Colorectal cancer is the third most common cancer and the second leading cause of cancer-related death worldwide. The two most widely used drugs to treat colorectal cancer act to either inhibit enzyme activity of cancer cells or arrest tumor cell growth. But a bacterium can make them ineffective.
Researchers showed that a type of bacterium is associated with the recurrence of colorectal cancer and poor outcomes. They found that Fusobacterium nucleatum in the gut can stop chemotherapy from causing a type of cancer cell death called apoptosis.
The idea to check the role of the bacterium associated with innate immune signaling in chemotherapy resistance was linked to earlier work done by this researcher team. Their study was published in Cell in 2016. In the previous research, they studied adaptive immunity, specifically the impact of T cells on chemoresistance. They found that adaptive immunity is reversely associated with resistance of cisplatin, the drug used for ovarian cancer. This means if you have a strong T cell immunity, then the cancer cells are more sensitive to chemotherapy.
Authors found that Fusobacterium (F.) nucleatum was abundant in colorectal cancer tissues in patients with recurrence post chemotherapy, and was associated with patient clinicopathological characterisitcs.
"The results of the research were a surprise. We did not expect bacterium to contribute to chemoresistance," says the senior author.
F. nucleatum targeted TLR4 and MYD88 innate immune signaling and specific microRNAs to activate the autophagy pathway and alter colorectal cancer chemotherapeutic response.
Right now, we don't have a specific approach to selectively treat or control Fusobacterium nucleatum. Also, we don't know if an abundance of this bacterium is found in any other types of cancer chemoresistance," says the senior uthor. "Still, based on our studies, we think that if we deal with this bacterium, we may be able to delay and prevent chemoresistance in colorectal cancer."