Research on a soy-based treatment for colorectal cancer, a promising agent in ovarian cancer, and a new drug target for advanced prostate cancer was presented at the American Association for Cancer Research 2013 Annual Meeting. The meeting took place April 6-10, 2013 in Washington, DC.
Natural Product From Soy May Be Effective in Combination with Chemotherapy
The development of colorectal cancer (CRC) is largely driven by cellular signaling in the Wnt pathway, a network of proteins critical to cellular growth. Hyperactivity of the Wnt signaling pathway occurs in more than 85 percent of colon and rectal cancers. Previous research has shown that genistein, a natural supplement containing soy, modulates Wnt signaling through epigenetic mechanisms.
Led by Randall Holcombe, MD, and Sofya Pintova, MD, both from Mount Sinai, the research team treated colon cancer cell lines with genistein and found that it inhibited cell growth and blocked Wnt signaling hyperactivity. The findings are counter to some other tumor types, such as breast, for which soy, because it has estrogen-like properties, increases the risk of developing tumors. Drs. Holcombe and Pintova are launching a clinical trial later this year for patients with metastatic colorectal cancer, which utilizes genistein in combination with chemotherapy based on this research.
"Genistein is a natural product with low toxicity and few side effects and our research shows that it may be beneficial in treating colorectal cancer," said Randall Holcombe, MD, Professor of Medicine in the Division if Hematology and Oncology at the Icahn School of Medicine at Mount Sinai. "This is an exciting area of research and we look forward to studying the benefits of this compound as an adjunctive treatment in colorectal cancer in humans."
Mount Sinai Researchers Identify Promising Therapy for Treatment-Resistant Ovarian Cancer
Platinum-based therapies are the standard of care in treating ovarian cancer, however 60 percent of patients relapse requiring additional treatment. During cancer development, certain proteins that might otherwise block tumor growth are inappropriately shuttled out of the cell's nucleus, and rendered unable to attack a tumor's mutated genome. Researchers led by John A. Martignetti, MD, PhD, Associate Professor of Genetics and Genomic Sciences and Oncological Sciences at Mount Sinai, in collaboration with investigators at Karyopharm Therapeutics, inhibited a nuclear shuttle protein called exportin 1 (XPO1, also called CRM1) using a novel class of drugs called a selective inhibitor of nuclear export (SINE) that can be taken by mouth.Ying Chen, PhD, a post-doctoral student in Dr. Martignetti's laboratory, injected tumor cells removed from ovarian cancer patients treated at Mount Sinai into mice, and then treated them with a SINE XPO1 inhibitor, KPT-330. All mice treated with KPT-330 had no visible evidence of tumor and survived six times longer than control mice.
In the current study led by Yixuan Gong, PhD, in Dr. Oh's lab, the researchers show for the first time that resistance to androgen therapy, the most common treatment for prostate cancer, was associated with TIMP-1 overproduction in both prostate cancer patients and in cell culture models. They found that two signaling pathways called MEK and NF-©§B were critical for TIMP-1 production in certain prostate cells and the production could be completely blocked by drugs that inhibit the pathways.
"Disrupting TIMP-1 signaling prevented androgen resistance providing a promising drug target for this hard-to-treat tumor type," said Dr. Gong. "We look forward to further investigating drugs that block TIMP-1 in a clinical setting."
The Tisch Cancer Institute (TCI) is a world-class translational cancer institute established in December 2007. TCI has recruited more than 30 acclaimed physicians and researchers specializing in basic research, clinical research, and population science; built outstanding programs in solid tumor oncology; enhanced existing robust programs in hematological malignancies; and advanced the study of cancer immunology and vaccine therapy. The completion of the Leon and Norma Hess Center for Science and Medicine in 2012 is enabling the recruitment of up to 20 additional cancer researchers on two full research floors, with 48,000 square feet of space dedicated to cancer research.
To learn more about TCI, visit http://www.mountsinai.org/patient-care/service-areas/cancer.
To learn more about the Hess Center, visit http://icahn.mssm.edu/about-us/hess-center.About The Mount Sinai Medical Center
The Mount Sinai Hospital, founded in 1852, is a 1,171-bed tertiary- and quaternary-care teaching facility and one of the nation's oldest, largest and most-respected voluntary hospitals. In 2011, US News and World Report ranked The Mount Sinai Hospital 14th on its elite Honor Roll of the nation's top hospitals based on reputation, safety, and other patient-care factors. Mount Sinai is one of 12 integrated academic medical centers whose medical school ranks among the top 20 in NIH funding and US News and World Report and whose hospital is on the US News and World Report Honor Roll. Nearly 60,000 people were treated at Mount Sinai as inpatients last year, and approximately 560,000 outpatient visits took place.
For more information, visit http://www.mountsinai.org/.Find Mount Sinai on:
Further reports about: > Cancer > Karyopharm > Medical Wellness > Medicine > NIH > Sinai > Translational Research > Wnt signaling > XPO1 > cancer research > colorectal cancer > epigenetic mechanism > genetic mechanism > identify > ovarian > ovarian cancer > prostate cancer > rectal cancer > signaling pathway
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