A new study on mice shows great promise for treating colon cancer – a simple genetic tweak can turn colorectal cancer cells into healthy tissue in a matter of days.
Anti-cancer strategies generally involve killing off tumor cells, but a group of US researchers have tried a different approach – they coaxed the cells to turn back into healthy ones by reactivating a single gene. Remarkably, in only 2 weeks, the cancer cells were gone – regaining their initial function. Six months later, there was still no sign of cancer.
“Treatment regimes for advanced colorectal cancer involve combination chemotherapies that are toxic and largely ineffective, yet have remained the backbone of therapy over the last decade,” says senior study author Scott Lowe of the Memorial Sloan Kettering Cancer Center.
The gene they reactivated is called denomatous polyposis coli (Apc), a tumor suppressor gene. Tumor suppressor genes prevent the uncontrolled growth of cells that may result in cancerous tumors. The protein made by the Apc gene plays a critical role in several cellular processes that determine whether a cell may develop into a tumor. Apc is turned off in 90% of all colorectal cancers, so researchers thought if they could turn it back up, they could eliminate cancer cells – and it worked. Furthermore, Lowe and his team managed to reactivate the gene without causing noticeable side effects.
“The concept of identifying tumor-specific driving mutations is a major focus of many laboratories around the world,” says author Lukas Dow of Weill Cornell Medical College.. “If we can define which types of mutations and changes are the critical events driving tumor growth, we will be better equipped to identify the most appropriate treatments for individual cancers.”
However, there’s a problem when it comes to implementing this treatment to humans: we can’t edit human genes the same way we edit mice genes. Researchers will have to find a way to have the same effect without actually turning on the gene.
“It is currently impractical to directly restore Apc function in patients with colorectal cancer, and past evidence suggests that completely blocking Wnt signaling would likely be severely toxic to normal intestinal cells,” said Lowe. “However, our findings suggest that small molecules aimed at modulating, but not blocking, the Wnt pathway might achieve similar effects to Apc reactivation. Further work will be critical to determine whether Wnt inhibition or similar approaches would provide long-term therapeutic value in the clinic.”
We’re still years away before this actually becomes a viable option for treatment, but there are reasons to be optimistic.
Journal Reference: Lukas E. Dow, Kevin P. O’Rourke, Janelle Simon, Darjus F. Tschaharganeh, Johan H. van Es, Hans Clevers, Scott W. Lowe. Apc Restoration Promotes Cellular Differentiation and Reestablishes Crypt Homeostasis in Colorectal Cancer. Cell, 2015; 161 (7): 1539 DOI: 10.1016/j.cell.2015.05.033
