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Researchers Target ‘Cell Sleep’ to Lower Chances of Cancer Recurrence

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Key Points

  • Although imatinib has been shown to be an effective targeted therapy for gastrointestinal stromal tumors (GISTs), GISTs rapidly develop resistance to the treatment, and complete cancer remission using imatinib is rare.
  • Inhibition of the DREAM complex, a key regulator of quiescence, significantly increased imatinib-induced apoptosis in GIST cells.

An international research team led by scientists at the University of Pittsburgh Cancer Institute (UPCI) discovered that by preventing cancer cells from entering a state of cellular sleep, cancer drugs are more effective, and there is a lower chance of cancer recurrence. The findings, published online in Cancer Research, are the first to show that it is possible to therapeutically target cancer cells to keep them from entering a cellular state called quiescence, or “cell sleep.” Quiescence can be a dangerous source of tumor recurrence because cancer drugs don’t typically destroy quiescent cells.

“Successful cancer therapy often is hampered by tumor cell quiescence because these cells remain viable and are a reservoir for tumor progression,” said Anette Duensing, MD, Assistant Professor of Pathology at UPCI. “By inhibiting a key regulator of quiescence, we are able to kill a larger fraction of cancer cells.”

DREAM Complex

Dr. Duensing and her colleagues made the discovery while studying gastrointestinal stromal tumors (GISTs), which are caused by a single gene mutation and can can be successfully treated with the targeted therapy drug imatinib (Gleevec). Unfortunately, GISTs rapidly develop resistance to the treatment and complete cancer remission using imatinib is rare.

A key regulator of the cancer cell sleep process is a protein complex called DREAM, which is named for the multiple proteins involved. Imatinib induces cell sleep using the DREAM complex, which means that the drug intrinsically limits its own effectiveness.

“When we disrupted the DREAM complex in the lab, we significantly increased cancer cell death using imatinib,” said Dr. Duensing. “This underscores the importance of the DREAM complex as a novel drug target worthy of preclinical and clinical investigations.”

The study is a collaboration with the Dana-Farber Cancer Institute in Boston and the Catholic University in Leuven, Belgium.

This research was supported by Research Scholar Grant RSG-08-092-01-CCG from the American Cancer Society, the GIST Cancer Research Fund, The Life Raft Group, and private donations.

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®.


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