Princess Margaret Cancer Centre Innovation Acceleration Fund Announces 1st Round of 2018 Awards to Researchers to Develop Early Stage Technologies
Generation of inhibitors targeting general control nonderepressible 2 (GCN2) as a novel targeted therapy for ovarian cancer
Drs. Tracy McGaha and Robert Rottapel, Senior Scientists at UHN’s Princess Margaret Cancer Centre, along with their teams were awarded funding to support the discovery and development of small molecule inhibitors of GCN2 as a novel therapeutic mechanism for targeted therapy of ovarian cancer.
Ovarian cancer is the leading cause of death from gynecologic cancer in Canada with a 5-year survival of only 44%, underscoring the need for novel treatment strategies beyond conventional chemotherapy alone. GCN2 is a key factor that controls the cellular stress response in conditions of low amino acid availability; the McGaha/Rottapel team has identified GCN2 as a key contributor to suppression of inflammatory anti-tumor activities of the immune system. Further, they have demonstrated that ovarian cancer tumor cells exhibit a molecular GCN2 dependency for tumor growth in vivo and for resistance towards Platinum based chemotherapeutics. Together, these findings suggest that targeting GCN2 may represent a novel therapeutic approach towards ovarian cancer that enlists both modulation of the immune system and tumor intrinsic dependencies.
The studies conducted by Drs. McGaha and Rottapel using laboratory models of ovarian cancer have shed light on the multiple molecular and cellular mechanisms by which GCN2 drives disease pathogenesis. The $250,000 in IAF funding awarded will be used to build upon these findings to develop new GCN2 inhibitors for the treatment of ovarian cancer. Say Drs. McGaha and Rottapel, “Targeted therapies have transformed the ways in which we treat many forms cancer, improving patient outcomes with fewer adverse side effects. This project aims to develop a new drug against a key factor driving ovarian cancers, with the potential to improve therapeutic efficacy and safety in this patient population of high unmet need.”
Artificial Intelligence-enabled automated pathology annotation and decision support tool
Dr. Phedias Diamandis, an Affiliate Scientist at UHN’s Princess Margaret Cancer Centre was awarded $250,000 by the IAF to further his work in the development of a novel automated pathology software platform that utilizes artificial intelligence and machine learning to aid in decision support for physicians.
Morphologic classification of disease by pathologists remains a valuable, timely and cost-effective diagnostic tool. It also provides an important means for triaging samples for molecular testing that will help guide therapeutic decision-making. However, it is prone to inter-observer variability and can lead to errors in pathology diagnoses. In fact, it is estimated that significant errors affect ~1% of patients, or about 10,000 patients/million. In an effort to modernize and improve the microscopic exam, Dr. Diamandis is developing an automated decision support tool coined “brAIn”: “biological rendering through Artificial Intelligence and neural networks”. Dr. Diamandis believes that brAIn will improve patient care through quality assurance and error prevention, and improve efficiency through a reduction in diagnostic turnaround time and cost.
The IAF funding awarded will be used to further enhance, develop, and test the brAIn software in order to provide clinical validation for the benefits it can provide to patients, physicians, and hospitals. As Dr. Diamandis summarizes, "Artificial intelligence is a powerful and transformative tool that will likely be adopted in all aspects of cancer research and care. It is, however, largely untested. The IAF is helping us bring our tool to a level where we begin carrying out important large-scale validation studies. This is what's needed to help bring the technology to a point where it is safe and useful for patient care."