One research group from Memorial Sloan Kettering Cancer Center have published their new research progress, which is a new, different strategy that kills cancer cells directly. Their study was published in Cell.

Treatment regimens for advanced colorectal cancer (CRC) involve combination chemotherapies that re toxic and largely in effective, yet have remained the backbone of therapy over the last decade. Molecularly, the vast majority of colorectal tumors contain inactivating mutations in the adenomatous coli (APC) tumor suppressor, and individuals with specific germline mutations in APC invariably develop colon cancer before the age of 35.

APC regulates a number of cellular functions, including mitosis, migration, and the maintenance of genome stability. Most importantly, APC, along with AXIN1 and GSK3β, is part of a multi-protein complex that controls output of the Wnt signaling pathway by regulating the sub-cellular localization and stability of CTNNB1, a key transcriptional regulator that deives Wnt signaling output.

In this study, researchers generated shRNA transgenic mice that enable conditional and reversible control of Apc expression by TRE-regulated, GFP-linked short-hairpin RNAs. In mice that also express a reverse tet-transactivator (rtTA), doxycycline (dox) administration drives GFP expression and Apc silencing, and subsequent dox withdrawal results in restoration of endogenous Apc expression.

Their work demonstrates a crucial role for Apc to re-establish control of crypt homeostasis in animals with hyperproliferative polyps or cancer. Collectively, their results validate the APC/WNT pathway is an attractive target for the treatment of CRC.