Stopping cancer in its tracks Disrupting autophagy

https://www.sciencedaily.com/releases/2016/05/160512124918.htm

Researchers from the University of Chicago have shown that inhibiting autophagy, a self-devouring process used by cells to degrade large intra-cellular cargo, effectively blocks tumor cell migration and breast cancer metastasis in tumor models. In a study, published May 12, 2016, in the journal Cell Reports, they demonstrate that the process is essential for tumor metastasis and describe the mechanisms that connect autophagy to cell migration.

Macleod and colleagues show that if autophagy is inhibited, these metastatic tumor cells cannot move. Adhesions that don't get turned over grow larger and larger. They anchor the cell in place.

"They literally just get stuck," MacLeod said. "Through the microscope, you can see the cell wobbling, trying to move, to put out new protrusions, to migrate. But it can't, because it is stuck, unable to dissolve the adhesions at the back end of the cell. Basically, autophagy-deficient tumor cells cannot migrate and as a result cannot travel to another location. This is why we think that inhibiting autophagy could block tumor metastasis."

There are approved drugs, some now being evaluated in clinical trials, that can disrupt autophagy. One of them, hydroxychloroquine, is FDA approved to prevent and treat malaria and is currently being tested in clinical trials as a way to slow tumor growth.

Although most of these experiments in the Cell Reports paper were done with breast cancer cells transferred to mice, the researchers saw the same phenomenon in metastatic melanoma cells. "So this reliance on autophagy to metastasize appears not to be specific to any one tumor type," MacLeod said.