Targeting the PI3K/Akt/mTOR Pathway – Beyond Rapalogs
作者： Ben Markman , Rodrigo Dienstmann , Josep Tabernero
关键词: Receptor tyrosine kinase 、 Cancer 、 Cell biology 、 mTORC1 、 PI3K/AKT/mTOR pathway 、 Signal transduction 、 Cancer research 、 TOR Serine-Threonine Kinases 、 Biology 、 Clinical trial 、 Protein kinase B
摘要: It is well established that the PI3K pathway plays a central role in various cellular processes can contribute to malignant phenotype. Accordingly, pharmacological inhibition of key nodes this signaling cascade has been focus developmental therapeutics. To date, agents targeting upstream receptor tyrosine kinases are best studied and have achieved greatest clinical success. Further downstream, despite efficacy certain tumor types, rapalogs somewhat disappointing clinic. Novel inhibitors PI3K, Akt, mTORC1 2 now passing through early phase trials. hoped these will circumvent some shortcomings lead meaningful benefits for cancer patients.
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Pablo Rodriguez-Viciana, Patricia H. Warne, Ritu Dhand, Bart Vanhaesebroeck, Ivan Gout, Michael J. Fry, Michael D. Waterfield, Julian Downward, PHOSPHATIDYLINOSITOL-3-OH KINASE AS A DIRECT TARGET OF RAS Nature. ,vol. 370, pp. 527- 532 ,(1994) , 10.1038/370527A0
Minh D. To, Jesús Pérez-Losada, Jian-Hua Mao, Allan Balmain, Crosstalk between Pten and Ras signaling pathways in tumor development. Cell Cycle. ,vol. 4, pp. 1185- 1188 ,(2005) , 10.4161/CC.4.9.2039
Howard H. Bailey, Michelle R. Mahoney, David S. Ettinger, William J. Maples, Paula M. Fracasso, Anne M. Traynor, Charles Erlichman, Scott H. Okuno, Phase II study of daily oral perifosine in patients with advanced soft tissue sarcoma Cancer. ,vol. 107, pp. 2462- 2467 ,(2006) , 10.1002/CNCR.22308
Romina Marone, Vladimir Cmiljanovic, Bernd Giese, Matthias P. Wymann, Targeting phosphoinositide 3-kinase—Moving towards therapy Biochimica et Biophysica Acta. ,vol. 1784, pp. 159- 185 ,(2008) , 10.1016/J.BBAPAP.2007.10.003
S. Chandra Shekar, Haiyan Wu, Zheng Fu, Shu-Chin Yip, Nagajyothi, Sean M. Cahill, Mark E. Girvin, Jonathan M. Backer, Mechanism of Constitutive Phosphoinositide 3-Kinase Activation by Oncogenic Mutants of the p85 Regulatory Subunit Journal of Biological Chemistry. ,vol. 280, pp. 27850- 27855 ,(2005) , 10.1074/JBC.M506005200
Keisuke Kurose, Kristie Gilley, Satoshi Matsumoto, Peter H. Watson, Xiao-Ping Zhou, Charis Eng, Frequent somatic mutations in PTEN and TP53 are mutually exclusive in the stroma of breast carcinomas. Nature Genetics. ,vol. 32, pp. 355- 357 ,(2002) , 10.1038/NG1013
Fanyin Meng, Roger Henson, Hania Wehbe–Janek, Kalpana Ghoshal, Samson T. Jacob, Tushar Patel, MicroRNA-21 regulates expression of the PTEN tumor suppressor gene in human hepatocellular cancer Gastroenterology. ,vol. 133, pp. 647- 658 ,(2007) , 10.1053/J.GASTRO.2007.05.022
L. Zhao, P. K. Vogt, Helical domain and kinase domain mutations in p110α of phosphatidylinositol 3-kinase induce gain of function by different mechanisms Proceedings of the National Academy of Sciences of the United States of America. ,vol. 105, pp. 2652- 2657 ,(2008) , 10.1073/PNAS.0712169105
Jeffrey A Engelman, Liang Chen, Xiaohong Tan, Katherine Crosby, Alexander R Guimaraes, Rabi Upadhyay, Michel Maira, Kate McNamara, Samanthi A Perera, Youngchul Song, Lucian R Chirieac, Ramneet Kaur, Angela Lightbown, Jessica Simendinger, Timothy Li, Robert F Padera, Carlos García-Echeverría, Ralph Weissleder, Umar Mahmood, Lewis C Cantley, Kwok-Kin Wong, Effective use of PI3K and MEK inhibitors to treat mutant Kras G12D and PIK3CA H1047R murine lung cancers Nature Medicine. ,vol. 14, pp. 1351- 1356 ,(2008) , 10.1038/NM.1890
Lloyd C Trotman, Pier Paolo Pandolfi, PTEN and p53: who will get the upper hand? Cancer Cell. ,vol. 3, pp. 97- 99 ,(2003) , 10.1016/S1535-6108(03)00022-9