Defining biomarkers to predict sensitivity to PI3K/Akt/mTOR pathway inhibitors in breast cancer.
Defining biomarkers to predict sensitivity to PI3K/Akt/mTOR pathway inhibitors in breast cancer.
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DOI：
10.1016/j.ctrv.2012.11.002
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发表时间：
2013-06
影响因子：
11.8
通讯作者：
Blumenschein GR Jr
中科院分区：
文献类型：
--
作者：
Gonzalez-Angulo AM;Blumenschein GR Jr
生物标记物的识别和验证对于整合新的靶向药物治疗癌症越来越重要。磷脂酰肌醇3-激酶(PI3K)/Akt/哺乳动物靶点雷帕霉素(MTOR)通路是乳腺癌治疗的重要靶点，针对PI3K/Akt/mTOR轴不同结节的抑制剂正在开发中。识别生物标记物以帮助选择最有可能从这些治疗中受益的患者是一个基本的未得到满足的需求。检索Medline和国际会议摘要，寻找乳腺癌患者和临床前模型中对PI3K/Akt/mTOR途径抑制剂敏感的标志物的证据。临床前证据表明，PI3K/Akt/mTOR通路异常，特别是在PIK3CA中，可能识别出乳腺癌患者中优先对PI3K/Akt/mTOR抑制剂有反应的亚群。然而，需要更多的标记物来确定所有对PI3K/Akt/mTOR通路抑制从头开始敏感的患者。验证这些生物标志物的早期临床研究还没有定论。为了检测乳腺癌患者对PI3K/Akt/mTOR通路抑制剂敏感性的候选生物标志物，并根据分子改变的模式，确定某些PI3K/Akt/mTOR通路抑制剂是否更适用于不同的亚型，需要进行前瞻性、充分设计和强有力的临床试验。
Identification and validation of biomarkers is increasingly important for the integration of novel targeted agents in the treatment of cancer. The phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway represents a promising therapeutic target in breast carcinoma, and inhibitors targeting different nodes of the PI3K/Akt/mTOR axis are in development. Identification of biomarkers to help select patients who are most likely to benefit from these treatments is an essential unmet need. MEDLINE and international conference abstracts were searched for evidence of markers of sensitivity to PI3K/Akt/mTOR pathway inhibitors in breast cancer patients and preclinical models. Preclinical evidence suggests that PI3K/Akt/mTOR pathway aberrations, notably in PIK3CA, may identify a subpopulation of patients with breast cancer who preferentially respond to PI3K/Akt/mTOR inhibitors. However, additional markers are needed to identify all patients with de novo sensitivity to PI3K/Akt/mTOR pathway inhibition. Early clinical studies to validate these biomarkers have as yet been inconclusive. Prospective, adequately designed and powered clinical trials are needed to test candidate biomarkers of sensitivity to PI3K/Akt/mTOR pathway inhibitors in patients with breast cancer, and to determine whether certain PI3K/Akt/mTOR pathway inhibitors are more appropriate in different subtypes depending on the pattern of molecular alteration.
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影响因子：
11.5
作者：
Hoeflich, Klaus P.;O'Brien, Carol;Lackner, Mark R.
通讯作者：
Lackner, Mark R.
影响因子：
64.5
作者：
Knight, Zachary A.;Gonzalez, Beatriz;Shokat, Kevan M.
通讯作者：
Shokat, Kevan M.
影响因子：
64.8
作者：
Garnett, Mathew J.;Edelman, Elena J.;Heidorn, Sonja J.;Greenman, Chris D.;Dastur, Anahita;Lau, King Wai;Greninger, Patricia;Thompson, I. Richard;Luo, Xi;Soares, Jorge;Liu, Qingsong;Iorio, Francesco;Surdez, Didier;Chen, Li;Milano, Randy J.;Bignell, Graham R.;Tam, Ah T.;Davies, Helen;Stevenson, Jesse A.;Barthorpe, Syd;Lutz, Stephen R.;Kogera, Fiona;Lawrence, Karl;McLaren-Douglas, Anne;Mitropoulos, Xeni;Mironenko, Tatiana;Thi, Helen;Richardson, Laura;Zhou, Wenjun;Jewitt, Frances;Zhang, Tinghu;O'Brien, Patrick;Boisvert, Jessica L.;Price, Stacey;Hur, Wooyoung;Yang, Wanjuan;Deng, Xianming;Butler, Adam;Choi, Hwan Geun;Chang, JaeWon;Baselga, Jose;Stamenkovic, Ivan;Engelman, Jeffrey A.;Sharma, Sreenath V.;Delattre, Olivier;Saez-Rodriguez, Julio;Gray, Nathanael S.;Settleman, Jeffrey;Futreal, P. Andrew;Haber, Daniel A.;Stratton, Michael R.;Ramaswamy, Sridhar;McDermott, Ultan;Benes, Cyril H.
通讯作者：
Benes, Cyril H.
影响因子：
50.3
作者：
Gewinner C;Wang ZC;Richardson A;Teruya-Feldstein J;Etemadmoghadam D;Bowtell D;Barretina J;Lin WM;Rameh L;Salmena L;Pandolfi PP;Cantley LC
通讯作者：
Cantley LC
影响因子：
45.3
作者：
FISHER, B;REDMOND, C;FRELICK, R
通讯作者：
FRELICK, R