Targeting RTK Signaling Pathways in Cancer

被引:299
作者
Regad, Tarik [1 ]
机构
[1] Nottingham Trent Univ, John Van Geest Canc Res Ctr, Sch Sci & Technol, Clifton Lane, Nottingham NG11 8NS, England
关键词
RTK; MAP kinase; PI3K; AKT; small molecule inhibitors; cancer; GROWTH-FACTOR-RECEPTOR; SQUAMOUS-CELL CARCINOMA; COMPARATIVE GENOMIC HYBRIDIZATION; GASTROINTESTINAL STROMAL TUMORS; METASTATIC BREAST-CANCER; TYROSINE KINASE DOMAIN; AFATINIB BIBW 2992; C-MET; LUNG-CANCER; PROTEIN-KINASE;
D O I
10.3390/cancers7030860
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The RAS/MAP kinase and the RAS/PI3K/AKT pathways play a key role in the regulation of proliferation, differentiation and survival. The induction of these pathways depends on Receptor Tyrosine Kinases (RTKs) that are activated upon ligand binding. In cancer, constitutive and aberrant activations of components of those pathways result in increased proliferation, survival and metastasis. For instance, mutations affecting RTKs, Ras, B-Raf, PI3K and AKT are common in perpetuating the malignancy of several types of cancers and from different tissue origins. Therefore, these signaling pathways became prime targets for cancer therapy. This review aims to provide an overview about the most frequently encountered mutations, the pathogenesis that results from such mutations and the known therapeutic strategies developed to counteract their aberrant functions.
引用
收藏
页码:1758 / 1784
页数:27
相关论文
共 182 条
[1]   Sunitinib malate for the treatment of metastatic renal cell carcinoma and gastrointestinal stromal tumors [J].
Adams, Val R. ;
Leggas, Markos .
CLINICAL THERAPEUTICS, 2007, 29 (07) :1338-1353
[2]   Akt inhibitor MK-2206 promotes anti-tumor activity and cell death by modulation of AIF and Ezrin in colorectal cancer [J].
Agarwal, Ekta ;
Chaudhuri, Anathbandhu ;
Leiphrakpam, Premila D. ;
Haferbier, Katie L. ;
Brattain, Michael G. ;
Chowdhury, Sanjib .
BMC CANCER, 2014, 14
[3]   Mechanisms of FGFR-mediated carcinogenesis [J].
Ahmad, Imran ;
Iwata, Tomoko ;
Leung, Hing Y. .
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH, 2012, 1823 (04) :850-860
[4]   Characterization of a 3-phosphoinositide-dependent protein kinase which phosphorylates and activates protein kinase B alpha [J].
Alessi, DR ;
James, SR ;
Downes, CP ;
Holmes, AB ;
Gaffney, PRJ ;
Reese, CB ;
Cohen, P .
CURRENT BIOLOGY, 1997, 7 (04) :261-269
[5]  
[Anonymous], COLD SPRING HARB PER
[6]   Detection of amplified oncogenes by genome DNA microarrays in human primary esophageal squamous cell carcinoma: comparison with conventional comparative genomic hybridization analysis [J].
Arai, H ;
Ueno, T ;
Tangoku, A ;
Yoshino, S ;
Abe, T ;
Kawauchi, S ;
Oga, A ;
Furuya, T ;
Oka, M ;
Sasaki, K .
CANCER GENETICS AND CYTOGENETICS, 2003, 146 (01) :16-21
[7]   Therapeutic targeting of c-KIT in cancer [J].
Ashman, Leonie K. ;
Griffith, Renate .
EXPERT OPINION ON INVESTIGATIONAL DRUGS, 2013, 22 (01) :103-115
[8]  
Bagai R, 2010, IDRUGS, V13, P404
[9]   MOLECULAR ALTERATIONS OF THE AKT2 ONCOGENE IN OVARIAN AND BREAST CARCINOMAS [J].
BELLACOSA, A ;
DEFEO, D ;
GODWIN, AK ;
BELL, DW ;
CHENG, JQ ;
ALTOMARE, DA ;
WAN, MH ;
DUBEAU, L ;
SCAMBIA, G ;
MASCIULLO, V ;
FERRANDINA, G ;
PANICI, PB ;
MANCUSO, S ;
NERI, G ;
TESTA, JR .
INTERNATIONAL JOURNAL OF CANCER, 1995, 64 (04) :280-285
[10]   Phase I, Dose-Escalation Study of BKM120, an Oral Pan-Class I PI3K Inhibitor, in Patients With Advanced Solid Tumors [J].
Bendell, Johanna C. ;
Rodon, Jordi ;
Burris, Howard A. ;
de Jonge, Maja ;
Verweij, Jaap ;
Birle, Diana ;
Demanse, David ;
De Buck, Stefan S. ;
Ru, Qinhua C. ;
Peters, Malte ;
Goldbrunner, Michael ;
Baselga, Jose .
JOURNAL OF CLINICAL ONCOLOGY, 2012, 30 (03) :282-290