Researchers reveal a chemo-resistant cancer stem cell as cancer's 'Achilles' heel'

Breakthrough may lead to the development of novel cancer therapies that strike cancer at its source

2012-09-10

(Press-News.org) Scientists at Mount Sinai School of Medicine have discovered a subpopulation of cells that display cancer stem cell properties and resistance to chemotherapy, and participate in tumor progression. This breakthrough could lead to the development of new tests for early cancer diagnosis, prognostic tests, and innovative therapeutic strategies, as reported in Cancer Cell.

Resistance to chemotherapy is a frequent and devastating phenomenon that occurs in cancer patients during certain treatments. Unfortunately, tumors that initially respond to chemotherapy eventually become resistant to it, contributing to tumor progression and death. The study reveals that these new cancer "stem" cells, which have not been differentiated into more specific cell types, are capable of multiplying despite being exposed to chemotherapy, while differentiated cells die.

Led by Carlos Cordon-Cardo, MD, PhD, Chair of Pathology, and Josep Domingo-Domenech, MD, PhD, Assistant Professor of Pathology at Mount Sinai, the research team generated cellular models of drug resistance by treating prostate tumor cell lines with increasing doses of the common chemotherapy drugs, including docetaxel. They identified a cell population expressing markers of embryonic development. In addition, these cells displayed cancer stem cell functions, including the capacity to initiate tumor cell growth. Next, the team evaluated human tissue samples of prostate cancer and found that patients with more aggressive or metastatic tumors had more of these cancer "stem" cells.

"This is the first time these so-called cancer stem cells of prostate have been identified as the basis for drug resistance and tumor progression, indicating that they are cancer's 'Achilles Heel,'" said Dr. Cordon-Cardo. "These findings are the culmination of more than six years of innovative research, which has led to the successful unveiling of cancer characteristics that are critical to understanding how the disease works and progresses."

The study also defines a new therapeutic strategy for patients with prostate cancer, consisting of a combination of standard chemotherapy and two pharmacological agents that inhibit key signaling pathways associated with embryonic development and cell differentiation. Results showed that chemotherapy eliminated differentiated tumor cells, whereas the signaling pathway inhibitors selectively depleted the cancer stem cell population. Some of these inhibitors are already in clinical trials, and some are FDA-approved.

"By targeting these newly identified cancer 'stem' cells, we are attacking the foundation of tumor growth, rather than treating the symptoms of it," said Dr. Domingo-Domenech. "The novel discovery of this cell population could lead to the development of new tests for early cancer diagnosis, prognostic tests, and innovative therapeutic strategies."

Ongoing studies suggest that this new cell type exist in other tumor types such as breast cancer, colon cancer, bladder cancer and lung cancer. Dr. Cordon-Cardo's team is studying these disease areas to determine the presence and impact of these cancer cells.

###About The Mount Sinai Medical Center

The Mount Sinai Medical Center encompasses both The Mount Sinai Hospital and Mount Sinai School of Medicine. Established in 1968, Mount Sinai School of Medicine is one of the leading medical schools in the United States. The Medical School is noted for innovation in education, biomedical research, clinical care delivery, and local and global community service. It has more than 3,400 faculty in 32 departments and 14 research institutes, and ranks among the top 20 medical schools both in National Institutes of Health (NIH) funding and by US News and World Report.

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 16th 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/.

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