MTDH/SND1 protein complex in ERG-mediated transformation and therapeutic resistance
Abstract
Principal Investigator: I began my cancer research work since I was an undergraduate, and I maintained my interest and fascination with cancer biology throughout my training. My long-term goal is to be an independent academic researcher at a university or research institute. For the proposed project, I will be co-mentored by Drs. Valeri Vasioukhin and Peter Nelson at the Fred Hutchinson Cancer Research Center (Fred Hutch). Dr. Vasioukhin is a senior faculty in the Human Biology Division with an extensive history of successful research in prostate and skin cancer. He is an expert in utilization of in vivo models to investigate the functions that are important for prostate cancer genes in cancer initiation, progression, and treatment resistance. Dr. Nelson leads the Program in Prostate Cancer Research at Fred Hutch. He is also the Principal Investigator of the Pacific Northwest Prostate Cancer SPORE (Specialized Program of Research Excellence) and currently serves as Director of its Developmental Research Program. Dr. Nelson is an expert in using genomics analysis and bioinformatics approaches to study the genetic alternation in prostate cancer progression and therapy resistance. Both mentors have an extensive history of successfully training postdoctoral fellows and graduate students. During my training, I will learn important cancer biology research skills that include genetic mouse models of cancer, signal transduction, and genomic and bioinformatics analyses. In addition, I will take courses in bioinformatics and ethical research. I will also have many opportunities to present my research work via talks and posters at Fred Hutch and at national conferences to hone my presentation skills and receive feedback about my work. With this excellent mentorship and the highly supportive environment at Fred Hutch, I will gain necessary knowledge, complete the proposed researched project, and be well-equipped to become an independent prostate cancer investigator. Background and Research Strategy: Prostate cancer is one of the most prevalent cancers among men worldwide. Although localized prostate cancer can be cured by surgical removal and radiotherapy, a small but significant part of patients treated initially for localized prostate cancer will develop a relapse. Androgen deprivation therapy (ADT) is the major therapeutic strategy for relapsed and advanced stage prostate cancer patients, but most patients become resistant to ADT. Therefore, it is necessary to develop novel targeted therapeutic interventions to combat advanced drug-resistant prostate cancer. The ERG gene is the key driver of human prostate cancer. It is aberrantly activated in approximately half of all metastatic ADT-resistant prostate cancer, but presently there are no drugs or treatments that can cure such patients. Therefore, it is important to identify novel therapeutic strategies for ERG-positive prostate cancer. We recently identified novel ERG interacting proteins, Staphylococcal nuclease domain containing 1 (SND1) and Metadherin (MTDH). SND1 and MTDH are heavily implicated in metastasis and drug resistance of breast and many other cancer types, but their role and significance in ERG-positive prostate cancer is not known. Drugs inhibiting SND1 have been developed, but their efficacy in prostate cancer has not been investigated. In this project, I will analyze the significance of MTDH/SND1 in ERG-mediated prostate cancer and determine the sensitivity of human prostate cancer to inhibition of SND1 alone or in combination with existing treatment modalities. Significance: The results of this project will help us understand how overproduction of ERG transforms the prostate gland and helps prostate cancer cells resist drug treatment. I will analyze the role of MTDH/SND1 genes and determine whether inhibition of SND1 alone or in combination with existing drug therapies can eradicate ERG-positive metastatic prostate cancer. If successful
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 10, 2021
- Source ID
- W81XWH2010082
Entities
People
- Sheng-you Liao
Organizations
- Fred Hutchinson Cancer Center
- United States Army