PI 3-Kinase and Interplay with Other Signaling Pathways

描述（由申请人提供）：要求支持由Christian Rommel， Kevan M. Shokat和Jose Baselga组织的题为PI 3-激酶及其与其他信号通路的相互作用的Keystone专题会议。会议将于2013年2月24日至3月1日在科罗拉多州的基斯顿举行。如何调节代谢途径以满足肿瘤细胞的独特需求尚不清楚，但越来越多的证据表明，癌细胞中的代谢调节与控制细胞生长和增殖的信号转导途径密切相关。PI3K-Akt-mTOR信号通路是控制肿瘤细胞生长、存活和运动以响应致癌信号和细胞外信号的主要机制之一。导致该通路不适当激活的遗传事件在许多癌症中很常见，因此是基础癌症研究和肿瘤学药物发现工作的重点。虽然最初被建模为一个独立的线性信号级联，但今天很明显，PI3K通路在与其他重要信号通路的垂直和互反馈调节中也作为串扰的中心枢纽。该领域最令人兴奋的进展之一是针对这一途径的新抑制剂的开发。然而，抑制PI3K/Akt/mTOR信号的单个或多个亚型的原理仍然是一个激烈争论的主题。本次会议旨在汇集来自学术界和工业界的科学家和临床医生，利用人类病理生理学和遗传学、临床前模型和PI3K通路抑制剂的临床数据，讨论靶向PI3K及其相关疾病通路的机会和缺点。关于肿瘤代谢的联合会议将增加跨学科互动的机会。

DESCRIPTION (provided by applicant): Support is requested for a Keystone Symposia meeting entitled PI 3-Kinase and Interplay with Other Signaling Pathways, organized by Christian Rommel, Kevan M. Shokat and Jose Baselga. The meeting will be held in Keystone, Colorado from February 24 - March 1, 2013. How metabolic pathways are regulated to meet the unique needs of tumor cells is not well understood, but mounting evidence suggests that metabolic regulation in cancer cells is intimately linked with the signal transduction pathways that control cell growth and proliferation. The PI3K-Akt-mTOR signaling pathway is one of the primary mechanisms for controlling tumor cell growth, survival, and motility in response to oncogenic signaling and extracellular cues. Genetic events resulting in inappropriate activation of this pathway are common in many cancers and, as a result, are a focus of both basic cancer research and drug discovery efforts in oncology. Although originally modeled as an independent and linear signaling cascade, today it is evident that the PI3K pathway also functions as a central hub for cross-talk in both vertical as well as reciprocal feedback regulation with other important signaling pathways. One of the most exciting advances in the field is the development of new inhibitors against this pathway. However, the rationale for inhibiting individual or multipl isoforms of PI3K/Akt/mTOR signaling remains a subject of intense debate. This meeting aims to bring together scientists and clinicians from academia and industry to discuss the opportunities and liabilities of targeting the PI3K- and related pathways in disease, drawing on human pathophysiology and genetics, preclinical models and clinical data with PI3K pathway inhibitors. A joint meeting addressing Tumor Metabolism will enhance opportunities for interdisciplinary interactions.