Role of Rab1 in Cell Growth and Cancer

Rab1 在细胞生长和癌症中的作用

基本信息

批准号：
8583926
负责人：
STEVEN ZHENG
金额：
$ 32.99万
依托单位：
RBHS -CANCER INSTITUTE OF NEW JERSEY
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-08-14 至 2018-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8583926
关键词：
Amino Acids Antineoplastic Agents Biological Biological Markers Biology Breast CCI-779 Cancer Cell Growth Cell Proliferation Cell physiology Cells Cellular biology Complex Data Diabetes Mellitus Disease Drug Targeting Ductal Carcinoma Ductal Epithelium Epithelial Cells Epithelium FDA approved Functional disorder Goals Golgi Apparatus Growth Guanosine Triphosphate Phosphohydrolases Heart Diseases Heart Hypertrophy Human Hyperplasia Intraductal Hyperplasia Lead Malignant Neoplasms Mammals Mammary gland Mediator of activation protein Metabolism Molecular Normal Cell Nutrient Outcome Pathogenesis Pathway interactions Patients Pharmaceutical Preparations Play Process Protein Kinase Regulation Renal carcinoma Research Role SDZ RAD Signal Transduction Sirolimus Stimulation of Cancer Cell Growth Stimulus Testing Tumorigenicity Vesicle Yeasts base cancer cell cancer therapy cancer type cell growth ductal breast carcinoma human disease inhibitor/antagonist insight mTOR protein malignant breast neoplasm novel overexpression public health relevance response trafficking

项目摘要

DESCRIPTION (provided by applicant): Mechanistic or mammalian target of rapamycin (mTOR) is a central controller of cell growth and proliferation in response to mitogenic and nutrient signals. mTOR pathway is frequently hyper-activated in human cancers, leading to uncontrolled cancer growth. Because cancer cells are often 'addicted' to elevated mTOR signaling, rendering mTOR a desirable cancer drug target. The highly specific mTOR inhibitors rapamycin analogs (rapalogs) are FDA-approved anti-cancer drugs for advanced renal and breast cancers. However, their efficacy is limited by lack of understanding of what patients are responsive to rapalog therapy. Therefore, a detailed understanding of mTOR signaling will is of considerable significance to basic biology and cancer therapy. In this application, we will investigate the mechanism of stimulation of cell growth and cancer by Rab1, a novel mTOR activator we recently identified. We will further study the role of Rab1 in the pathobiology and targeted therapy of breast cancer. We anticipate that successful completion of this project will help answer some long-standing questions on cell regulation and enable individualized cancer therapy.

描述（由申请人提供）：雷帕霉素的机械或哺乳动物靶标（MTOR）是响应有丝分裂和营养信号的细胞生长和增殖的中心控制器。 MTOR途径经常在人类癌症中过度激活，从而导致不受控制的癌症生长。因为癌细胞通常会“上瘾” MTOR信号传导升高，从而使MTOR成为理想的癌症药物靶标。高度特异性的MTOR抑制剂雷帕霉素类似物（Rapalogs）是FDA批准的抗癌药物，用于晚期肾脏和乳腺癌。但是，由于缺乏对患者对Rapalog治疗的反应，它们的功效受到限制。因此，对MTOR信号传导的详细了解对基本生物学和癌症治疗具有相当大的意义。在此应用中，我们将通过RAB1（我们最近确定的一种新型的MTOR激活剂Rab1）研究刺激细胞生长和癌症的机理。我们将进一步研究RAB1在病理生物学和靶向乳腺癌靶向治疗中的作用。我们预计该项目的成功完成将有助于回答一些有关细胞调节的长期问题，并实现个性化的癌症治疗。