Colorectal cancer rates have declined in the past few decades, but still remain a common cause of death between men and women in the United States. Fortunately, more therapies to help the cancer community may be on their way. A new study from the Boston University School of Medicine has developed a novel colorectal cancer inhibitor that could prevent tumors from growing and spreading throughout the body.
The Wnt/β-catenin signaling pathway is critical for many cellular functions that help colorectal cancer tumors grow. Β-catenin by itself helps with tumor initiation, progression, and metastasis. Wnt pathway inhibitors have had limited success in blocking β-catenin activity, and their effect has only been so far in animal models.
In the current study, the research team created an anti-cancer compound called Factor Quinolinone Inhibitors (FQIs). The goal of these compounds is to stop a protein known as LSF that helps with many biological processes. It will also prevent cancer cells from DNA-binding, partner protein-binding, and other transactivation activities. They did observe a positive correlation between LSF expression and activation of Wnt in colorectal cancer cells.
“Given the critical role of Wnt signaling in CRC tumorigenesis, we set out to examine the effect of FQIs on CRC tumor growth and found we could successfully establish the significant results of LSF inhibition in the suppressed tumor growth,” says co-author Dr. Vipul Chitalia, an associate professor of medicine at Boston University School of Medicine, in a statement.
The researchers studied the effectiveness of FQI in inhibiting the LSF protein using both experimental models and cell cultures. By reducing the activity in the Wnt signaling pathway, the FQI treatment slowed down colorectal tumor growth.
The researchers suggest the findings show how changing even the transcriptional levels of a cell can cause a massive ripple effect — in this case, suppressing colorectal cancer tumor growth and increasing the odds for better treatment outcomes. “Such interplay of cancer pathology needs to be better defined to understand the drivers of heightened risk of tumor growth in CRC patients,” says lead author Dr. Saran Lotfollahzadeh, a post-doctoral research fellow at Boston University School of Medicine.
The study is published and available to read in the American Journal of Pathology.