Cancer is one of the leading causes of death worldwide, colon cancer, is known to be resistant to treatment. It is known that there are many reasons why this cancer is so elusive to treatment, but one of them, very important, has to do with the resilience of a particular group of cancer cells in the colon that are responsible for relapses. Unfortunately most conventional therapies are largely ineffective. A group of researchers from the EPFL in Switzerland have now identified a biological mechanism that could be used to prevent the recurrence of colon cancer. The new approach is based on the activation of a protein that is ‘lost’ in this group of resistant tumor cells. The researchers, whose work is published in “Cancer Cell” have been able to reactivate it using vitamin A, which kills cancer cells and prevents metastasis. The study thus proposes a new way to treat colon cancer: Vitamin A.
When a patient with colon cancer treated, most cancer cells die. However, genetic mutations caused the cancer at the beginning can survive in a specific group of cells in the colon. These are stem cells, which means, that the cells are normal cells that manufacture the colon. And when treatment is finished, the surviving stem cells, which still have cancer mutations can recur and cause a relapse.
What we have now made Huelsken Joerg laboratory to study these differentiated colon cells originating from stem cells of the intestine. Using a variety of different techniques, the team studied cells, mouse models and human patient samples.
The researchers focused on a protein called HOXA5, which belongs to a family of proteins that regulate the development of the fetus. Such proteins are produced during early development and work together to ensure that all tissues are correctly identified and that the body and limbs of the fetus are modeled accordingly. In the body of an adult, HOXA5 proteins are responsible for regulating the body’s stem cells to maintain both the identity and function of different tissues. Huelsken team has found that in the intestine HOXA5 plays an important role in limiting the number of stem cells and cells that form them.
Like other proteins, HOXA5 originates from a specific gene. The new study shows that colon cancer stem cells using a biological mechanism that blocks the gene (this mechanism is called ‘signaling pathway’). The purpose of signaling pathway is transmitting biological information from one area to another, for example, the outer membrane to the cell nucleus. Thus, by blocking HOXA5 gene, the colon cancer stem cells can grow uncontrollably and spread, causing metastases and relapses.
The researchers looked for ways to reverse blocking HOXA5. They found the response in vitamin A. This small chemical structure called retinoid and is known to induce the differentiation of stem cells of the skin. Scientists have found what can reactivate HOXA5.
In mice with colon cancer, treatment with retinoids blocked tumor progression and tissue normalized. And when they activated the gene, they eliminated the cancer stem cells and prevented metastasis in animals. The researchers also obtained similar results with real patient samples.
The new study suggests that patients who could benefit from this treatment can be identified based on their expression pattern for gene HOXA5. Researchers believe that differentiation therapy with retinoids could be significantly effective against colon cancer, not only for the treatment of existing disease, but also as a preventive measure in high-risk patients.