EGF yellow colour binds to the surface of a human breast cancer cell, enters into the cytoplasm, then tracks to the cell nucleus, where the radioactive particles damage the DNA, killing the cell. |
Toronto scientists are taking a page from Greek legend by employing a Trojan Horse technique that may treat breast cancer proven resistant to chemotherapy.
A study in the September Journal of Nuclear Medicine found that a drug that combines a radioactive isotope called Indium-111 with an amino acid called epidermal growth factor (EGF) slowed the growth of large tumours three-fold and caused tiny tumours to regress when injected into mice.
"Like the legend of the Trojan Horse in which invading soldiers hid inside a hollow wooden horse to fool the enemy, this drug enables deadly radioisotopes to hide within the EGF as it passes naturally into the breast cancer cells," says senior author Professor Raymond Reilly of the University of Toronto's Leslie Dan Faculty of Pharmacy and Toronto General Hospital, University Health Network. "These radioisotopes cannot harm the cancer cell from the outside. The key is getting them into the cancer cell where their radioactive particles can destroy the cell's DNA."
The normal role of EGF is to bind to receptors on the surface of certain cells, including some breast cancer cells, to stimulate their growth. EGF later moves inside the cell to shut off the growth signal. Working on the theory that EGF can also transport other substances, the scientists created a drug - 111In-hEGF - that mixes EGF with the radioactive isotope Indium-111. Once injected into the body, the EGF portion carries the Indium-111 to the heart of the cancer cell. Breast cancer cells are especially susceptible to this drug because they use more EGF than normal cells, says Reilly, the study's senior author. Toronto General research technologist Paul Chen is the first author of the study, which received funding from the U.S. Army Breast Cancer Research Program and the Susan G. Komen Breast Cancer Foundation.
A team led by radiation and medical biophysics professor Dr. Katherine Vallis, a radiation oncologist at Princess Margaret Hospital, is launching the first phase of a clinical trial to test the safety of 111In-hEGF in patients with advanced, chemotherapy-resistant breast cancer. For more information on the trial, call 416-946-2121.
CONTACT: Professor Raymond Reilly, Leslie Dan Faculty of Pharmacy, 416-946-5522, raymond.reilly@utoronto.ca or Jessica Whiteside, U of T public affairs, 416-978-5948, jessica.whiteside@utoronto.ca
Journal
Journal of Nuclear Medicine