null New G protein inhibitor identified, with potential for cancer therapies
RI-MUHC team publishes study in Nature Communications describing a novel molecule that inhibits growth of cancer cells
Source: RI-MUHC. Published this week in Nature Communications, a new study by researchers from the Research Institute of the McGill University Health Centre (RI-MUHC) may lead to the development of new classes of drugs for cancer therapies. The study was led by Stéphane Laporte, PhD, a senior scientist in the Metabolic Disorders and Complications Program at the RI-MUHC and a professor in the Department of Medicine at McGill University. The work uncovers a new inhibitor molecule, which acts in a unique way to target small G proteins involved in cancer.
“We stumbled on this new inhibitor molecule that limits growth of cells from breast and other cancers,” says Dr. Laporte, who conducts research at the RI-MUHC’s Centre for Translational Biology.
“Interestingly, because this molecule acts specifically on the two small G proteins Ras and Arf6, which control mitogenic responses and growth factor receptor internalization, it may confer increased therapeutic advantages in different types of cancer,” says Jenna Giubilaro, a graduate student supervised by Dr. Laporte and first author of the publication.
“The inhibitor acts in a novel way on the Ras protein, which is mutated in many cancers,” adds Doris A. Schuetz, PhD, co-author and postdoctoral fellow working at the University of Montreal’s Institute for Research in Immunology and Cancer (IRIC) under the supervision of Anne Marinier, PhD. “Our findings show that this new molecule, which we named Rasarfin, will block one of the Ras regulators in order to bind to this small G protein.”
“Such discovery was unexpected,” says Dr. Laporte. “We were not looking for drugs that blocked these small G proteins, but rather ones that inhibit growth factor receptor internalization, a process that also controls hormone responses. However, this discovery will help us differentially target Ras, which has proven very challenging so far, especially when it is mutated in cancer.”
“These findings give us great hope that we can develop new classes of drugs to act on small G proteins in the treatment of triple negative breast cancer. The current standard of care is limited to conventional chemotherapy,” says Nathalie Lamarche-Vane, PhD, a collaborator on this study and a senior scientist in the Cancer Research Program at the RI-MUHC.
“This work would not have been possible without the close collaboration between RI-MUHC researchers and colleagues in Canada and Spain,” adds Dr. Laporte. These include teams led by Michel Bouvier, PhD, and Anne Marinier, PhD, at IRIC, by Audrey Claing, PhD, at the Université de Montréal, and by Jana Selent, PhD, of the Hospital del Mar Medical Research Institute (IMIM) at Pompeu Fabra University in Barcelona, Spain.
About the study:
Read the publication in Nature Communications
The authors gratefully acknowledge funding from the Canadian Institutes of Health Research.
The authors thank the Molecular Imaging and Drug Discovery technology platforms of the RI‑MUHC for services in microscopy and drug synthesis.
August 3, 2021