MEK inhibitors-novel targeted therapies of neurofibromatosis associated benign and malignant lesions

被引：25
作者：
Harder, Anja [1 ,2 ,3 ]
机构：
[1] Martin Luther Univ Halle Wittenberg, Inst Pathol, Magdeburger Str 14, D-06120 Halle, Saale, Germany
[2] Univ Hosp Munster, Inst Neuropathol, Munster, Germany
[3] Brandenburg Med Sch Theodor Fontane & Univ Potsda, Fac Hlth Sci, Joint Fac Brandenburg Univ Technol Cottbus Senfte, Potsdam, Germany
来源：
BIOMARKER RESEARCH | 2021年 / 9卷 / 01期
关键词：
MEK inhibitor; Neurofibromatosis; NF1; NF2; Schwannomatosis; LGG; Neurofibroma; MPNST; Glioblastoma; RASopathy;
D O I：
10.1186/s40364-021-00281-0
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
MAP/ERK kinase 1 and 2 (MEK 1/2) inhibitors (MEKi) are investigated in several trials to treat lesions that arise from pathogenic variants of the Neurofibromatosis type 1 and type 2 genes (NF1, NF2). These trials showed that MEKi are capable to shrink volume of low grade gliomas and plexiform neurofibromas in NF1. Targeting other lesions being associated with a high morbidity in NF1 seems to be promising. Due to involvement of multiple pathways in NF2 associated lesions as well as in malignant tumors, MEKi are also used in combination therapies. This review outlines the current state of MEKi application in neurofibromatosis and associated benign and malignant lesions.
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页数：9
相关论文
共 81 条
[1]   Structural fingerprints of the Ras-GTPase activating proteins neurofibromin and p120GAP [J].
Ahmadian, MR ;
Kiel, C ;
Stege, P ;
Scheffzek, K .
JOURNAL OF MOLECULAR BIOLOGY, 2003, 329 (04) :699-710
[2]   Combinatorial therapeutic targeting of BMP2 and MEK-ERK pathways in NF1-associated malignant peripheral nerve sheath tumors [J].
Ahsan, Sidra ;
Ge, Yubin ;
Tainsky, Michael A. .
ONCOTARGET, 2016, 7 (35) :57171-57185
[3]   Prolonged disease control with MEK inhibitor in neurofibromatosis type I-associated glioblastoma [J].
Ameratunga, M. ;
McArthur, G. ;
Gan, H. ;
Cher, L. .
JOURNAL OF CLINICAL PHARMACY AND THERAPEUTICS, 2016, 41 (03) :357-359
[4]   Durable Complete Response of a Recurrent Mesencephalic Glioblastoma Treated with Trametinib and Low-Dose Dabrafenib in a Patient with Neurofibromatosis Type 1 [J].
Awada, Gil ;
Serruys, Daphne ;
Schwarze, Julia Katharina ;
Van de Voorde, Lien ;
Duerinck, Johnny ;
Neyns, Bart .
CASE REPORTS IN ONCOLOGY, 2020, 13 (02) :1031-1036
[5]   A phase I trial of the MEK inhibitor selumetinib (AZD6244) in pediatric patients with recurrent or refractory low-grade glioma: a Pediatric Brain Tumor Consortium (PBTC) study [J].
Banerjee, Anuradha ;
Jakacki, Regina I. ;
Onar-Thomas, Arzu ;
Wu, Shengjie ;
Nicolaides, Theodore ;
Poussaint, Tina Young ;
Fangusaro, Jason ;
Phillips, Joanna ;
Perry, Arie ;
Turner, David ;
Prados, Michael ;
Packer, Roger J. ;
Qaddoumi, Ibrahim ;
Gururangan, Sridharan ;
Pollack, Ian F. ;
Goldman, Stewart ;
Doyle, Lawrence A. ;
Stewart, Clinton F. ;
Boyett, James M. ;
Kun, Larry E. ;
Fouladi, Maryam .
NEURO-ONCOLOGY, 2017, 19 (08) :1135-1144
[6]   Therapeutic advances for the tumors associated with neurofibromatosis type 1, type 2, and schwannomatosis [J].
Blakeley, Jaishri O. ;
Plotkin, Scott R. .
NEURO-ONCOLOGY, 2016, 18 (05) :624-638
[7]  
Blakeley Jaishri O, 2012, Am J Med Genet A, V158A, P24, DOI 10.1002/ajmg.a.34359
[8]   Modulation of spine fusion with BMP-2, MEK inhibitor (PD0325901) and zoledronic acid in a murine model of NF1 double inactivation [J].
Bobyn, Justin D. ;
Deo, Nikita ;
Little, David G. ;
Schindeler, Aaron .
JOURNAL OF ORTHOPAEDIC SCIENCE, 2021, 26 (04) :684-689
[9]   Selumetinib for children with plexiform neurofi bromas [J].
Burki, Talha Khan .
LANCET ONCOLOGY, 2017, 18 (02) :E69-E69
[10]   Prognosis and risk factors for malignant peripheral nerve sheath tumor: a systematic review and meta-analysis [J].
Cai, Zhenyu ;
Tang, Xiaodong ;
Liang, Haijie ;
Yang, Rongli ;
Yan, Taiqiang ;
Guo, Wei .
WORLD JOURNAL OF SURGICAL ONCOLOGY, 2020, 18 (01)
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