A role of FAM3B in suppressing prostate cancer progression

FAM3B 在抑制前列腺癌进展中的作用

• 批准号: 9892167
• 负责人: Yan Dong
• 金额: --
• 依托单位: SOUTHEAST LOUISIANA VETERANS HEALTH CARE
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-04-01 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9892167
• 关键词: Address; Animal Model; Area; Attenuated; Automobile Driving; Biochemical; Biological; Biological Markers; Biological Models; Biology; Cancer Relapse; Castration; Cell Line; Cells; Chromosomal Insertion; Chromosomal Rearrangement; Clinical; Data Set; Development; Diagnosis; Disease; Disease Progression; ERG gene; Ectopic Expression; Enzymes; Family; Foundations; Future; Genes; Genetic; Glycolysis; Glycolysis Pathway; Goals; Growth; Health; Healthcare; Human; Knock-out; Knockout Mice; Knowledge; Malignant Neoplasms; Malignant neoplasm of prostate; Mediating; Metastatic Neoplasm to the Bone; Metastatic Prostate Cancer; Metastatic to; Modeling; Neoplasm Metastasis; Osteolytic; Oxidative Phosphorylation; Patient-Focused Outcomes; Patients; Prostate; Prostate Cancer therapy; Research; Research Design; Resistance; Role; Sampling; TMPRSS2 gene; Testing; Therapeutic; Therapeutic Trials; Tumor stage; VCaP; Validation; Veterans; Xenograft Model; Xenograft procedure; aerobic glycolysis; anticancer research; assay development; base; biomarker-driven; clinically relevant; design; diminished oxidative phosphorylation; effective therapy; genetic makeup; glucose metabolism; inhibitor/antagonist; interstitial; novel; novel marker; novel therapeutics; patient population; preclinical study; prostate cancer model; prostate cancer progression; subcutaneous; trial design

The recent development and FDA approval of a number of new drugs heralded a new era of prostate cancer therapy. However, metastatic prostate cancer remains a fatal disease. Thus, there is a critical need to identify prostate cancers that will progress to metastatic and develop effective therapies to treat them early to stop disease progression. The proposed study addresses these critical areas of need. In our preliminary studies, via an unbiased analysis of close to 400 clinical samples and subsequent experimental validation, we identified loss of the FAM3B (family with sequence similarity 3B) gene as a potential driver of metastatic progression of prostate cancer. We further found that FAM3B loss leads to diminished oxidative phosphorylation and enhanced aerobic glycolysis, which is a known mechanism of prostate cancer progression. Building on these novel findings, we hypothesize that loss of FAM3B drives prostate cancer progression to an advanced stage and that this is mediated, at least in part, by suppressing oxidative phosphorylation and promoting aerobic glycolysis. This hypothesis will be tested by two specific aims that employ clinically relevant model systems and clinical datasets. Aim 1 will dissect the mechanism by which FAM3B loss modulates glucose metabolism in driving disease progression. Aim 2 will establish FAM3B loss as a driver of prostate cancer progression. By interrogating the FAM3B-glucose-metabolism axis from a mechanistic and functional perspective, the proposed study will reveal a new and important mechanism driving prostate cancer progression, provide a new marker to better identify those patients, including the Veterans, with aggressive disease so that they can be treated early and effectively. Moreover, understanding the precise mechanisms by which FAM3B loss impacts glucose metabolism and drives disease progression will aid in future design of inhibitors that specifically target FAM3B-low prostate cancer. Overall, the application addresses an area that is highly relevant to the prostate cancer field, from both biological and translational perspectives.

最近的发展和FDA批准的一些新药预示着前列腺癌的新时代