Researchers Identify Key Protein in Treatment-Resistant Prostate Cancer
Prostate cancer is one of the most common forms of cancer in men and the leading cause of cancer deaths in white, African American, and Hispanic men, according to the Centers for Disease Control. However, it remains unclear why, despite treatment, some prostate cancers progress and may become fatal. Researchers at Robert Wood Johnson Medical School, part of Rutgers, The State University of New Jersey, who are studying the underlying mechanisms that cause invasive tumor growth have identified a key transcription factor that is overproduced in treatment-resistant prostate cancer, as well as the two protein kinases that trigger the process. The findings, published in Molecular Cancer Research, could be utilized to develop treatments for prostate cancer that is resistant to current therapies.
Study Findings
The research team, led by Joseph Fondell, PhD, Associate Professor of Pharmacology, found that in clinically localized human prostate cancer, the key transcription factor MED1 is overexpressed and could potentially be used as a biomarker for aggressive cancer. “As MED1 is a known coactivator of androgen receptors, the overexpression of MED1 is thought to facilitate alternative gene-expression patterns that drive treatment-resistant cancer cell growth in the prostate,” Dr. Fondell said.
“Our study showed for the first time that MED1 expression is elevated in malignant cells of a statistically significant number of patients with clinical prostate cancer and that this overexpression correlates with an increase in cancer cell growth and invasiveness,” said Feng Jin, PhD, a former graduate student in Dr. Fondell’s lab and first author on the study. “In addition to accelerated tumor growth, our study showed that overexpression of MED1 may also be involved with inflammation of the prostate.”
Further study of the process using mouse models that mimic human prostate cancer, showed that two protein kinases, ERK and PI3K/AKT, were overactive and responsible for MED1 overproduction, ultimately accelerating the progression and spread of prostate cancer.
‘A Novel Target for New Therapies’
“Whereas the current treatment approach for prostate cancer is to prohibit androgen production and signaling, our findings indicate that MED1 could represent a novel target for new therapies that stop the process at the molecular level, before prostate cancer can progress to an advanced stage,” added Dr. Fondell.
The research was supported by Department of Defense Prostate Cancer Research Program Award W81XWH-10-1-0227.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
