Toronto, ON – A discovery regarding how normal cells communicate and control their growth has been made by researchers in Dr. Anthony Pawson’s lab at the Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital. The novel findings have the potential to better inform the selection of cancer drug therapies in clinical trials, and to improve drug resistance in cancer patients.
Published in the journal Nature last week, the researchers studied a cell growth trigger that is initiated by a protein which is often mutated in cancer. This protein, called Epithelial Growth Factor Receptor (EGFR), sits on the cell surface, and sends signals inside cells to control processes such as cell survival and expansion. The protein is an important target for cancer drug therapies.
Using targeted mass spectrometry, the scientists tracked the assembly of multiple proteins into signalling complexes from the moment the epithelial growth factor receptor (EGFR) signal is turned ‘on’, to when the cell signal turns ‘off’. In cancer, the ‘off’ signal is often defective, leading to uncontrolled cell growth.
“We’ve been studying the proteins involved in this signalling pathway for over 20 years,” says Dr. Pawson, who is distinguished scientist at the Lunenfeld-Tanenbaum Research Institute and a professor of molecular genetics at the University of Toronto. “What is exciting about these findings is that they provide exquisite detail on how these proteins interact with each other and the exacting control that is placed on them to ensure accurate transmission of a growth signal.”
Dr. Pawson also holds the Apotex chair in molecular oncology at the Lunenfeld-Tanenbaum Research Institute.
The research team hopes that these findings will lead to a new class of diagnostic tests useful for large-scale clinical trials that test the effectiveness of cancer drug therapies. Currently, drugs such as Herceptin for breast cancer and Tarceva for lung cancer are limited in their effectiveness due to the generation of additional mutations in cells that lead to drug resistance, reducing the effectiveness of these drugs.
“To guide proper development and to maintain health, there are extensive controls in place to make sure that cells within the human body do not grow or divide improperly,” says Dr. Yong Zheng, a post-doctoral researcher at the Lunenfeld-Tanenbaum. “Now, we can measure all of these events right at the beginning of this crucial cell process to understand what’s going on in normal cells, so that in disease, we may quickly determine when the control systems are beginning to break down.”
The Nature paper is a result of an extensive collaboration between scientists at the Lunenfeld-Tanenbaum, researchers with Monash University in Australia, and with the mass spectrometry company AB SCIEX in Concord. The study was supported by Genome Canada through the Ontario Genomics Institute, the Ontario Research Fund from the Ontario Ministry of Research and Innovation, the Terry Fox Foundation, the Canadian Institutes of Health Research, the Canada Foundation for Innovation, and AB SCIEX.