MAP kinase signaling and inhibition in melanoma

被引:114
|
作者
Sullivan, R. J. [1 ]
Flaherty, K. [1 ]
机构
[1] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA
关键词
melanoma; targeted therapy; BRAF; RANDOMIZED DISCONTINUATION TRIAL; CHRONIC MYELOID-LEUKEMIA; B-RAF INHIBITOR; NF-KAPPA-B; BRAF INHIBITION; WILD-TYPE; MULTIKINASE INHIBITOR; ACQUIRED-RESISTANCE; AZD6244; ARRY-142886; IMPROVED SURVIVAL;
D O I
10.1038/onc.2012.345
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The mitogen-activated protein kinase (MAPK) pathway is critical to oncogenic signaling in the majority of patients with malignant melanoma. Driver mutations in both NRAS and BRAF have important implications for prognosis and treatment. The development of inhibitors to mediators of the MAPK pathway, including those to CRAF, BRAF, and MEK, has led to major advances in the treatment of patients with melanoma. In particular, the selective BRAF inhibitor vemurafenib has been shown to improve overall survival in patients with tumors harboring BRAF mutations. However, the duration of benefit is limited in many patients and highlights the need for understanding the limitations of therapy in order to devise more effective strategies. MEK inhibitors have proven to particularly active in BRAF mutant melanomas also. Emerging knowledge about mechanisms of resistance as well as a more complete understanding of the biology of MAPK pathway signaling provides insight into rational combination regimens and sequences of molecularly targeted therapies.
引用
收藏
页码:2373 / 2379
页数:7
相关论文
共 50 条
  • [41] Attenuation of pattern recognition receptor signaling is mediated by a MAP kinase kinase kinase
    Mithoe, Sharon C.
    Ludwig, Christina
    Pel, Michiel J. C.
    Cucinotta, Mara
    Casartelli, Alberto
    Mbengue, Malick
    Sklenar, Jan
    Derbyshire, Paul
    Robatzek, Silke
    Pieterse, Corne M. J.
    Aebersold, Ruedi
    Menke, Frank L. H.
    EMBO REPORTS, 2016, 17 (03) : 441 - 454
  • [42] Modulation of MAP kinase signaling pathways in CD133-positive melanoma cells overcomes their resistance to apoptosis
    Hassan, M.
    Feyen, O.
    Mirmohammadsadegh, A.
    Gulbins, E.
    Hengge, U.
    EXPERIMENTAL DERMATOLOGY, 2009, 18 (03) : 317 - 317
  • [43] Uveitis as a Result of MAP Kinase Pathway Inhibition
    Joshi, Lavnish
    Karydis, Andreas
    Gemenetzi, Maria
    Shao, Emily H.
    Taylor, Simon R. J.
    CASE REPORTS IN OPHTHALMOLOGY, 2013, 4 (03): : 279 - 282
  • [44] INHIBITION OF THE EGF-ACTIVATED MAP KINASE SIGNALING PATHWAY BY ADENOSINE-3',5'-MONOPHOSPHATE
    WU, J
    DENT, P
    JELINEK, T
    WOLFMAN, A
    WEBER, MJ
    STURGILL, TW
    SCIENCE, 1993, 262 (5136) : 1065 - 1069
  • [45] Inhibition of protein phosphatase methylesterase 1 dysregulates MAP kinase signaling and attenuates muscle cell differentiation
    Labuzan, Sydney A.
    Lynch, Sarah A.
    Cooper, Lisa M.
    Waddell, David S.
    GENE, 2020, 739
  • [46] MAP KINASE KINASE KINASE, MAP KINASE KINASE AND MAP KINASE
    MARSHALL, CJ
    CURRENT OPINION IN GENETICS & DEVELOPMENT, 1994, 4 (01) : 82 - 89
  • [47] Pharmacological inhibition of Rho-kinase signaling with Y-27632 blocks melanoma tumor growth
    Routhier, Alissa
    Astuccio, Michelle
    Lahey, Deanna
    Monfredo, Nicholas
    Johnson, Alyssa
    Callahan, William
    Partington, Amy
    Fellows, Kelly
    Ouellette, Lori
    Zhidro, Sofiela
    Goodrow, Carrie
    Smith, Alexis
    Sullivan, Kaitlyn
    Simone, Peter
    Le, Leo
    Vezuli, Bora
    Zohni, Micheline
    West, Elizabeth
    Gleason, Daniel
    Bryan, Brad
    ONCOLOGY REPORTS, 2010, 23 (03) : 861 - 867
  • [48] Modulation of the MAP kinase signaling cascade by Raf kinase inhibitory protein
    Trakul, N
    Rosner, MR
    CELL RESEARCH, 2005, 15 (01) : 19 - 23
  • [49] Modulation of the MAP kinase signaling cascade by Raf kinase inhibitory protein
    Nicholas TRAKUL
    Marsha R. ROSNER
    Cell Research, 2005, (01) : 19 - 23
  • [50] Modulation of the MAP kinase signaling cascade by Raf kinase inhibitory protein
    Nicholas TRAKUL
    Marsha R ROSNER
    Cell Research, 2005, 15 : 19 - 23