PHILADELPHIA, PA (January 14, 2013)Shutting down a specific pathway in cancer cells appears to improve the ability of common drugs to wipe those cells out, according to new research from scientists at Fox Chase Cancer Center, published in the January issue of Cancer Discovery.
"Ideally, this research will eventually enable scientists to find drugs that disrupt this pathway and boost the impact of current therapies," says Igor Astsaturov, MD, PhD, Attending Physician in the Department of Medical Oncology at Fox Chase. "That's the long-term plan."
The new approach appears to enhance the tumor-killing ability of a commonly prescribed class of drugs that includes cetuximab (Erbitux), used to treat colorectal and head and neck cancers. These drugs work by blocking the activity of the epidermal growth factor receptor (EGFR), which sits on the cell surface and senses cues from the environment, telling cancer cells to grow and divide, says Astsaturov. "The whole mantra of modern day oncology is to suppress these inputs."
Although EGFR inhibitors succeed in killing cancer cells, some malignant cells still find ways to evade the drug, and become resistant to treatment. Consequently, many researchers are actively looking for ways to kill these surviving cancer cells, annihilating tumors completely.
In 2010, Astsaturov and his colleagues identified a pathway in the cell that, when blocked, completely suppressed EGFR activity. Interestingly, the pathway consists of a series of enzymes that, when working in concert, synthesize new molecules of cholesterol, an essential component of the cell wall. This pathway is particularly important to cancer cells, which are constantly dividing and therefore need to produce more cholesterol for the new cells.
Working with cancer cells in the lab, the researchers inactivated a key gene in the cholesterol synthesis pathway, and found the cells became more vulnerable to treatment with cet
|Contact: Diana Quattrone|
Fox Chase Cancer Center