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Current Drug Delivery

Editor-in-Chief

ISSN (Print): 1567-2018
ISSN (Online): 1875-5704

Research Article

Drugs in the GIST Field (Therapeutic Targets and Clinical Trial Staging)

Author(s): Chen Huang, Xinli Ma, Ming Wang and Hui Cao*

Volume 21, Issue 1, 2024

Published on: 26 December, 2022

Page: [80 - 90] Pages: 11

DOI: 10.2174/1567201820666221122120657

Price: $65

Abstract

Background: Molecular targeted therapies are the most important type of medical treatment for GIST, but the development of GIST drugs and their targets have not been summarized.

Methods: Drugs in the field of GIST were analyzed and collated through Pharmaprojects, ClinicalTrials. gov and PharmaGO databases.

Results: As of 2021, there are 75 drugs that have appeared in the GIST clinical trials. The six most frequent targets in GIST clinical trials, in descending order of frequency, were KIT, PDGFRA, KDR (VEGFR2), FLT3, FLT1 (VEGFR1), and FLT4/VEGFR3. Only 8 drugs are in preclinical research. There are challenges in the development of new drugs for GIST.

Conclusion: This article analyzes and summarizes the general situation of GIST drugs, the target distribution of GIST drugs, and the trends in GIST drug-related clinical trials.

« Previous
[1]
Blay, J.Y.; Kang, Y.K.; Nishida, T.; von Mehren, M. Gastrointestinal stromal tumours. Nat. Rev. Dis. Primers, 2021, 7(1), 22.
[http://dx.doi.org/10.1038/s41572-021-00254-5] [PMID: 33737510]
[2]
Serrano, C.; George, S. Gastrointestinal stromal tumor: Challenges and opportunities for a new decade. Clin. Cancer Res., 2020, 26(19), 5078-5085.
[http://dx.doi.org/10.1158/1078-0432.CCR-20-1706] [PMID: 32601076]
[3]
Wang, Y.; Call, J. Mutational testing in gastrointestinal stromal tumor. Curr. Cancer Drug Targets, 2019, 19(9), 688-697.
[http://dx.doi.org/10.2174/1568009619666190326123945] [PMID: 30914028]
[4]
Klug, L.R.; Khosroyani, H.M.; Kent, J.D.; Heinrich, M.C. New treatment strategies for advanced-stage gastrointestinal stromal tumours. Nat. Rev. Clin. Oncol., 2022, 19(5), 328-341.
[http://dx.doi.org/10.1038/s41571-022-00606-4] [PMID: 35217782]
[5]
Casali, P.G.; Abecassis, N.; Bauer, S.; Biagini, R.; Bielack, S.; Bonvalot, S.; Boukovinas, I.; Bovee, J.V.M.G.; Brodowicz, T.; Broto, J.M.; Buonadonna, A.; De Álava, E.; Dei Tos, A.P.; Del Muro, X.G.; Dileo, P.; Eriksson, M.; Fedenko, A.; Ferraresi, V.; Ferrari, A.; Ferrari, S.; Frezza, A.M.; Gasperoni, S.; Gelderblom, H.; Gil, T.; Grignani, G.; Gronchi, A.; Haas, R.L.; Hannu, A.; Hassan, B.; Hohenberger, P.; Issels, R.; Joensuu, H.; Jones, R.L.; Judson, I.; Jutte, P.; Kaal, S.; Kasper, B.; Kopeckova, K.; Krákorová, D.A.; Le Cesne, A.; Lugowska, I.; Merimsky, O.; Montemurro, M.; Pantaleo, M.A.; Piana, R.; Picci, P.; Piperno-Neumann, S.; Pousa, A.L.; Reichardt, P.; Robinson, M.H.; Rutkowski, P.; Safwat, A.A.; Schöffski, P.; Sleijfer, S.; Stacchiotti, S.; Sundby Hall, K.; Unk, M.; Van Coevorden, F.; Van der Graaf, W.; Whelan, J.; Wardelmann, E.; Zaikova, O.; Blay, J.Y. Gastrointestinal stromal tumours: ESMO–EURACAN Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann. Oncol., 2018, 29(Suppl. 4), iv68-iv78.
[http://dx.doi.org/10.1093/annonc/mdy095] [PMID: 29846513]
[6]
Falkenhorst, J.; Hamacher, R.; Bauer, S. New therapeutic agents in gastrointestinal stromal tumours. Curr. Opin. Oncol., 2019, 31(4), 322-328.
[http://dx.doi.org/10.1097/CCO.0000000000000549] [PMID: 31033566]
[7]
Buchdunger, E.; Zimmermann, J.; Mett, H.; Meyer, T.; Müller, M.; Druker, B.J.; Lydon, N.B. Inhibition of the Abl protein-tyrosine kinase in vitro and in vivo by a 2-phenylaminopyrimidine derivative. Cancer Res., 1996, 56(1), 100-104.
[PMID: 8548747]
[8]
Druker, B.J.; Tamura, S.; Buchdunger, E.; Ohno, S.; Segal, G.M.; Fanning, S.; Zimmermann, J.; Lydon, N.B. Effects of a selective inhibitor of the Abl tyrosine kinase on the growth of Bcr–Abl positive cells. Nat. Med., 1996, 2(5), 561-566.
[http://dx.doi.org/10.1038/nm0596-561] [PMID: 8616716]
[9]
Patel, S. Long-term efficacy of imatinib for treatment of metastatic GIST. Cancer Chemother. Pharmacol., 2013, 72(2), 277-286.
[http://dx.doi.org/10.1007/s00280-013-2135-8] [PMID: 23503753]
[10]
Vener, C.; Banzi, R.; Ambrogi, F.; Ferrero, A.; Saglio, G.; Pravettoni, G.; Sant, M. First-line imatinib vs. second- and third-generation TKIs for chronic-phase CML: A systematic review and meta-analysis. Blood Adv., 2020, 4(12), 2723-2735.
[http://dx.doi.org/10.1182/bloodadvances.2019001329] [PMID: 32559295]
[11]
Izzedine, H.; Buhaescu, I.; Rixe, O.; Deray, G. Sunitinib malate. Cancer Chemother. Pharmacol., 2007, 60(3), 357-364.
[http://dx.doi.org/10.1007/s00280-006-0376-5] [PMID: 17136543]
[12]
Ikezoe, T.; Yang, Y.; Nishioka, C.; Bandobashi, K.; Nakatani, H.; Taguchi, T.; Koeffler, H.P.; Taguchi, H. Effect of SU11248 on gastrointestinal stromal tumor-T1 cells: Enhancement of growth inhibition via inhibition of 3-kinase/Akt/mammalian target of rapamycin signaling. Cancer Sci., 2006, 97(9), 945-951.
[http://dx.doi.org/10.1111/j.1349-7006.2006.00263.x] [PMID: 16916320]
[13]
O’Farrell, A.M.; Abrams, T.J.; Yuen, H.A.; Ngai, T.J.; Louie, S.G.; Yee, K.W.H.; Wong, L.M.; Hong, W.; Lee, L.B.; Town, A.; Smolich, B.D.; Manning, W.C.; Murray, L.J.; Heinrich, M.C.; Cherrington, J.M. SU11248 is a novel FLT3 tyrosine kinase inhibitor with potent activity in vitro and in vivo. Blood, 2003, 101(9), 3597-3605.
[http://dx.doi.org/10.1182/blood-2002-07-2307] [PMID: 12531805]
[14]
Rini, B.I.; Plimack, E.R.; Stus, V.; Gafanov, R.; Hawkins, R.; Nosov, D.; Pouliot, F.; Alekseev, B.; Soulières, D.; Melichar, B.; Vynnychenko, I.; Kryzhanivska, A.; Bondarenko, I.; Azevedo, S.J.; Borchiellini, D.; Szczylik, C.; Markus, M.; McDermott, R.S.; Bedke, J.; Tartas, S.; Chang, Y.H.; Tamada, S.; Shou, Q.; Perini, R.F.; Chen, M.; Atkins, M.B.; Powles, T. Pembrolizumab plus axitinib versus sunitinib for advanced renal-cell carcinoma. N. Engl. J. Med., 2019, 380(12), 1116-1127.
[http://dx.doi.org/10.1056/NEJMoa1816714] [PMID: 30779529]
[15]
Nemunaitis, J.; Bauer, S.; Blay, J.Y.; Choucair, K.; Gelderblom, H.; George, S.; Schöffski, P.; Mehren, M.; Zalcberg, J.; Achour, H.; Ruiz-Soto, R.; Heinrich, M.C. Intrigue: Phase III study of ripretinib versus sunitinib in advanced gastrointestinal stromal tumor after imatinib. Future Oncol., 2020, 16(1), 4251-4264.
[http://dx.doi.org/10.2217/fon-2019-0633] [PMID: 31755321]
[16]
Wilhelm, S.M.; Dumas, J.; Adnane, L.; Lynch, M.; Carter, C.A.; Schütz, G.; Thierauch, K.H.; Zopf, D. Regorafenib (BAY 73-4506): A new oral multikinase inhibitor of angiogenic, stromal and oncogenic receptor tyrosine kinases with potent preclinical antitumor activity. Int. J. Cancer, 2011, 129(1), 245-255.
[http://dx.doi.org/10.1002/ijc.25864] [PMID: 21170960]
[17]
Strumberg, D.; Schultheis, B. Regorafenib for cancer. Expert Opin. Investig. Drugs, 2012, 21(6), 879-889.
[http://dx.doi.org/10.1517/13543784.2012.684752] [PMID: 22577890]
[18]
Berndsen, R.H.; Castrogiovanni, C.; Weiss, A.; Rausch, M.; Dallinga, M.G.; Miljkovic-Licina, M.; Klaassen, I.; Meraldi, P.; van Beijnum, J.R.; Nowak-Sliwinska, P. Anti-angiogenic effects of crenolanib are mediated by mitotic modulation independently of PDGFR expression. Br. J. Cancer, 2019, 121(2), 139-149.
[http://dx.doi.org/10.1038/s41416-019-0498-2] [PMID: 31235865]
[19]
Kang, Y.K.; George, S.; Jones, R.L.; Rutkowski, P.; Shen, L.; Mir, O.; Patel, S.; Zhou, Y.; von Mehren, M.; Hohenberger, P.; Villalobos, V.; Brahmi, M.; Tap, W.D.; Trent, J.; Pantaleo, M.A.; Schöffski, P.; He, K.; Hew, P.; Newberry, K.; Roche, M.; Heinrich, M.C.; Bauer, S. Avapritinib versus regorafenib in locally advanced unresectable or metastatic gi stromal tumor: A randomized, open-label phase iii study. J. Clin. Oncol., 2021, 39(28), 3128-3139.
[http://dx.doi.org/10.1200/JCO.21.00217] [PMID: 34343033]
[20]
Smith, B.D.; Kaufman, M.D.; Lu, W.P.; Gupta, A.; Leary, C.B.; Wise, S.C.; Rutkoski, T.J.; Ahn, Y.M.; Al-Ani, G.; Bulfer, S.L.; Caldwell, T.M.; Chun, L.; Ensinger, C.L.; Hood, M.M.; McKinley, A.; Patt, W.C.; Ruiz-Soto, R.; Su, Y.; Telikepalli, H.; Town, A.; Turner, B.A.; Vogeti, L.; Vogeti, S.; Yates, K.; Janku, F.; Abdul Razak, A.R.; Rosen, O.; Heinrich, M.C.; Flynn, D.L. Ripretinib (dcc-2618) is a switch control kinase inhibitor of a broad spectrum of oncogenic and drug-resistant kit and pdgfra variants. Cancer Cell, 2019, 35(5), 738-751.e9.
[http://dx.doi.org/10.1016/j.ccell.2019.04.006] [PMID: 31085175]
[21]
Blu-285, dcc-2618 show activity against gist. Cancer Discov., 2017, 7(2), 121-122.
[http://dx.doi.org/10.1158/2159-8290.CD-NB2016-165] [PMID: 28077435]
[22]
Lostes-Bardaji, M.J.; García-Illescas, D.; Valverde, C.; Serrano, C. Ripretinib in gastrointestinal stromal tumor: the long-awaited step forward. Ther. Adv. Med. Oncol., 2021, 13, 1758835920986498.
[http://dx.doi.org/10.1177/1758835920986498] [PMID: 33473249]
[23]
Gardino, A.K.; Evans, E.K.; Kim, J.L.; Brooijmans, N.; Hodous, B.L.; Wolf, B.; Lengauer, C. Targeting kinases with precision. Mol. Cell. Oncol., 2018, 5(3), e1435183.
[http://dx.doi.org/10.1080/23723556.2018.1435183] [PMID: 30250891]
[24]
Garcia, J.; Hurwitz, H.I.; Sandler, A.B.; Miles, D.; Coleman, R.L.; Deurloo, R.; Chinot, O.L. Bevacizumab (Avastin®) in cancer treatment: A review of 15 years of clinical experience and future outlook. Cancer Treat. Rev., 2020, 86, 102017.
[http://dx.doi.org/10.1016/j.ctrv.2020.102017] [PMID: 32335505]
[25]
Ferrara, N.; Hillan, K.J.; Gerber, H.P.; Novotny, W. Discovery and development of bevacizumab, an anti-VEGF antibody for treating cancer. Nat. Rev. Drug Discov., 2004, 3(5), 391-400.
[http://dx.doi.org/10.1038/nrd1381] [PMID: 15136787]
[26]
Zhou, Q.; Xu, C.R.; Cheng, Y.; Liu, Y.P.; Chen, G.Y.; Cui, J.W.; Yang, N.; Song, Y.; Li, X.L.; Lu, S.; Zhou, J.Y.; Ma, Z.Y.; Yu, S.Y.; Huang, C.; Shu, Y.Q.; Wang, Z.; Yang, J.J.; Tu, H.Y.; Zhong, W.Z.; Wu, Y.L. Bevacizumab plus erlotinib in Chinese patients with untreated, EGFR-mutated, advanced NSCLC (ARTEMIS-CTONG1509): A multicenter phase 3 study. Cancer Cell, 2021, 39(9), 1279-1291.e3.
[http://dx.doi.org/10.1016/j.ccell.2021.07.005] [PMID: 34388377]
[27]
Heinrich, M.C.; Griffith, D.; McKinley, A.; Patterson, J.; Presnell, A.; Ramachandran, A.; Debiec-Rychter, M. Crenolanib inhibits the drug-resistant PDGFRA D842V mutation associated with imatinib-resistant gastrointestinal stromal tumors. Clin. Cancer Res., 2012, 18(16), 4375-4384.
[http://dx.doi.org/10.1158/1078-0432.CCR-12-0625] [PMID: 22745105]
[28]
Martin-Broto, J.; Moura, D.S. New drugs in gastrointestinal stromal tumors. Curr. Opin. Oncol., 2020, 32(4), 314-320.
[http://dx.doi.org/10.1097/CCO.0000000000000642] [PMID: 32541319]
[29]
Ge, S.; Zhang, Q.; He, Q.; Zou, J.; Liu, X.; Li, N.; Tian, T.; Zhu, Y.; Gao, J.; Shen, L. Famitinib exerted powerful antitumor activity in human gastric cancer cells and xenografts. Oncol. Lett., 2016, 12(3), 1763-1768.
[http://dx.doi.org/10.3892/ol.2016.4909] [PMID: 27602110]
[30]
Xu, R.H.; Shen, L.; Wang, K.M.; Wu, G.; Shi, C.M.; Ding, K.F.; Lin, L.Z.; Wang, J.W.; Xiong, J.P.; Wu, C.P.; Li, J.; Liu, Y.P.; Wang, D.; Ba, Y.; Feng, J.P.; Bai, Y.X.; Bi, J.W.; Ma, L.W.; Lei, J.; Yang, Q.; Yu, H. Famitinib versus placebo in the treatment of refractory metastatic colorectal cancer: A multicenter, randomized, double-blinded, placebo-controlled, phase II clinical trial. Chin. J. Cancer, 2017, 36(1), 97.
[http://dx.doi.org/10.1186/s40880-017-0263-y] [PMID: 29273089]
[31]
Ostendorf, B.N.; le Coutre, P.; Kim, T.D.; Quintás-Cardama, A. Nilotinib. Recent Results Cancer Res., 2014, 201, 67-80.
[http://dx.doi.org/10.1007/978-3-642-54490-3_3] [PMID: 24756785]
[32]
Plosker, G.L.; Robinson, D.M. Nilotinib. Drugs, 2008, 68(4), 449-459.
[http://dx.doi.org/10.2165/00003495-200868040-00005] [PMID: 18318563]
[33]
Meng, L.; Zhao, P.; Hu, Z.; Ma, W.; Niu, Y.; Su, J.; Zhang, Y. Nilotinib, a tyrosine kinase inhibitor, suppresses the cell growth and triggers autophagy in papillary thyroid cancer. Anticancer. Agents Med. Chem., 2022, 22(3), 596-602.
[http://dx.doi.org/10.2174/1871520621666210402110331] [PMID: 33797387]
[34]
Rosti, G.; Castagnetti, F.; Gugliotta, G.; Baccarani, M. Tyrosine kinase inhibitors in chronic myeloid leukaemia: Which, when, for whom? Nat. Rev. Clin. Oncol., 2017, 14(3), 141-154.
[http://dx.doi.org/10.1038/nrclinonc.2016.139] [PMID: 27752053]
[35]
Ohkubo, S.; Kodama, Y.; Muraoka, H.; Hitotsumachi, H.; Yoshimura, C.; Kitade, M.; Hashimoto, A.; Ito, K.; Gomori, A.; Takahashi, K.; Shibata, Y.; Kanoh, A.; Yonekura, K. TAS-116, a highly selective inhibitor of heat shock protein 90 α and β, demonstrates potent antitumor activity and minimal ocular toxicity in preclinical models. Mol. Cancer Ther., 2015, 14(1), 14-22.
[http://dx.doi.org/10.1158/1535-7163.MCT-14-0219] [PMID: 25416789]
[36]
Ranta-aho, S.; Piippo, N.; Korhonen, E.; Kaarniranta, K.; Hytti, M.; Kauppinen, A. Tas-116, a well-tolerated hsp90 inhibitor, prevents the activation of the nlrp3 inflammasome in human retinal pigment epithelial cells. Int. J. Mol. Sci., 2021, 22(9), 4875.
[http://dx.doi.org/10.3390/ijms22094875] [PMID: 34062977]
[37]
Shen, G.; Zheng, F.; Ren, D.; Du, F.; Dong, Q.; Wang, Z.; Zhao, F.; Ahmad, R.; Zhao, J. Anlotinib: A novel multi-targeting tyrosine kinase inhibitor in clinical development. J. Hematol. Oncol., 2018, 11(1), 120.
[http://dx.doi.org/10.1186/s13045-018-0664-7] [PMID: 30231931]
[38]
Gao, Y.; Liu, P.; Shi, R. Anlotinib as a molecular targeted therapy for tumors.(Review) Oncol. Lett., 2020, 20(2), 1001-1014.
[http://dx.doi.org/10.3892/ol.2020.11685] [PMID: 32724339]
[39]
Aoyama, T.; Yoshikawa, T. Apatinib — new third-line option for refractory gastric or GEJ cancer. Nat. Rev. Clin. Oncol., 2016, 13(5), 268-270.
[http://dx.doi.org/10.1038/nrclinonc.2016.53] [PMID: 27071350]
[40]
Peng, Z.; Wei, J.; Wang, F.; Ying, J.; Deng, Y.; Gu, K.; Cheng, Y.; Yuan, X.; Xiao, J.; Tai, Y.; Wang, L.; Zou, J.; Zhang, Y.; Shen, L. Camrelizumab combined with chemotherapy followed by camrelizumab plus apatinib as first-line therapy for advanced gastric or gastroesophageal junction adenocarcinoma. Clin. Cancer Res., 2021, 27(11), 3069-3078.
[http://dx.doi.org/10.1158/1078-0432.CCR-20-4691] [PMID: 33766817]
[41]
Gotlib, J.; Reiter, A.; Radia, D.H.; Deininger, M.W.; George, T.I.; Panse, J.; Vannucchi, A.M.; Platzbecker, U.; Alvarez-Twose, I.; Mital, A.; Hermine, O.; Dybedal, I.; Hexner, E.O.; Hicks, L.K.; Span, L.; Mesa, R.; Bose, P.; Pettit, K.M.; Heaney, M.L.; Oh, S.T.; Sen, J.; Lin, H.M.; Mar, B.G.; DeAngelo, D.J. Efficacy and safety of avapritinib in advanced systemic mastocytosis: interim analysis of the phase 2 PATHFINDER trial. Nat. Med., 2021, 27(12), 2192-2199.
[http://dx.doi.org/10.1038/s41591-021-01539-8] [PMID: 34873345]
[42]
DeAngelo, D.J.; Radia, D.H.; George, T.I.; Robinson, W.A.; Quiery, A.T.; Drummond, M.W.; Bose, P.; Hexner, E.O.; Winton, E.F.; Horny, H.P.; Tugnait, M.; Schmidt-Kittler, O.; Evans, E.K.; Lin, H.M.; Mar, B.G.; Verstovsek, S.; Deininger, M.W.; Gotlib, J. Safety and efficacy of avapritinib in advanced systemic mastocytosis: the phase 1 EXPLORER trial. Nat. Med., 2021, 27(12), 2183-2191.
[http://dx.doi.org/10.1038/s41591-021-01538-9] [PMID: 34873347]
[43]
Dummer, R.; Hauschild, A.; Santinami, M.; Atkinson, V.; Mandalà, M.; Kirkwood, J.M.; Chiarion Sileni, V.; Larkin, J.; Nyakas, M.; Dutriaux, C.; Haydon, A.; Robert, C.; Mortier, L.; Schachter, J.; Lesimple, T.; Plummer, R.; Dasgupta, K.; Gasal, E.; Tan, M.; Long, G.V.; Schadendorf, D. Five-year analysis of adjuvant dabrafenib plus trametinib in stage iii melanoma. N. Engl. J. Med., 2020, 383(12), 1139-1148.
[http://dx.doi.org/10.1056/NEJMoa2005493] [PMID: 32877599]
[44]
Robert, C.; Grob, J.J.; Stroyakovskiy, D.; Karaszewska, B.; Hauschild, A.; Levchenko, E.; Chiarion Sileni, V.; Schachter, J.; Garbe, C.; Bondarenko, I.; Gogas, H.; Mandalá, M.; Haanen, J.B.A.G.; Lebbé, C.; Mackiewicz, A.; Rutkowski, P.; Nathan, P.D.; Ribas, A.; Davies, M.A.; Flaherty, K.T.; Burgess, P.; Tan, M.; Gasal, E.; Voi, M.; Schadendorf, D.; Long, G.V. Five-year outcomes with dabrafenib plus trametinib in metastatic melanoma. N. Engl. J. Med., 2019, 381(7), 626-636.
[http://dx.doi.org/10.1056/NEJMoa1904059] [PMID: 31166680]
[45]
Crawford, K.; Bontrager, E.; Schwarz, M.A.; Chaturvedi, A.; Lee, D.D.; Md Sazzad, H.; von Holzen, U.; Zhang, C.; Schwarz, R.E.; Awasthi, N. Targeted FGFR/VEGFR/PDGFR inhibition with dovitinib enhances the effects of nab-paclitaxel in preclinical gastric cancer models. Cancer Biol. Ther., 2021, 22(10-12), 619-629.
[http://dx.doi.org/10.1080/15384047.2021.2011642] [PMID: 34882068]
[46]
Zhang, P.; Liu, X.; Abegg, D.; Tanaka, T.; Tong, Y.; Benhamou, R.I.; Baisden, J.; Crynen, G.; Meyer, S.M.; Cameron, M.D.; Chatterjee, A.K.; Adibekian, A.; Childs-Disney, J.L.; Disney, M.D. Reprogramming of protein-targeted small-molecule medicines to RNA by ribonuclease recruitment. J. Am. Chem. Soc., 2021, 143(33), 13044-13055.
[http://dx.doi.org/10.1021/jacs.1c02248] [PMID: 34387474]
[47]
Motzer, R.J.; Escudier, B.; McDermott, D.F.; George, S.; Hammers, H.J.; Srinivas, S.; Tykodi, S.S.; Sosman, J.A.; Procopio, G.; Plimack, E.R.; Castellano, D.; Choueiri, T.K.; Gurney, H.; Donskov, F.; Bono, P.; Wagstaff, J.; Gauler, T.C.; Ueda, T.; Tomita, Y.; Schutz, F.A.; Kollmannsberger, C.; Larkin, J.; Ravaud, A.; Simon, J.S.; Xu, L.A.; Waxman, I.M.; Sharma, P. Nivolumab versus everolimus in advanced renal-cell carcinoma. N. Engl. J. Med., 2015, 373(19), 1803-1813.
[http://dx.doi.org/10.1056/NEJMoa1510665] [PMID: 26406148]
[48]
Yao, J.C.; Fazio, N.; Singh, S.; Buzzoni, R.; Carnaghi, C.; Wolin, E.; Tomasek, J.; Raderer, M.; Lahner, H.; Voi, M.; Pacaud, L.B.; Rouyrre, N.; Sachs, C.; Valle, J.W.; Fave, G.D.; Van Cutsem, E.; Tesselaar, M.; Shimada, Y.; Oh, D.Y.; Strosberg, J.; Kulke, M.H.; Pavel, M.E. Everolimus for the treatment of advanced, non-functional neuroendocrine tumours of the lung or gastrointestinal tract (RADIANT-4): a randomised, placebo-controlled, phase 3 study. Lancet, 2016, 387(10022), 968-977.
[http://dx.doi.org/10.1016/S0140-6736(15)00817-X] [PMID: 26703889]
[49]
Li, Y.; Zhao, L.; Li, X.F. The hypoxia-activated prodrug th-302: Exploiting hypoxia in cancer therapy. Front. Pharmacol., 2021, 12, 636892.
[http://dx.doi.org/10.3389/fphar.2021.636892] [PMID: 33953675]
[50]
Brenner, A.J.; Floyd, J.; Fichtel, L.; Michalek, J.; Kanakia, K.P.; Huang, S.; Reardon, D.; Wen, P.Y.; Lee, E.Q. Phase 2 trial of hypoxia activated evofosfamide (TH302) for treatment of recurrent bevacizumab-refractory glioblastoma. Sci. Rep., 2021, 11(1), 2306.
[http://dx.doi.org/10.1038/s41598-021-81841-0] [PMID: 33504881]
[51]
Fröbom, R.; Berglund, E.; Berglund, D.; Nilsson, I.L.; Åhlén, J.; von Sivers, K.; Linder-Stragliotto, C.; Suenaert, P.; Karlsson-Parra, A.; Bränström, R. Phase I trial evaluating safety and efficacy of intratumorally administered inflammatory allogeneic dendritic cells (ilixadencel) in advanced gastrointestinal stromal tumors. Cancer Immunol. Immunother., 2020, 69(11), 2393-2401.
[http://dx.doi.org/10.1007/s00262-020-02625-5] [PMID: 32535637]
[52]
Karlsson-Parra, A.; Kovacka, J.; Heimann, E.; Jorvid, M.; Zeilemaker, S.; Longhurst, S.; Suenaert, P. Ilixadencel - an allogeneic cell-based anticancer immune primer for intratumoral administration. Pharm. Res., 2018, 35(8), 156.
[http://dx.doi.org/10.1007/s11095-018-2438-x] [PMID: 29904904]
[53]
Short, N.J.; Rytting, M.E.; Cortes, J.E. Acute myeloid leukaemia. Lancet, 2018, 392(10147), 593-606.
[http://dx.doi.org/10.1016/S0140-6736(18)31041-9] [PMID: 30078459]
[54]
Stone, R.M.; Mandrekar, S.J.; Sanford, B.L.; Laumann, K.; Geyer, S.; Bloomfield, C.D.; Thiede, C.; Prior, T.W.; Döhner, K.; Marcucci, G.; Lo-Coco, F.; Klisovic, R.B.; Wei, A.; Sierra, J.; Sanz, M.A.; Brandwein, J.M.; de Witte, T.; Niederwieser, D.; Appelbaum, F.R.; Medeiros, B.C.; Tallman, M.S.; Krauter, J.; Schlenk, R.F.; Ganser, A.; Serve, H.; Ehninger, G.; Amadori, S.; Larson, R.A.; Döhner, H. Midostaurin plus chemotherapy for acute myeloid leukemia with a flt3 mutation. N. Engl. J. Med., 2017, 377(5), 454-464.
[http://dx.doi.org/10.1056/NEJMoa1614359] [PMID: 28644114]
[55]
Tap, W.D.; Jones, R.L.; Van Tine, B.A.; Chmielowski, B.; Elias, A.D.; Adkins, D.; Agulnik, M.; Cooney, M.M.; Livingston, M.B.; Pennock, G.; Hameed, M.R.; Shah, G.D.; Qin, A.; Shahir, A.; Cronier, D.M.; Ilaria, R., Jr; Conti, I.; Cosaert, J.; Schwartz, G.K. Olaratumab and doxorubicin versus doxorubicin alone for treatment of soft-tissue sarcoma: An open-label phase 1b and randomised phase 2 trial. Lancet, 2016, 388(10043), 488-497.
[http://dx.doi.org/10.1016/S0140-6736(16)30587-6] [PMID: 27291997]
[56]
Tap, W.D.; Wagner, A.J.; Schöffski, P.; Martin-Broto, J.; Krarup-Hansen, A.; Ganjoo, K.N.; Yen, C.C.; Abdul Razak, A.R.; Spira, A.; Kawai, A.; Le Cesne, A.; Van Tine, B.A.; Naito, Y.; Park, S.H.; Fedenko, A.; Pápai, Z.; Soldatenkova, V.; Shahir, A.; Mo, G.; Wright, J.; Jones, R.L. Effect of doxorubicin plus olaratumab vs doxorubicin plus placebo on survival in patients with advanced soft tissue sarcomas: The announce randomized clinical trial. JAMA, 2020, 323(13), 1266-1276.
[http://dx.doi.org/10.1001/jama.2020.1707] [PMID: 32259228]
[57]
Woodhead, A.J.; Angove, H.; Carr, M.G.; Chessari, G.; Congreve, M.; Coyle, J.E.; Cosme, J.; Graham, B.; Day, P.J.; Downham, R.; Fazal, L.; Feltell, R.; Figueroa, E.; Frederickson, M.; Lewis, J.; McMenamin, R.; Murray, C.W.; O’Brien, M.A.; Parra, L.; Patel, S.; Phillips, T.; Rees, D.C.; Rich, S.; Smith, D.M.; Trewartha, G.; Vinkovic, M.; Williams, B.; Woolford, A.J.A. Discovery of (2,4-dihydroxy-5-isopropylphenyl)-[5-(4-methylpiperazin-1-ylmethyl)-1,3-dihydroisoindol-2-yl]methanone (AT13387), a novel inhibitor of the molecular chaperone Hsp90 by fragment based drug design. J. Med. Chem., 2010, 53(16), 5956-5969.
[http://dx.doi.org/10.1021/jm100060b] [PMID: 20662534]
[58]
Spiegelberg, D.; Abramenkovs, A.; Mortensen, A.C.L.; Lundsten, S.; Nestor, M.; Stenerlöw, B. The HSP90 inhibitor Onalespib exerts synergistic anti-cancer effects when combined with radiotherapy: An in vitro and in vivo approach. Sci. Rep., 2020, 10(1), 5923.
[http://dx.doi.org/10.1038/s41598-020-62293-4] [PMID: 32246062]
[59]
Rosenbaum, E.; Kelly, C.; D’Angelo, S.P.; Dickson, M.A.; Gounder, M.; Keohan, M.L.; Movva, S.; Condy, M.; Adamson, T.; Mcfadyen, C.R.; Antonescu, C.R.; Hwang, S.; Singer, S.; Qin, L.X.; Tap, W.D.; Chi, P. A phase i study of binimetinib (mek162) combined with pexidartinib (plx3397) in patients with advanced gastrointestinal stromal tumor. Oncologist, 2019, 24(10), 1309-e983.
[http://dx.doi.org/10.1634/theoncologist.2019-0418] [PMID: 31213500]
[60]
Lamb, Y.N. Pexidartinib: First Approval. Drugs, 2019, 79(16), 1805-1812.
[http://dx.doi.org/10.1007/s40265-019-01210-0] [PMID: 31602563]
[61]
Cortes, J.E.; Kim, D.W.; Pinilla-Ibarz, J.; le Coutre, P.; Paquette, R.; Chuah, C.; Nicolini, F.E.; Apperley, J.F.; Khoury, H.J.; Talpaz, M.; DiPersio, J.; DeAngelo, D.J.; Abruzzese, E.; Rea, D.; Baccarani, M.; Müller, M.C.; Gambacorti-Passerini, C.; Wong, S.; Lustgarten, S.; Rivera, V.M.; Clackson, T.; Turner, C.D.; Haluska, F.G.; Guilhot, F.; Deininger, M.W.; Hochhaus, A.; Hughes, T.; Goldman, J.M.; Shah, N.P.; Kantarjian, H. A phase 2 trial of ponatinib in Philadelphia chromosome-positive leukemias. N. Engl. J. Med., 2013, 369(19), 1783-1796.
[http://dx.doi.org/10.1056/NEJMoa1306494] [PMID: 24180494]
[62]
Trametinib, Z.R. Recent Results Cancer Res., 2014, 201, 241-248.
[http://dx.doi.org/10.1007/978-3-642-54490-3_15] [PMID: 24756797]
[63]
Gounder, M.M.; Solit, D.B.; Tap, W.D. Trametinib in histiocytic sarcoma with an activating map2k1 (mek1) mutation. N. Engl. J. Med., 2018, 378(20), 1945-1947.
[http://dx.doi.org/10.1056/NEJMc1511490] [PMID: 29768143]

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