Literature DB >> 35171389

Selumetinib: a selective MEK1 inhibitor for solid tumor treatment.

Mohaddeseh Hedayat1, Reza Jafari2,3, Naime Majidi Zolbanin4,5.   

Abstract

Cancer incidence is rapidly growing. Solid tumors are responsible for a majority of cancers. Recently, molecular-targeted agents have played a significant role in cancer treatment. Ras-Raf-MEK-ERK signaling pathway, is a substantial element in the survival, propagation, and drug resistance of human cancers. MEK is a specific part of the so-called cascade, and ERK proteins are its sole target. Furthermore, their downstream position in the Ras-ERK cascade, is noteworthy to direct their function in patients with upstream mutated genes. MEK1 mutations are responsible for initiating several solid tumors. Selumetinib (AZD6244) is a second-generation, selective, potent, and non-ATP competitive allosteric MEK1 inhibitor. The efficacy of selumetinib in various solid tumors such as colorectal cancer, lung cancer, neurofibroma, and melanoma is investigated. The present paper provides an overview of the MAPK cascade, the role of selumetinib as a MEK1/2 inhibitor, and the related findings of clinical trials for solid tumor treatment.
© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.

Entities:  

Keywords:  Cancer; MAPK; MEKIs; Selumetinib; Solid tumors

Year:  2022        PMID: 35171389     DOI: 10.1007/s10238-021-00783-z

Source DB:  PubMed          Journal:  Clin Exp Med        ISSN: 1591-8890            Impact factor:   3.984


  65 in total

1.  Selumetinib in Combination With Dacarbazine in Patients With Metastatic Uveal Melanoma: A Phase III, Multicenter, Randomized Trial (SUMIT).

Authors:  Richard D Carvajal; Sophie Piperno-Neumann; Ellen Kapiteijn; Paul B Chapman; Stephen Frank; Anthony M Joshua; Josep M Piulats; Pascal Wolter; Veronique Cocquyt; Bartosz Chmielowski; T R Jeffry Evans; Lauris Gastaud; Gerald Linette; Carola Berking; Jacob Schachter; Manuel J Rodrigues; Alexander N Shoushtari; Delyth Clemett; Dana Ghiorghiu; Gabriella Mariani; Shirley Spratt; Susan Lovick; Peter Barker; Elaine Kilgour; Zhongwu Lai; Gary K Schwartz; Paul Nathan
Journal:  J Clin Oncol       Date:  2018-03-12       Impact factor: 44.544

2.  Clinical responses to selumetinib (AZD6244; ARRY-142886)-based combination therapy stratified by gene mutations in patients with metastatic melanoma.

Authors:  Sapna P Patel; Alexander J Lazar; Nicholas E Papadopoulos; Ping Liu; Jeffrey R Infante; Michelle R Glass; Carol S Vaughn; Patricia M LoRusso; Roger B Cohen; Michael A Davies; Kevin B Kim
Journal:  Cancer       Date:  2012-09-12       Impact factor: 6.860

3.  A phase II evaluation of selumetinib (AZD6244, ARRY-142886), a selective MEK-1/2 inhibitor in the treatment of recurrent or persistent endometrial cancer: an NRG Oncology/Gynecologic Oncology Group study.

Authors:  Robert L Coleman; Michael W Sill; Premal H Thaker; David P Bender; Daron Street; William P McGuire; Carolyn M Johnston; Jacob Rotmensch
Journal:  Gynecol Oncol       Date:  2015-04-14       Impact factor: 5.482

Review 4.  Global trends in the distribution of cancer types among patients in oncology phase I trials, 1991-2015.

Authors:  Kota Itahashi; Toshio Shimizu; Takafumi Koyama; Shunsuke Kondo; Yutaka Fujiwara; Noboru Yamamoto
Journal:  Invest New Drugs       Date:  2018-08-07       Impact factor: 3.850

5.  A phase I study of selumetinib (AZD6244/ARRY-142866), a MEK1/2 inhibitor, in combination with cetuximab in refractory solid tumors and KRAS mutant colorectal cancer.

Authors:  Dustin A Deming; Ludmila L Cavalcante; Sam J Lubner; Daniel L Mulkerin; Noelle K LoConte; Jens C Eickhoff; Jill M Kolesar; Suzanne Fioravanti; Tim F Greten; Kathryn Compton; Austin G Doyle; George Wilding; Austin Duffy; Glenn Liu
Journal:  Invest New Drugs       Date:  2015-12-14       Impact factor: 3.850

6.  Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.

Authors:  Freddie Bray; Jacques Ferlay; Isabelle Soerjomataram; Rebecca L Siegel; Lindsey A Torre; Ahmedin Jemal
Journal:  CA Cancer J Clin       Date:  2018-09-12       Impact factor: 508.702

7.  A randomised phase II trial of selumetinib vs selumetinib plus temsirolimus for soft-tissue sarcomas.

Authors:  Z Eroglu; H A Tawbi; J Hu; M Guan; P H Frankel; N H Ruel; S Wilczynski; S Christensen; D R Gandara; W A Chow
Journal:  Br J Cancer       Date:  2015-04-21       Impact factor: 7.640

8.  A phase I trial of vertical inhibition of IGF signalling using cixutumumab, an anti-IGF-1R antibody, and selumetinib, an MEK 1/2 inhibitor, in advanced solid tumours.

Authors:  B A Wilky; M A Rudek; S Ahmed; D A Laheru; D Cosgrove; R C Donehower; B Nelkin; D Ball; L A Doyle; H Chen; X Ye; G Bigley; C Womack; N S Azad
Journal:  Br J Cancer       Date:  2014-09-30       Impact factor: 7.640

9.  Safety and tolerability of selumetinib as a monotherapy, or in combination with docetaxel as second-line therapy, in Japanese patients with advanced solid malignancies or non-small cell lung cancer.

Authors:  Takashi Seto; Fumihiko Hirai; Hideo Saka; Yoshihito Kogure; Kiyotaka Yoh; Seiji Niho; Kenjiro Fukase; Hitoshi Shimada; Michitaka Sasai; Koichi Fukino
Journal:  Jpn J Clin Oncol       Date:  2018-01-01       Impact factor: 3.019

10.  The role of SOX2 overexpression in prognosis of patients with solid tumors: A meta-analysis and system review.

Authors:  Shengjie Wang; Xinli Liu; Ying Chen; Xiaozhen Zhan; Tujin Wu; Bing Chen; Guangwen Sun; Songling Yan; Lin Xu
Journal:  Medicine (Baltimore)       Date:  2020-03       Impact factor: 1.817

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