Based on a new research, carried out at the University of Michigan Rogel Cancer Center, cancer stem cells exist in more than one state and are very plastic, meaning they can change form, sliding back and forth between a dormant state and a rapidly growing state. This plasticity is responsible for cancer’s two key characteristics: multiplying and spreading, Michigan Medicine University of Michigan reports.
“When we use targeted therapies, they often only work for a certain period of time, and then the cancer becomes resistant. A lot of that resistance is from the cancer stem cells. They change form to evade the targeted therapy,” says Wicha, Madeline and Sidney Forbes professor of oncology and director of the Forbes Institute for Cancer Discovery at the Rogel Cancer Center.
It turns out the cell metabolism controls this change, suggesting a possible way in to attack the stem cells. Cells get energy through mitochondria, which depends on oxygen, and through sugar, or glucose. Cancer stem cells pull energy both ways. In the dormant state, the cells use glucose; in the proliferative state, they depend on oxygen.
So researchers attacked the metabolism in both ways. They used a drug currently used to treat arthritis that’s known to block mitochondria, and they manipulated glucose to block that path. They tested this in mice with breast cancer and found they could knock out the stem cells. Results are published in Cell Metabolism.
“Rather than just try to use toxic chemicals to kill a cell, we use the metabolism of the cell itself to kill the cancer,” Wicha says.
Researchers are also understanding that the immune system is regulated by metabolism, suggesting the possibility of combining anti-stem cell therapies with immunotherapies.
