Stopping cell “self-eating” may make cancer treatment more effective
By Kristina Charania
Photos by Yale Rosen
Lab research conducted by SFU associate professor Sharon Gorski suggests that cancer therapies can become more effective through the inhibition of a Pac-Man-like mechanism in eukaryotic (non-bacterial) cells. “A cell can consume parts of itself to help it survive until conditions are more favourable,” Gorski said in an interview with The Peak.
Autophagy — which literally means “self-eating” — is a basic mechanism that breaks down unwanted or unusable products generated in active cells. Vesicles act as waste containers that envelop parts of the cell’s interior cytoplasm or whole organelles during vesicle formation.
These vesicles fuse with the cell’s lysosome, which provides enzymes for the breakdown of each vesicle’s contents. “Autophagy is not simply just a degradation mechanism. It should more accurately be thought of as recycling,” Gorski explained.
The processed products are then released through pores in the lysosome and refuel the cell with necessary nutrients or participate in other cellular activities. This preserves the cell’s catabolic levels for homeostatic maintenance and allows the cell to adapt to self-stress or other environmental impositions.
Gorski’s current project examines the role of autophagy inhibition in chemotherapy treatment. The chemotherapy analyses focus on aggressive, treatment-resistant triple negative breast cancer, which has fewer treatment options than other types of cancer. In response to radiation, cells turn up autophagy in order to help the cell adapt, survive, and cope with the extra stress.
By observing breast cancer cell lines that are resistant or sensitive to chemotherapy, Gorski found that autophagy inhibition greatly increases the success of anti-cancer treatments like chemotherapy. “A lot of the time, a tumour will not respond to treatment or they will initially respond and then become resistant.
That poses a very significant clinical problem,” says Gorski. “[Autophagy inhibitor during chemotherapy] could be a particularly promising approach to treat this form of cancer.” In collaboration with SFU chemistry professor Robert Young and SFU molecular biology and biochemistry professor Steven Jones, Gorski is also testing proteins with the potential to halt autophagy in order to find the best inhibitor for the process.
Appointed as an SFU associate professor in the Faculty of Molecular Biology and Biochemistry in 2008, Gorski began researching autophagy mechanisms as part of her post-doctoral and PhD studies. She completed her bachelors of science degree in biology with honours at SFU and earned her master’s degree in genetics and PhD in developmental biology at UBC and Washington University School of Medicine, respectively. During her initial lab studies, scientific literature on autophagy was scarce. After years of attending conferences and directing research, Gorski now conducts her research at a lab in the BC Cancer Research Center. “I found [autophagy] very interesting and exciting,” Gorski notes. “And, most importantly, I saw that there was a lot of potential to further explore the process, particularly in the areas of cancer and human health.”
The senior scientist recently explained her findings at the third segment of Cafe Scientifique, entitled “Dining in: investigating cellular self-digestion for cancer therapy.” This informal discussion forum is hosted by SFU, co-sponsored by the Canadian Institutes of Health Research (CIHR), and intends to raise awareness of public health problems while linking them to research conducted by local researchers.
“It’s important that the public understands what we’re doing and why we’re trying to do it,” Gorski concludes. “Our hope is that we can make a contribution to society that will help people in the long run.”
