A new study that was published in the journal Cancer Cell, has introduced a way to treat colon, which is not only a leading cause of cancer deaths worldwide, but is notoriously resistant to treatment.
This collaboration between Swiss and Japanese scientists has identified an anticancer mechanism that includes vitamin A that can be tapped to inhibit colon cancer.
Colon cancer patients are typically treated with chemotherapy, which kills off most of the cancer cells, but leaves a few resistant cells that then aggressively grow back to form another deadlier tumor that can readily spread throughout the body. Chemotherapy ultimately fails because there are a core of rouge stem cells that divide uncontrollably called cancer stem cells that drives the growth of the cancer. These cancer stem cells are what is driving the growth of the tumor and if these cancer stem cells are not eliminated, the tumor will simply come back after chemotherapy. When a colon cancer patient receives treatment such as chemotherapy, most of the cancer cells die off.
Joerg Huelsken, Ph.D., of Ecole Polytechnique Federale de Lausanne (EPFL) led his research team to understand how stem cells populations in the colon give rise to new colon cells to replace dead, dying or cells that have been sloughed off. In mice and in tissue samples from human patients, a protein called HOXA5 kept asserting itself. HOXA5 turns out to be an integral part of the machinery of the cell that ensures that the cells of the colon properly differentiate after they are born from colon stem cells.
Huelsken’s team showed that in the colon, HOXA5 helps restrict the number of stem cells. Cancerous stem cells, however, block the expression of HOXA5 and prevent it from restricting stem cell numbers. HOXA5 is part of a signaling pathway that activates aspects of the cellular machinery that negatively controls cell growth. By blocking expression of the HOXA5 gene, these cancerous stem cells in the colon can grow uncontrollably and spread, thereby causing relapses and metastasis or spread of the colon cancer.
Huelsken and his team, in collaboration with Japanese researchers from Kyoto University investigated ways to unblock the expression of HOXA5 in colon cancer stem cells. The answer came from an unexpected corner – vitamin A. Vitamin A is a member of the retinoid family of molecules and has been known for some time to be able to induce differentiation of skin-based stem cells. Huelsken’s group showed that retinoids like vitamin A can upregulate HOXA5 and antagonize the mechanism in colon cancer stem cells that staunch its expression.
In a mouse colon cancer model system, treatment with retinoids not only blocked progression of the tumors, but normalized the tissue. The activation of the expression of the HOXA5 gene eliminated cancer stem cells and prevented metastasis in live animals. These results were then faithfully recapitulated in samples from actual patients.
From this study, it seems that screening tumors for the absence of HOXA5 expression is a relatively easy way to determine if a patient’s colon cancer will respond to treatment with vitamin A. Treatment with vitamin A or other retinoids might not only prove effective against colon cancer, but also as a preventive measure in high-risk patients.