by Grant Goad
How do Ras-driven pancreatic cancer cells fuel their growth?
Ravenous nutrient scavengers, they do it through a process called macropinocytosis, which allows them to draw in quantities of the protein albumin. Albumin supplies the amino acids necessary for the cancer cells to grow.
Dr. Cosimo Commisso, of the Sanford Burnham Prebys Medical Discovery Institute in La Jolla, California, studies this feeding mechanism—a phenomenon whose intricacies may provide the key to new treatments for pancreatic cancer.
According to the National Cancer Institute, more than 30 percent of all cancers are driven by mutations in a family of genes called Ras. 95 percent of all pancreatic cancers and 45 percent of colorectal cancers fall into this category. In the case of pancreatic cancer, a mutation of the protein KRas drives tumor cell growth.
In macropinocytosis, a fluid-filled sac called a macropinosome breaks away from the cell membrane and is drawn into the cell’s interior, bringing with it the albumin needed to satisfy these scavengers’ high demand for nutrients.
While he was part of a team at the NYU School of Medicine, Dr. Commisso discovered that pancreatic cancer cells contain more macropinosomes than non-cancerous cells. He and his colleagues were then able to block macropinocytosis in tumor cells in mice, causing the tumors to stop growing or even contract.
Dr. Commisso says that there are two ways to harness this feeding mechanism for cancer treatment. One is to starve the tumor of nutrients by blocking the process. The other is to use macropinocytosis to deliver treatments—nanoscale therapeutics—that target the tumor cells.
Supporting Young Scientists
Fascinated by genetics and a fan since childhood of Gregor Mendel, Dr. Commisso earned his PhD in molecular and medical genetics from the University of Toronto. After studying the development of the nervous system in fruit flies, he thought it would be interesting to tie his research into disease.
Commisso did a Google search using the pathway he’d been studying and the word “cancer” as keywords. The search led him to the scientists at NYU (with whom he published an article in the journal Nature on macropinocytosis), and eventually to his own lab at Sanford Burnham.
Instrumental to his success was support from the Pancreatic Cancer Action Network’s grant program, which places heavy emphasis on attracting young researchers into the field. Commisso credits an early grant he received from the organization with opening his eyes to the need for research into this disease, which was designated a recalcitrant cancer by the National Cancer Institute as part of 2013’s Recalcitrant Cancer Research Act.
Dr. Commisso encourages other young scientists to pursue pancreatic cancer research, especially now that the need is finally receiving the wider recognition it deserves.
Read about the Pancreatic Cancer Action Network’s grant program in our recent blog post.