Vitamin A as a Treatment For Colon Cancer


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.

A Stem Cell-Based Therapy for Colon Cancer


Colorectal cancer is the third leading cause of death in the Western World. Like many other types of cancer, colorectal cancer spreads and is propagated by cancer stem cells. Therefore, understanding how to inhibit the growth of cancer stem cells provides a key to treating the cancer itself.

By inactivating a gene that drives stem cell renewal in cancer stem cells, scientists and surgeons at the Princess Margaret Cancer Centre in Toronto, Canada, have discovered a promising new approach to treating colorectal cancer.

John Dick, a senior scientist at the Princess Margaret Cancer Centre, said, “This is the first step toward clinically applying the principles of cancer stem cell biology to control cancer growth and advance the development of durable cures.”

In preclinical experiments with laboratory rodents, Dick and his team identified a gene called BMI-1 as a pivotal regulator of colon cancer stem cell proliferation. With this knowledge in hand, Dick’s laboratory dedicated many hours to finding small molecules that disarm BMI-1. Then Dick and his co-workers replicated human colorectal cancer in mice, and used their BMI-1-inhibiting small molecules to treat these cancer-stricken mice.

According to lead author of this work, Antonija Kreso: “Inhibiting a recognized regulator of self-renewal is an effective approach to control tumor growth, providing strong evidence for the clinical relevance of self-renewal as a biological process for therapeutic targeting.”

Dr. Dick explained: “When we blocked the BMI-1 pathway, the stem cells were unable to self-renew, which resulted in long-term and irreversible impairment of tumor growth. In other words, the cancer was permanently shut down.”

The clinical potential of this approach is significant, since it provides a viable treatment that specifically targets colon cancer. About 65% of all colorectal cancers have an activated BMI-1 pathway. Since physicians now have techniques for identifying the presence of BMI-1 and the tools to inhibit it, this strategy could translate into a clinical treatment that might radically transform the treatment of aggressive, advanced colorectal cancers. Such a treatment would be specific, personal, and specific. May the phase 1 trials begin soon!!!