Literature DB >> 33574423

Clinical data mining reveals analgesic effects of lapatinib in cancer patients.

Shuo Zhou1,2, Fang Zheng3,4, Chang-Guo Zhan5,6.   

Abstract

Microsomal prostaglandin E2 synthase 1 (mPGES-1) is recognized as a promising target for a next generation of anti-inflammatory drugs that are not expected to have the side effects of currently available anti-inflammatory drugs. Lapatinib, an FDA-approved drug for cancer treatment, has recently been identified as an mPGES-1 inhibitor. But the efficacy of lapatinib as an analgesic remains to be evaluated. In the present clinical data mining (CDM) study, we have collected and analyzed all lapatinib-related clinical data retrieved from clinicaltrials.gov. Our CDM utilized a meta-analysis protocol, but the clinical data analyzed were not limited to the primary and secondary outcomes of clinical trials, unlike conventional meta-analyses. All the pain-related data were used to determine the numbers and odd ratios (ORs) of various forms of pain in cancer patients with lapatinib treatment. The ORs, 95% confidence intervals, and P values for the differences in pain were calculated and the heterogeneous data across the trials were evaluated. For all forms of pain analyzed, the patients received lapatinib treatment have a reduced occurrence (OR 0.79; CI 0.70-0.89; P = 0.0002 for the overall effect). According to our CDM results, available clinical data for 12,765 patients enrolled in 20 randomized clinical trials indicate that lapatinib therapy is associated with a significant reduction in various forms of pain, including musculoskeletal pain, bone pain, headache, arthralgia, and pain in extremity, in cancer patients. Our CDM results have demonstrated the significant analgesic effects of lapatinib, suggesting that lapatinib may be repurposed as a novel type of analgesic.

Entities:  

Year:  2021        PMID: 33574423     DOI: 10.1038/s41598-021-82318-w

Source DB:  PubMed          Journal:  Sci Rep        ISSN: 2045-2322            Impact factor:   4.379


  29 in total

1.  Aminothiazole-featured pirinixic acid derivatives as dual 5-lipoxygenase and microsomal prostaglandin E2 synthase-1 inhibitors with improved potency and efficiency in vivo.

Authors:  Thomas Hanke; Friederike Dehm; Stefanie Liening; Sven-Desiderius Popella; Jonas Maczewsky; Max Pillong; Jens Kunze; Christina Weinigel; Dagmar Barz; Astrid Kaiser; Mario Wurglics; Michael Lämmerhofer; Gisbert Schneider; Lidia Sautebin; Manfred Schubert-Zsilavecz; Oliver Werz
Journal:  J Med Chem       Date:  2013-11-15       Impact factor: 7.446

2.  Safety of Nonsteroidal Antiinflammatory Drugs.

Authors:  David T Felson
Journal:  N Engl J Med       Date:  2016-12-29       Impact factor: 91.245

3.  7-Phenyl-imidazoquinolin-4(5H)-one derivatives as selective and orally available mPGES-1 inhibitors.

Authors:  Tomoya Shiro; Keisuke Kakiguchi; Hirotada Takahashi; Hidetaka Nagata; Masanori Tobe
Journal:  Bioorg Med Chem       Date:  2013-04-06       Impact factor: 3.641

4.  Structural Insights for the Optimization of Dihydropyrimidin-2(1H)-one Based mPGES-1 Inhibitors.

Authors:  Stefania Terracciano; Gianluigi Lauro; Maria Strocchia; Katrin Fischer; Oliver Werz; Raffaele Riccio; Ines Bruno; Giuseppe Bifulco
Journal:  ACS Med Chem Lett       Date:  2015-01-07       Impact factor: 4.345

5.  Discovery and biological evaluation of a novel class of dual microsomal prostaglandin E2 synthase-1/5-lipoxygenase inhibitors based on 2-[(4,6-diphenethoxypyrimidin-2-yl)thio]hexanoic acid.

Authors:  Martina Hieke; Christine Greiner; Michaela Dittrich; Felix Reisen; Gisbert Schneider; Manfred Schubert-Zsilavecz; Oliver Werz
Journal:  J Med Chem       Date:  2011-06-08       Impact factor: 7.446

6.  Impaired inflammatory and pain responses in mice lacking an inducible prostaglandin E synthase.

Authors:  Catherine E Trebino; Jeffrey L Stock; Colleen P Gibbons; Brian M Naiman; Timothy S Wachtmann; John P Umland; Karamjeet Pandher; Jean-Martin Lapointe; Sipra Saha; Marsha L Roach; Demetrius Carter; Nathalie A Thomas; Becky A Durtschi; John D McNeish; John E Hambor; Per-Johan Jakobsson; Thomas J Carty; Jose R Perez; Laurent P Audoly
Journal:  Proc Natl Acad Sci U S A       Date:  2003-06-30       Impact factor: 11.205

7.  Discovery and Characterization of 2-Acylaminoimidazole Microsomal Prostaglandin E Synthase-1 Inhibitors.

Authors:  Matthew A Schiffler; Stephen Antonysamy; Shobha N Bhattachar; Kristina M Campanale; Srinivasan Chandrasekhar; Bradley Condon; Prashant V Desai; Matthew J Fisher; Christopher Groshong; Anita Harvey; Michael J Hickey; Norman E Hughes; Scott A Jones; Euibong J Kim; Steven L Kuklish; John G Luz; Bryan H Norman; Richard E Rathmell; John R Rizzo; Thomas W Seng; Stefan J Thibodeaux; Timothy A Woods; Jeremy S York; Xiao-Peng Yu
Journal:  J Med Chem       Date:  2015-12-18       Impact factor: 7.446

8.  Microsomal prostaglandin E synthase-1 is the central switch during immune-induced pyresis.

Authors:  David Engblom; Sipra Saha; Linda Engström; Marie Westman; Laurent P Audoly; Per-Johan Jakobsson; Anders Blomqvist
Journal:  Nat Neurosci       Date:  2003-10-19       Impact factor: 24.884

9.  Synthesis and biological evaluation of substituted imidazoquinoline derivatives as mPGES-1 inhibitors.

Authors:  Tomoya Shiro; Keisuke Kakiguchi; Hirotada Takahashi; Hidetaka Nagata; Masanori Tobe
Journal:  Bioorg Med Chem       Date:  2013-01-16       Impact factor: 3.641

10.  Cardiovascular Safety of Celecoxib, Naproxen, or Ibuprofen for Arthritis.

Authors:  Steven E Nissen; Neville D Yeomans; Daniel H Solomon; Thomas F Lüscher; Peter Libby; M Elaine Husni; David Y Graham; Jeffrey S Borer; Lisa M Wisniewski; Katherine E Wolski; Qiuqing Wang; Venu Menon; Frank Ruschitzka; Michael Gaffney; Bruce Beckerman; Manuela F Berger; Weihang Bao; A Michael Lincoff
Journal:  N Engl J Med       Date:  2016-11-13       Impact factor: 91.245

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