Can Cancer Development Be Reversed? Repairing a Damaged Gene!

Large bowel (colon-rectum) cancers are the third most common cancer and rank second among cancers resulting in death. Molecular examination reveals an inactivating mutation in the tumor suppressor gene called adenomatous polyposis coli (APC) in most colorectal cancers (%80-%90). The study discussed in this article has shown that repairing this gene may make it possible to transform cancer cells into normal cells.

The APC protein; regulates many cellular functions, including cell division, cell migration, and maintenance of genetic information stability. Suppression of APC function, which has vital roles in cells, is considered an initiating event in colorectal cancer. Molecular investigations have shown genetic changes (mutations) that inactivate the APC tumor suppressor in the vast majority of colorectal tumors. APC-mutant colorectal cancers cause more than 600,000 deaths worldwide each year. Therefore, developing strategies that could reactivate the APC tumor suppressor has become a notable subject of clinical investigation.

Mice were tested in the first stage of the study conducted by Dow and colleagues and published in the journal Cell. In their mouse study, adenomas arising after APC was rendered nonfunctional exhibited tissue and molecular characteristics similar to familial and spontaneously occurring APC-mutant human adenomas and colorectal cancers. This similarity made the study a tool for investigating cancer in humans.

In the same study, restoring the function of intracellular APC protein was observed to cause regression of polyp growth in the mouse intestine. It was also shown that repairing APC protein not only targeted differentiation in colorectal polyps but also reversed growth toward cancer development.

As in many cancers, colorectal cancers contain not only defects in the APC protein but also mutations in the proto-oncogene KRAS and tumor suppressor TP53, which cooperate in tumor progression and the maintenance of cancer development. Dysfunction of these proteins triggers tumor development. Based on this knowledge, the study also investigated the effect of repairing APC protein on tumor progression in KRAS- and p53-mutant mice. It showed that the functionality of the Wnt pathway regulated by APC protein caused disease regression and restored tissue homeostasis. (homeostasis: maintaining the organism's internal environment at a constant level with the help of regulatory systems to sustain life)

In conclusion, the study findings indicate that repairing the tumor suppressor mechanism in cells, in which APC protein plays an important role, may reverse colorectal cancer development. These findings shed light on the possibility of developing alternative treatments by targeting APC protein in colorectal cancers.