2/2 Drug Development and Capacity Building: A UCR/CoH-CCC Partnership (Pilot Project 1)

2/2 药物开发和能力建设：UCR/CoH-CCC 合作伙伴关系（试点项目 1）

• 批准号: 10006592
• 负责人: ERNEST MARTINEZ
• 金额: $ 11.14万
• 依托单位: UNIVERSITY OF CALIFORNIA RIVERSIDE
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-02 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10006592
• 关键词: Accounting; Acetyl Coenzyme A; Acetylation; African; African American; Automobile Driving; Biological; Biological Markers; Biological Response Modifier Therapy; Biology; California; Chromatin; Chromatin Structure; Cities; ERBB2 gene; Early Diagnosis; Early treatment; Estrogen receptor positive; Ethnic group; European; Frequencies; Fresh Tissue; Genetic; Genetic Transcription; Glycolysis; Goals; Hispanics; Histones; Incidence; Indigenous American; Latina; Los Angeles; Low income; Malignant - descriptor; Metabolic; Metabolism; Mexico; Mitochondria; Modeling; Mus; Native Americans; Neoadjuvant Therapy; Not Hispanic or Latino; Oncogenic; Outcome; Pharmaceutical Preparations; Pilot Projects; Play; Predictive Factor; Production; Prospective Studies; Research Personnel; Resistance; Resources; Retrospective Studies; Role; Signal Transduction; Socioeconomic Factors; Testing; Translating; Woman; c-myc Genes; cancer cell; cancer subtypes; chemotherapy; drug development; ethnic diversity; high throughput screening; histone acetyltransferase; improved; malignant breast neoplasm; metaplastic cell transformation; mortality; non-histone protein; outcome forecast; overexpression; targeted agent; transcription factor; triple-negative invasive breast carcinoma

Abstract: Currently there are no biomarkers to separate good from poor prognosis luminal B breast cancers. Poor prognosis luminal B breast cancers are only identified after a woman fails to respond to neo-adjuvant therapy and options for cure are limited. While recent efforts have focused on developing targeted agents for triple- negative breast cancer, luminal B breast cancer has been understudied, particularly in Latina/Hispanic women. Here, we aim to investigate the biology of aggressive luminal B breast cancers in Latina/Hispanic women with the overall goal of improving early detection and survival. Overexpression of the oncogenic transcription factor c-MYC (MYC) promotes malignant transformation and predicts poor prognosis in women with luminal B breast cancers. Recent studies show that, relative to Northern European Whites, Black women with luminal B breast cancers have a high-frequency of MYC-overexpression[5]. Preliminary studies provide evidence that MYC is also frequently overexpressed in Latinas. UC Riverside (UCR) P20 PI Dr. Ernest Martinez studies the mechanistic role of MYC-acetylation in promoting glycolysis and cellular transformation. City of Hope (CoH) investigator, Dustin Schones studies the role of glycolysis in driving abnormal chromatin acetylation and aberrant transcription. In this pilot, we aim to leverage these discoveries to target MYC-acetylation for drug development. In this Early Drug Pipeline Pilot study, we aim to test the hypothesis that MYC-driven mitochondrial Acetyl-CoA overproduction in luminal B breast cancer 1) promotes abnormal chromatin opening and enhances the oncogenic functions of MYC and 2) predicts poor survival. Findings will be translated to test whether MYC-acetylation is a promising target for early detection and/or treatment of luminal B breast cancer in Latinas. Aim 1 will test whether chromatin acetylation and/or acetylation of the MYC oncogenic transcription factor predicts poor prognosis in Southern California Latinas with luminal B breast cancer. Aim 2 will target the acetylation/metabolic functions of MYC in high-throughput screening and mouse PDX models derived from MYC+ luminal B breast cancers from Los Angeles Latina women.

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