and their implication for Immunotherapeutics of Cancer. Ann Oncol. 2018;29(11):2183\u201391. https:\/\/doi.org\/10.1093\/annonc\/mdy413.","journal-title":"Ann Oncol"},{"key":"633_CR16","doi-asserted-by":"publisher","first-page":"2039","DOI":"10.3389\/fimmu.2018.02039","volume":"9","author":"N Grandi","year":"2018","unstructured":"Grandi N, Tramontano E. Human endogenous retroviruses are ancient acquired elements still shaping innate immune responses. Front Immunol. 2018;9:2039. https:\/\/doi.org\/10.3389\/fimmu.2018.02039 eCollection 2018.","journal-title":"Front Immunol"},{"issue":"3","key":"633_CR17","doi-asserted-by":"publisher","first-page":"e1003402","DOI":"10.1371\/journal.pgen.1003402","volume":"9","author":"N Rodi\u0107","year":"2013","unstructured":"Rodi\u0107 N, Burns KH. Long interspersed element-1 (LINE-1): passenger or driver in human neoplasms? PLoS Genet. 2013;9(3):e1003402.","journal-title":"PLoS Genet"},{"issue":"1","key":"633_CR18","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1016\/j.cell.2013.02.032","volume":"153","author":"R Shukla","year":"2013","unstructured":"Shukla R, Upton KR, Mu\u00f1oz-Lopez M, Gerhardt DJ, Fisher ME, Nguyen T, et al. Endogenous retrotransposition activates oncogenic pathways in hepatocellular carcinoma. Cell. 2013;153(1):101\u201311.","journal-title":"Cell"},{"issue":"1","key":"633_CR19","doi-asserted-by":"publisher","first-page":"4022","DOI":"10.1038\/s41467-019-11770-0","volume":"10","author":"T Cajuso","year":"2019","unstructured":"Cajuso T, Sulo P, Tanskanen T, Katainen R, Taira A, H\u00e4nninen UA, et al. Retrotransposon insertions can initiate colorectal cancer and are associated with poor survival. Nat Commun. 2019;10(1):4022.","journal-title":"Nat Commun"},{"issue":"6","key":"633_CR20","doi-asserted-by":"publisher","first-page":"745","DOI":"10.1101\/gr.201814.115","volume":"26","author":"EC Scott","year":"2016","unstructured":"Scott EC, Gardner EJ, Masood A, Chuang NT, Vertino PM, Devine SE. A hot L1 retrotransposon evades somatic repression and initiates human colorectal cancer. Genome Res. 2016;26(6):745\u201355.","journal-title":"Genome Res"},{"issue":"1","key":"633_CR21","doi-asserted-by":"publisher","first-page":"9683","DOI":"10.1038\/s41598-019-46160-5","volume":"9","author":"D Cheng","year":"2019","unstructured":"Cheng D, Zhao Y, Zhang F, Zhang J, Wang S, Zhu J. Engineering a humanized telomerase reverse transcriptase gene in mouse embryonic stem cells. Sci Rep. 2019;9(1):9683. https:\/\/doi.org\/10.1038\/s41598-019-46160-5.","journal-title":"Sci Rep"},{"issue":"1","key":"633_CR22","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1186\/s13073-016-0324-x","volume":"8","author":"MA Jafri","year":"2016","unstructured":"Jafri MA, Ansari SA, Alqahtani MH, Shay JW. Roles of telomeres and telomerase in Cancer, and advances in telomerase-targeted therapies. Genome Med. 2016;8(1):69. https:\/\/doi.org\/10.1186\/s13073-016-0324-x.","journal-title":"Genome Med"},{"issue":"2","key":"633_CR23","first-page":"1728","volume":"15","author":"M Hecht","year":"2018","unstructured":"Hecht M, Harrer T, K\u00f6rber V, Sarpong EO, Moser F, Fiebig N, et al. Cytotoxic effect of Efavirenz in BxPC-3 pancreatic cancer cells is based on oxidative stress and is synergistic with ionizing radiation. Oncol Lett. 2018;15(2):1728\u201336.","journal-title":"Oncol Lett"},{"issue":"1","key":"633_CR24","doi-asserted-by":"publisher","first-page":"617","DOI":"10.3892\/or.2016.5243","volume":"37","author":"A Br\u00fcning","year":"2017","unstructured":"Br\u00fcning A, J\u00fcckstock J, Kost B, Tsikouras P, Weissenbacher T, Mahner S, et al. Induction of DNA damage and apoptosis in human leukemia cells by efavirenz. Oncol Rep. 2017;37(1):617\u201321.","journal-title":"Oncol Rep"},{"issue":"12","key":"633_CR25","doi-asserted-by":"publisher","first-page":"e14221","DOI":"10.1371\/journal.pone.0014221","volume":"5","author":"F Carlini","year":"2010","unstructured":"Carlini F, Ridolfi B, Molinari A, Parisi C, Bozzuto G, Toccacieli L, et al. The reverse transcription inhibitor abacavir shows anticancer activity in prostate cancer cell lines. PLoS One. 2010;5(12):e14221.","journal-title":"PLoS One"},{"issue":"1","key":"633_CR26","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1593\/neo.11426","volume":"14","author":"T Aschacher","year":"2012","unstructured":"Aschacher T, Sampl S, K\u00e4ser L, Bernhard D, Spittler A, Holzmann K, et al. The combined use of known antiviral reverse transcriptase inhibitors AZT and DDI induce anticancer effects at low concentrations. Neoplasia. 2012;14(1):44\u201353.","journal-title":"Neoplasia"},{"issue":"22","key":"633_CR27","doi-asserted-by":"publisher","first-page":"6776","DOI":"10.1021\/jm0507330","volume":"48","author":"S Bartolini","year":"2005","unstructured":"Bartolini S, Mai A, Artico M, Paesano N, Rotili D, Spadafora C, et al. 6-[1-(2,6-Difluorophenyl)ethyl] pyrimidinones antagonize cell proliferation and induce cell differentiation by inhibiting (A Nontelomeric) endogenous reverse transcriptase. J Med Chem. 2005;48(22):6776\u20138.","journal-title":"J Med Chem"},{"issue":"10","key":"633_CR28","doi-asserted-by":"publisher","first-page":"1073","DOI":"10.1002\/cmdc.200600139","volume":"1","author":"G Sbardella","year":"2006","unstructured":"Sbardella G, Bartolini S, Castellano S, Artico M, Paesano N, Rotili D, et al. 6-alkylthio-4-[1-(2,6-difluorophenyl)alkyl]-1H-[1,3,5]triazin-2-ones (ADATs): novel regulators of cell differentiation and proliferation. ChemMedChem. 2006;1(10):1073\u201380.","journal-title":"ChemMedChem"},{"issue":"16","key":"633_CR29","doi-asserted-by":"publisher","first-page":"5927","DOI":"10.1021\/jm200734j","volume":"54","author":"G Sbardella","year":"2011","unstructured":"Sbardella G, Mai A, Bartolini S, Castellano S, Cirilli R, Rotili D, et al. Modulation of cell differentiation, proliferation, and tumor growth by dihydrobenzyloxopyrimidine non-nucleoside reverse transcriptase inhibitors. J Med Chem. 2011;54(16):5927\u201336.","journal-title":"J Med Chem"},{"key":"633_CR30","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1016\/j.canlet.2020.02.029","volume":"478","author":"C Bellisai","year":"2020","unstructured":"Bellisai C, Sciamanna I, Rovella P, Giovannini D, Baranzini M, Pugliese GM, et al. Reverse transcriptase inhibitors promote the remodelling of nuclear architecture and induce autophagy in prostate cancer cells. Cancer Lett. 2020;478:133\u201345.","journal-title":"Cancer Lett"},{"issue":"3","key":"633_CR31","doi-asserted-by":"publisher","first-page":"1877","DOI":"10.1002\/jcp.29121","volume":"235","author":"S Bruschini","year":"2020","unstructured":"Bruschini S, di Martino S, Pisanu ME, Fattore L, De Vitis C, Laquintana V, et al. CytoMatrix for a reliable and simple characterization of lung cancer stem cells from malignant pleural effusions. J Cell Physiol. 2020;235(3):1877\u201387.","journal-title":"J Cell Physiol"},{"issue":"7","key":"633_CR32","doi-asserted-by":"publisher","first-page":"993","DOI":"10.1038\/sj.onc.1209863","volume":"26","author":"S Burdak-Rothkamm","year":"2007","unstructured":"Burdak-Rothkamm S, Short SC, Folkard M, Rothkamm K, Prise KM. ATR-dependent radiation-induced gamma H2AX foci in bystander primary human astrocytes and glioma cells. Oncogene. 2007;26(7):993\u20131002.","journal-title":"Oncogene"},{"issue":"11","key":"633_CR33","doi-asserted-by":"publisher","first-page":"1928","DOI":"10.3390\/jcm8111928","volume":"8","author":"C De Vitis","year":"2019","unstructured":"De Vitis C, Corleone G, Salvati V, Ascenzi F, Pallocca M, De Nicola F, et al. B4GALT1 is a new candidate to maintain the Stemness of lung Cancer stem cells. J Clin Med. 2019;8(11):1928. https:\/\/doi.org\/10.3390\/jcm8111928.","journal-title":"J Clin Med"},{"issue":"24","key":"633_CR34","doi-asserted-by":"publisher","first-page":"3923","DOI":"10.1038\/sj.onc.1208562","volume":"24","author":"I Sciamanna","year":"2005","unstructured":"Sciamanna I, Landriscina M, Pittoggi C, Quirino M, Mearelli C, Beraldi R, et al. Inhibition of endogenous reverse transcriptase antagonizes human tumor growth. Oncogene. 2005;24(24):3923\u201331. https:\/\/doi.org\/10.1038\/sj.onc.1208562.","journal-title":"Oncogene."},{"issue":"3","key":"633_CR35","doi-asserted-by":"publisher","first-page":"4147","DOI":"10.18632\/oncotarget.13792","volume":"8","author":"L Lugini","year":"2017","unstructured":"Lugini L, Sciamanna I, Federici C, Iessi E, Spugnini EP, Fais S. Antitumor effect of combination of the inhibitors of two new oncotargets: proton pumps and reverse transcriptase. Oncotarget. 2017;8(3):4147\u201355. https:\/\/doi.org\/10.18632\/oncotarget.13792.","journal-title":"Oncotarget"},{"issue":"1","key":"633_CR36","doi-asserted-by":"publisher","first-page":"5191","DOI":"10.1038\/s41467-019-12929-5","volume":"10","author":"I Salguero","year":"2019","unstructured":"Salguero I, Belotserkovskaya R, Coates J, Sczaniecka-Clift M, Demir M, Jhujh S, et al. MDC1 PST-repeat region promotes histone H2AX-independent chromatin association and DNA damage tolerance. Nat Commun. 2019;10(1):5191.","journal-title":"Nat Commun"},{"issue":"9","key":"633_CR37","doi-asserted-by":"publisher","first-page":"e0183932","DOI":"10.1371\/journal.pone.0183932","volume":"12","author":"AM Lustri","year":"2017","unstructured":"Lustri AM, Di Matteo S, Fraveto A, Costantini D, Cantafora A, Napoletano C, et al. TGF-\u00ce2 signaling is an effective target to impair survival and induce apoptosis of human cholangiocarcinoma cells: A study on human primary cell cultures. PLoS One. 2017;12(9):e0183932.","journal-title":"PLoS One"},{"key":"633_CR38","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1146\/annurev-genet-102108-134850","volume":"43","author":"C Wang","year":"2009","unstructured":"Wang C, Youle RJ. The role of mitochondria in apoptosis*. Annu Rev Genet. 2009;43:95\u2013118.","journal-title":"Annu Rev Genet"},{"issue":"1","key":"633_CR39","doi-asserted-by":"publisher","first-page":"4363","DOI":"10.1038\/s41598-020-61381-9","volume":"10","author":"SN Dijk","year":"2020","unstructured":"Dijk SN, Protasoni M, Elpidorou M, Kroon AM, Taanman J. Mitochondria as target to inhibit proliferation and induce apoptosis of cancer cells: the effects of doxycycline and gemcitabine. Scientific Rep. 2020;10(1):4363.","journal-title":"Scientific Rep"},{"issue":"2","key":"633_CR40","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1016\/j.freeradbiomed.2008.10.023","volume":"46","author":"DM Mattson","year":"2009","unstructured":"Mattson DM, Ahmad IM, Dayal D, Parsons AD, Aykin-Burns N, Li L, et al. Cisplatin combined with Zidovudine enhances cytotoxicity and oxidative stress in human head and neck Cancer cells via a Thiol-dependent mechanism. Free Radic Biol Med. 2009;46(2):232\u20137. https:\/\/doi.org\/10.1016\/j.freeradbiomed.2008.10.023 Epub 2008 Oct 18.","journal-title":"Free Radic Biol Med"},{"issue":"1","key":"633_CR41","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s12012-008-9029-8","volume":"9","author":"ER Kline","year":"2009","unstructured":"Kline ER, Bassit L, Hernandez-Santiago BI, Detorio MA, Liang B, Kleinhenz DJ, et al. Long-term exposure to AZT, but not d4T, increases endothelial cell oxidative stress and mitochondrial dysfunction. Cardiovasc Toxicol. 2009;9(1):1\u201312. https:\/\/doi.org\/10.1007\/s12012-008-9029-8 Epub 2008 Dec 9.","journal-title":"Cardiovasc Toxicol"},{"key":"633_CR42","doi-asserted-by":"publisher","first-page":"6016278","DOI":"10.1155\/2019\/6016278","volume":"2019","author":"E Bayurova","year":"2019","unstructured":"Bayurova E, Jansons J, Skrastina D, Smirnova O, Mezale D, Kostyusheva A, et al. HIV-1 reverse transcriptase promotes tumor growth and metastasis formation via ROS-dependent upregulation of twist. Oxid Med Cell Longev. 2019;2019:6016278.","journal-title":"Oxid Med Cell Longev"},{"key":"633_CR43","first-page":"5381692","volume":"2019","author":"SJ Kim","year":"2019","unstructured":"Kim SJ, Kim HS, Seo YR. Understanding of ROS-inducing strategy in anticancer therapy. Oxid Med Cell Longev. 2019;2019:5381692.","journal-title":"Oxid Med Cell Longev"},{"key":"633_CR44","doi-asserted-by":"publisher","first-page":"8201642","DOI":"10.1155\/2016\/8201642","volume":"2016","author":"W Ma","year":"2016","unstructured":"Ma W, Hong Z, Liu H, Chen X, Ding L, Liu Z, et al. Human endogenous retroviruses-K (HML-2) expression is correlated with prognosis and Progress of hepatocellular carcinoma. Biomed Res Int. 2016;2016:8201642. https:\/\/doi.org\/10.1155\/2016\/8201642 Epub 2016 Dec 14.","journal-title":"Biomed Res Int"},{"issue":"23","key":"633_CR45","doi-asserted-by":"publisher","first-page":"e01309","DOI":"10.1128\/JVI.01309-17","volume":"91","author":"R Contreras-Galindo","year":"2017","unstructured":"Contreras-Galindo R, Dube D, Fujinaga K, Kaplan MH, Markovitz DM. Susceptibility of human endogenous retrovirus type K to reverse transcriptase inhibitors. J Virol. 2017;91(23):e01309\u201317. https:\/\/doi.org\/10.1128\/JVI.01309-17 Print 2017 Dec 1.","journal-title":"J Virol"},{"issue":"6","key":"633_CR46","doi-asserted-by":"publisher","first-page":"584","DOI":"10.1158\/2159-8290.CD-16-0062","volume":"6","author":"JW Shay","year":"2016","unstructured":"Shay JW. Role of telomeres and telomerase in aging and Cancer. Cancer Discov. 2016;6(6):584\u201393. https:\/\/doi.org\/10.1158\/2159-8290.CD-16-0062 Epub 2016 Mar 30.","journal-title":"Cancer Discov"},{"issue":"1","key":"633_CR47","doi-asserted-by":"publisher","first-page":"579","DOI":"10.1038\/s41467-018-03033-1","volume":"9","author":"R Liu","year":"2018","unstructured":"Liu R, Zhang T, Zhu G, Xing M. Regulation of mutant TERT by BRAF V600E\/MAP kinase pathway through FOS\/GABP in human Cancer. Nat Commun. 2018;9(1):579. https:\/\/doi.org\/10.1038\/s41467-018-03033-1.","journal-title":"Nat Commun"},{"key":"633_CR48","doi-asserted-by":"publisher","first-page":"202004707","DOI":"10.1073\/pnas.2004707117","volume":"19","author":"J Tan","year":"2020","unstructured":"Tan J, Liu R, Zhu G, Umbricht CB, Xing M. TERT promoter mutation determines apoptotic and therapeutic responses of BRAF-mutant cancers to BRAF and MEK inhibitors: Achilles heel. Proc Natl Acad Sci U S A. 2020;19:202004707. https:\/\/doi.org\/10.1073\/pnas.2004707117.","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"11","key":"633_CR49","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0047505","volume":"7","author":"KR Hukezalie","year":"2012","unstructured":"Hukezalie KR, Thumati NR, C\u00f4t\u00e9 HCF, Wong JMY. 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(11):e47505. https:\/\/doi.org\/10.1371\/journal.pone.0047505.","journal-title":"PLoS One"},{"key":"633_CR50","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1038\/nrc.2017.35","volume":"17","author":"KH Burns","year":"2017","unstructured":"Burns KH. Transposable elements in cancer. Nat Rev Cancer. 2017;17:415\u201324. https:\/\/doi.org\/10.1038\/nrc.2017.35.","journal-title":"Nat Rev Cancer"}],"container-title":["Cell Communication and Signaling"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12964-020-00633-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12964-020-00633-7\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12964-020-00633-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,14]],"date-time":"2021-09-14T19:32:50Z","timestamp":1631647970000},"score":1,"resource":{"primary":{"URL":"https:\/\/biosignaling.biomedcentral.com\/articles\/10.1186\/s12964-020-00633-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9,15]]},"references-count":50,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2020,12]]}},"alternative-id":["633"],"URL":"https:\/\/doi.org\/10.1186\/s12964-020-00633-7","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-25504\/v2","asserted-by":"object"},{"id-type":"doi","id":"10.21203\/rs.3.rs-25504\/v1","asserted-by":"object"}]},"ISSN":["1478-811X"],"issn-type":[{"value":"1478-811X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,9,15]]},"assertion":[{"value":"28 April 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 July 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 September 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Not applicable.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"All The authors declare no conflict of interest with the exception of P.A.A. P.A.A. has advisory\/consultant role for BMS, Roche-Genentech, MSD, Array, Novartis, Merck Serono, Pierre Fabre, Incyte, Genmab, Newlink Genetics, Medimmune, AstraZeneca, Syndax, Sun Pharma, Sanofi, Idera, Ultimovacs, Sandoz, Immunocore, 4SC, Alkermes, Italfarmaco. P.A.A. receives research funds from BMS, Roche-Genentech, Array and travel support from MSD. The funders of this study had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"150"}}