Quiescent cancer cells potential target for colorectal cancer therapy
For patients with colorectal cancer the tumour often recurs since quiescent cancer cells can escape therapy and start growing again. In a study from IGP, the researchers have discovered a protein that identifies such quiescent cancer cells. This could improve the possibilities to eliminate also these cells and ultimately lead to more effective therapy.
Colorectal cancer is the third most common cancer in the world and it ranks second in mortality. Therapy most often consists of surgery, followed by chemotherapy or radiation, but unfortunately it is common that the cancer recurs after therapy is completed.
The reason for this is the most clinically used therapies target cells that are proliferating by dividing rapidly, which is a classic feature of cancer cells. However, the tumour can also contain quiescent cancer cells, that are not dividing. These cells can transform into proliferating cancer cells, leading to recurrence and eventual metastasis. Thus, targeting and eliminating the quiescent cancer cells is necessary to effectively treat the tumour.
In the study from IGP, the researchers used a cell model of colorectal cancer to identify proliferating and quiescent cancer cells. They also discovered the protein ATF3 as a novel signature of quiescent cancer cells.
“We found that the gene encoding ATF3 was much more active in the quiescent cells as compared to proliferating cells. It seems like ATF3 is required for the cells to remain quiescent. We also saw that cancer cells lacking ATF3 were more sensitive to anticancer agents,” says Xiaonan Zhang, researcher at IGP, who led the study.
The results suggested that lowering ATF3 could improve the efficacy of drugs targeting the proliferating cancer cells. To test this the researchers treated the cancer cells with a combination of the chemotherapeutic drug 5-FU and substances that reduced the amount of ATF3.
“In our cell model we found that the combination treatment was more effective than when the cells were exposed to only 5-FU. We think that a novel treatment strategy could be to combine conventional drugs that eliminate proliferating cells with targeting quiescent cancer cells by reducing ATF3 levels. This could ultimately lead to long lasting remissions and improved survival of cancer patients”, says Xiaonan Zhang.
The study has been published in the journal Cell Death and Disease.
Länkar
The paper in Cell Death and Disease
Xiaonan Zhang's research in Tobias Sjöblom's group