Gastroenterology

The researches find that the studies attempting to identify new colon cancer treatment methods found different results, a researcher at the University of Arizona Cancer Center was asked to help settle the uncertainty. Curtis Thorne, Ph.D., an assistant professor, cellular and molecular medicine, accepted the challenge and called upon one of his doctoral students, Carly R. Cabel, to assist in the project. The goal was simple: determine whether therapeutic targeting of a specific protein LRP6 is a suitable treatment strategy for colon cancer. If so; this would challenge the current scientific dogma and approaches to patient care.

New colon cancer treatment

The National Cancer Institute lists colorectal cancer (cancer in the colon or rectum); as the fourth-most common cancer diagnosed in the United States. More than 145,000 new cases are expect in 2019. A potential breakthrough to therapeutic targeting of colon cancer starts in the biology of the cancerous cells. Previously accepted research identified a protein called adenomatous polyposis coli (APC) as a tumor suppressant in the colon. When functioning properly; the APC protein prevents cells from growing and dividing too quickly or uncontrollably.

When APC is mutate and loses its function, however, the effects can be harmful. One result is abnormal activation of signaling pathways (how cells communicate with each other) that can lead to cancer. “In colon cancer, the Wnt (‘went’) pathway is use to control the proliferation of cells that line the colon,” Dr. Thorne said. “This pathway gets turned on inappropriately to where it is signaling too much. That drives colon cancer.”

The cancerous cells

In healthy gut cells, the Wnt pathway consists of a cell surface receptor, similar to an antenna, called LRP6 that “listens” to signals in the tissue environment to tell cells when to grow or when to stop growing. In cases where an APC mutation occurs, the Wnt pathway is turn on inside the cell instead of at the surface. When this happens, APC mutant cells are think to completely ignore signals coming from the LRP6 receptor.

Scientists generally believed there is little use in targeting LRP6 with therapeutics because of the “downstream” pathway triggering by APC. That was the common thinking until a team of researchers led by Ethan Lee, MD, Ph.D., at Vanderbilt University and Yashi Ahmed, MD, Ph.D., at Dartmouth College discover that Wnt receptors like LRP6 still can promote growth even when the pathway is mutat downstream at APC.

The researchers concluded targeting this protein therapeutically may be a treatment strategy to consider in blocking progression of colon cancer. Their findings are publish in the March 2018 edition of Developmental Cell, a broad-interest journal covering the areas of cell biology and developmental biology.