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.
[http://dx.doi.org/10.1038/s41572-021-00254-5] [PMID: 33737510]
[http://dx.doi.org/10.1158/1078-0432.CCR-20-1706] [PMID: 32601076]
[http://dx.doi.org/10.2174/1568009619666190326123945] [PMID: 30914028]
[http://dx.doi.org/10.1038/s41571-022-00606-4] [PMID: 35217782]
[http://dx.doi.org/10.1093/annonc/mdy095] [PMID: 29846513]
[http://dx.doi.org/10.1097/CCO.0000000000000549] [PMID: 31033566]
[PMID: 8548747]
[http://dx.doi.org/10.1038/nm0596-561] [PMID: 8616716]
[http://dx.doi.org/10.1007/s00280-013-2135-8] [PMID: 23503753]
[http://dx.doi.org/10.1182/bloodadvances.2019001329] [PMID: 32559295]
[http://dx.doi.org/10.1007/s00280-006-0376-5] [PMID: 17136543]
[http://dx.doi.org/10.1111/j.1349-7006.2006.00263.x] [PMID: 16916320]
[http://dx.doi.org/10.1182/blood-2002-07-2307] [PMID: 12531805]
[http://dx.doi.org/10.1056/NEJMoa1816714] [PMID: 30779529]
[http://dx.doi.org/10.2217/fon-2019-0633] [PMID: 31755321]
[http://dx.doi.org/10.1002/ijc.25864] [PMID: 21170960]
[http://dx.doi.org/10.1517/13543784.2012.684752] [PMID: 22577890]
[http://dx.doi.org/10.1038/s41416-019-0498-2] [PMID: 31235865]
[http://dx.doi.org/10.1200/JCO.21.00217] [PMID: 34343033]
[http://dx.doi.org/10.1016/j.ccell.2019.04.006] [PMID: 31085175]
[http://dx.doi.org/10.1158/2159-8290.CD-NB2016-165] [PMID: 28077435]
[http://dx.doi.org/10.1177/1758835920986498] [PMID: 33473249]
[http://dx.doi.org/10.1080/23723556.2018.1435183] [PMID: 30250891]
[http://dx.doi.org/10.1016/j.ctrv.2020.102017] [PMID: 32335505]
[http://dx.doi.org/10.1038/nrd1381] [PMID: 15136787]
[http://dx.doi.org/10.1016/j.ccell.2021.07.005] [PMID: 34388377]
[http://dx.doi.org/10.1158/1078-0432.CCR-12-0625] [PMID: 22745105]
[http://dx.doi.org/10.1097/CCO.0000000000000642] [PMID: 32541319]
[http://dx.doi.org/10.3892/ol.2016.4909] [PMID: 27602110]
[http://dx.doi.org/10.1186/s40880-017-0263-y] [PMID: 29273089]
[http://dx.doi.org/10.1007/978-3-642-54490-3_3] [PMID: 24756785]
[http://dx.doi.org/10.2165/00003495-200868040-00005] [PMID: 18318563]
[http://dx.doi.org/10.2174/1871520621666210402110331] [PMID: 33797387]
[http://dx.doi.org/10.1038/nrclinonc.2016.139] [PMID: 27752053]
[http://dx.doi.org/10.1158/1535-7163.MCT-14-0219] [PMID: 25416789]
[http://dx.doi.org/10.3390/ijms22094875] [PMID: 34062977]
[http://dx.doi.org/10.1186/s13045-018-0664-7] [PMID: 30231931]
[http://dx.doi.org/10.3892/ol.2020.11685] [PMID: 32724339]
[http://dx.doi.org/10.1038/nrclinonc.2016.53] [PMID: 27071350]
[http://dx.doi.org/10.1158/1078-0432.CCR-20-4691] [PMID: 33766817]
[http://dx.doi.org/10.1038/s41591-021-01539-8] [PMID: 34873345]
[http://dx.doi.org/10.1038/s41591-021-01538-9] [PMID: 34873347]
[http://dx.doi.org/10.1056/NEJMoa2005493] [PMID: 32877599]
[http://dx.doi.org/10.1056/NEJMoa1904059] [PMID: 31166680]
[http://dx.doi.org/10.1080/15384047.2021.2011642] [PMID: 34882068]
[http://dx.doi.org/10.1021/jacs.1c02248] [PMID: 34387474]
[http://dx.doi.org/10.1056/NEJMoa1510665] [PMID: 26406148]
[http://dx.doi.org/10.1016/S0140-6736(15)00817-X] [PMID: 26703889]
[http://dx.doi.org/10.3389/fphar.2021.636892] [PMID: 33953675]
[http://dx.doi.org/10.1038/s41598-021-81841-0] [PMID: 33504881]
[http://dx.doi.org/10.1007/s00262-020-02625-5] [PMID: 32535637]
[http://dx.doi.org/10.1007/s11095-018-2438-x] [PMID: 29904904]
[http://dx.doi.org/10.1016/S0140-6736(18)31041-9] [PMID: 30078459]
[http://dx.doi.org/10.1056/NEJMoa1614359] [PMID: 28644114]
[http://dx.doi.org/10.1016/S0140-6736(16)30587-6] [PMID: 27291997]
[http://dx.doi.org/10.1001/jama.2020.1707] [PMID: 32259228]
[http://dx.doi.org/10.1021/jm100060b] [PMID: 20662534]
[http://dx.doi.org/10.1038/s41598-020-62293-4] [PMID: 32246062]
[http://dx.doi.org/10.1634/theoncologist.2019-0418] [PMID: 31213500]
[http://dx.doi.org/10.1007/s40265-019-01210-0] [PMID: 31602563]
[http://dx.doi.org/10.1056/NEJMoa1306494] [PMID: 24180494]
[http://dx.doi.org/10.1007/978-3-642-54490-3_15] [PMID: 24756797]
[http://dx.doi.org/10.1056/NEJMc1511490] [PMID: 29768143]