Pre-clinical study proposes new treatment avenue for metastatic colorectal cancer

Researchers at the ONCJRI have identified a new avenue to make colorectal cancer cells more responsive to a form of targeted therapy known as BRAF inhibitors

Treatment of metastatic colorectal cancers that are driven by mutations in the gene BRAF which drives cell growth, remains a significant challenge in oncology, with patients facing grim prognoses. A recently approved combination of the drugs encorafenib and cetuximab, provided a major advance for the treatment of this difficult-to-treat cancer. However, soberingly, overall survival is only increased by 3.6 months and objective responses seen in only 20% of patients.

In a significant stride forward, a new study published in Cell Death and Disease led by Professor John Mariadason and first author Dr. Laura Jenkins from the Oncogenic Transcription Laboratory sheds light on a promising avenue to increase the effectiveness of encorafenib that works to disarm the mutant BRAF. “We discovered that colorectal cancer cells tend to respond sub-optimally to the inhibition of mutant BRAF as they have a very high threshold to the induction of cell killing by encorafenib,” said Professor Mariadason.

“This treatment resistance can be overcome by using drugs known as BH3-mimetics to lower this threshold that needs to be crossed to achieve more effective killing of the cancer cells.”

Dr. Jenkins commented, “Our findings underscore the urgency of exploring combination therapies that include the precision triggering of the cell death machinery in colorectal cancer cells”.

This research identifies a new pathway forward in the quest for more effective treatments for metastatic BRAFV600E colorectal cancers. The study’s findings pave the way for clinical investigations, offering hope for a brighter future for patients battling this aggressive form of cancer.