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

September 10, 2012

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 , including docetaxel. They identified a cell population expressing markers of embryonic development. In addition, these cells displayed cancer stem , 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 had more of these cancer "stem" cells.

"This is the first time these so-called cancer of prostate have been identified as the basis for 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 could lead to the development of new tests for early , 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 .

Explore further: Cancer stem cell vaccine in development shows antitumor effect

Related Stories

Cancer stem cell vaccine in development shows antitumor effect

April 2, 2012
Scientists may have discovered a new paradigm for immunotherapy against cancer by priming antibodies and T cells with cancer stem cells, according to a study published in Cancer Research, a journal of the American Association ...

Inhibiting Hedgehog signaling pathway may improve pancreatic cancer treatment

June 19, 2012
Combining a new targeted therapy with standard chemotherapy may help defeat pancreatic cancer, according to results presented at the American Association for Cancer Research's Pancreatic Cancer: Progress and Challenges conference, ...

Recommended for you

Drug combination may improve impact of immunotherapy in head and neck cancer

September 21, 2017
Checkpoint inhibitor-based immunotherapy has been shown to be very effective in recurrent and metastatic head and neck cancer but only in a minority of patients. University of California San Diego School of Medicine researchers ...

Whole food diet may help prevent colon cancer, other chronic conditions

September 21, 2017
A diet that includes plenty of colorful vegetables and fruits may contain compounds that can stop colon cancer and inflammatory bowel diseases in pigs, according to an international team of researchers. Understanding how ...

New kinase detection method helps identify targets for developing cancer drugs

September 21, 2017
Purdue University researchers have developed a high-throughput method for matching kinases to the proteins they phosphorylate, speeding the ability to identify multiple potential cancer drug targets.

Poliovirus therapy induces immune responses against cancer

September 20, 2017
An investigational therapy using modified poliovirus to attack cancer tumors appears to unleash the body's own capacity to fight malignancies by activating an inflammation process that counter's the ability of cancer cells ...

Scientists restore tumor-fighting structure to mutated breast cancer proteins

September 20, 2017
Scientists at the Virginia Tech Carilion Research Institute have successfully determined the full architecture of the breast cancer susceptibility protein (BRCA1) for the first time. This three-dimensional information provides ...

Brain cancer growth halted by absence of protein, study finds

September 20, 2017
The growth of certain aggressive brain tumors can be halted by cutting off their access to a signaling molecule produced by the brain's nerve cells, according to a new study by researchers at the Stanford University School ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.