像依維莫司這樣的藥物，能夠靶向定位mTOR蛋白,，它們被用于治療一些癌癥,，但并不是所有的蛋白都會對治療產(chǎn)生應(yīng)答。來自意大利都靈大學醫(yī)學院的一個研究團隊已經(jīng)發(fā)現(xiàn)了一種新方法,，能幫助預(yù)測哪些病人會對這樣的藥物有反應(yīng),。
確切地說，該研究團隊發(fā)現(xiàn),，在體外存在基因PIK3CA變異的人類癌細胞會對依維莫司產(chǎn)生應(yīng)答,，而只有當同樣存在KRAS基因變異時才沒有應(yīng)答。更為重要的一點是,，在一些轉(zhuǎn)移性癌癥患者身上,，KRAS基因變異的存在與依維莫司療法的應(yīng)答相關(guān)。研究結(jié)果表明,，通過觀察腫瘤中PIK3CA和KRAS基因的變異,，將有可能預(yù)測患者對靶向mTOR的藥物療法是否有效,。
研究人員表示，這項研究將極有可能改變臨床策略,，但還需要大量研究來證實這項發(fā)現(xiàn),。這項研究結(jié)果發(fā)布在Journal of Clinical Investigation雜志上。(生物谷Bioon.com)
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>>>借著上海世博會的良好契機,，"第一屆腫瘤基礎(chǔ)和轉(zhuǎn)化醫(yī)學國際研討會"將于2010年10月12日在中國上海盛大開幕，這將為廣大活躍在腫瘤基礎(chǔ)和轉(zhuǎn)化醫(yī)學第一線的科研工作者提供一個互動交流的平臺,。
會議官方網(wǎng)站：www.cancerasia.org
生物谷推薦原文出處：
J Clin Invest. doi:10.1172/JCI37539.
Deregulation of the PI3K and KRAS signaling pathways in human cancer cells determines their response to everolimus
Federica Di Nicolantonio1,2, Sabrina Arena1, Josep Tabernero3, Stefano Grosso4,5, Francesca Molinari6, Teresa Macarulla3, Mariangela Russo1, Carlotta Cancelliere1, Davide Zecchin1, Luca Mazzucchelli6, Takehiko Sasazuki7, Senji Shirasawa8, Massimo Geuna9, Milo Frattini6, José Baselga3, Margherita Gallicchio10, Stefano Biffo4,5 and Alberto Bardelli1,2
1Laboratory of Molecular Genetics, Institute for Cancer Research and Treatment, IRCC, University of Turin Medical School, Turin, Italy.
2FIRC, Institute of Molecular Oncology, Milan, Italy.
3Medical Oncology Department, Vall d’Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain.
4Laboratory of Molecular Histology and Cell Growth, Division of Oncology, San Raffaele Scientific Institute, Milan, Italy.
5DISAV, University of Eastern Piedmont, Alessandria, Italy.
6Laboratory of Molecular Diagnostic, Istituto Cantonale di Patologia, Locarno, Switzerland.
7International Medical Center of Japan, Tokyo, Japan.
8Department of Cell Biology, School of Medicine, Fukuoka University, Fukuoka, Japan.
9Laboratory of Immunopathology, Anatomia Patologica, Ospedale Mauriziano Umberto I, Turin, Italy.
10Department of Anatomy, Pharmacology, and Forensic Medicine, University of Turin, Turin, Italy.
Personalized cancer medicine is based on the concept that targeted therapies are effective on subsets of patients whose tumors carry specific molecular alterations. Several mammalian target of rapamycin (mTOR) inhibitors are in preclinical or clinical trials for cancers, but the molecular basis of sensitivity or resistance to these inhibitors among patients is largely unknown. Here we have identified oncogenic variants of phosphoinositide-3-kinase, catalytic, α polypeptide (PIK3CA) and KRAS as determinants of response to the mTOR inhibitor everolimus. Human cancer cells carrying alterations in the PI3K pathway were responsive to everolimus, both in vitro and in vivo, except when KRAS mutations occurred concomitantly or were exogenously introduced. In human cancer cells with mutations in both PIK3CA and KRAS, genetic ablation of mutant KRAS reinstated response to the drug. Consistent with these data, PIK3CA mutant cells, but not KRAS mutant cells, displayed everolimus-sensitive translation. Importantly, in a cohort of metastatic cancer patients, the presence of oncogenic KRAS mutations was associated with lack of benefit after everolimus therapy. Thus, our results demonstrate that alterations in the KRAS and PIK3CA genes may represent biomarkers to optimize treatment of patients with mTOR inhibitors.
