DEPARTMENT OF DEFENSE - CONGRESSIONALLY DIRECTED MEDICAL RESEARCH PROGRAMS

Towards Understanding Ovarian Cancer Progression and Chemotherapy Resistance

Posted September 20, 2017
Jeremy Chien, Ph.D., University of New Mexico School of Medicine

Jeremy Chien, Ph.D., University of New Mexico School of Medicine
Jeremy Chien, Ph.D.
University of New Mexico School of Medicine

Although a significant percentage of ovarian cancer patients respond favorably to initial treatment, the majority will experience recurrence, making ovarian cancer the leading cause of death among gynecological cancers. In many of these recurrences the ovarian cancer cells become resistant to the standard of care regimen of the chemotherapeutic agents carboplatin and paclitaxel, thereby limiting treatment options and leading to poor patient outcomes. The genes and pathways associated with the development of chemotherapy resistance in ovarian cancer are not well understood. In 2009, Dr. Jeremy Chien received an Ovarian Cancer Academy – Early-Career Investigator Award to investigate the mechanisms responsible for chemotherapy resistance and identify potential therapeutic targets that could help sensitize cancer cells to chemotherapy.

The Ovarian Cancer Academy was founded in 2009 by the Ovarian Cancer Research Program (OCRP) as a unique virtual community to provide support to early-career investigators through mentoring, national networking, and a collaborative research environment, with the goal of fostering a lifelong commitment to ovarian cancer research. Dr. Chien is exemplary of the success that can be achieved through such a program. With his 2009 award, Dr. Chien conducted genomics and proteomics studies to uncover the mechanisms underlying chemotherapy resistance. He was able to identify a number of novel candidate genes and proteins that are associated with paclitaxel resistance and could be targeted to increase sensitivity to chemotherapy. Specifically, he was able to validate valosin-containing protein (VCP) as a therapeutic target in ovarian cancer and demonstrate that VCP inhibitors – which are already being tested in clinical trials for solid tumors – cause cell-cycle arrest and trigger cell death in ovarian cancer cells. In addition, he identified extracellular matrix proteins as potential prognostic factors and molecular determinants of early recurrence and death from ovarian cancer.

Since his first OCRP award, Dr. Chien has received three OCRP Pilot Awards in 2010, 2013, and 2016 to expand on his ovarian cancer research. With his 2010 award, he developed a mouse model of tubal carcinogenesis to study early lesions in the fallopian tubes and their spread to the ovaries. The focus of the 2013 award is the FoxM1 pathway, which has been shown to be activated in ovarian cancer and is associated with tumor proliferation, metastasis, and resistance to chemotherapy. Dr. Chien is characterizing the regulation of FoxM1 in ovarian cancer and investigating the use of FoxM1 inhibitors to enhance the cytotoxic effects of conventional chemotherapies. With his most recent OCRP award, Dr. Chien aims to follow up on his previous work with VCP inhibitors and further explore the therapeutic potential of these compounds for treating ovarian cancer tumors that have become resistant to chemotherapy. The ultimate goal of Dr. Chien’s research is to create a database, a "genome-wide cancer toolkit," to determine which genes contribute to chemotherapy resistance. The information collected in this database will likely impact other cancer types beyond ovarian cancer.

Dr. Chien’s continued commitment to ovarian cancer research embodies the overarching goal of the Ovarian Cancer Academy to develop highly productive and successful ovarian cancer researchers. His research could help determine which subtypes of ovarian cancer will become resistant to chemotherapy, thereby helping to advance personalized treatments for women battling this disease. Dr. Chien recently accepted the position of Associate Professor in the Department of Internal Medicine, Division of Molecular Medicine, at the University of New Mexico School of Medicine and will join the UNM Comprehensive Cancer Center as an Endowed Professor in Cancer Genomics and Target Discovery, where he will continue his innovative research to further our understanding of chemotherapy resistance in ovarian cancer.

Links:

University of New Mexico Comprehensive Cancer Center

Public and Technical Abstracts: Integrative Functional Genomics and Proteomics to Uncover Mechanisms of Resistance to Chemotherapy in Ovarian Cancer

Ovarian Mouse Models with Targeted Fallopian Tubal Carcinogenesis

Targeting FoxM1 Pathway in Ovarian Cancer

Exploiting ER Stress Pathway as a Target of Vulnerability in Ovarian Cancer

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Last updated Wednesday, September 20, 2017