Editors' ChoiceColon Cancer

Stopping Cancer in Its Tracks

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Science Translational Medicine  12 May 2010:
Vol. 2, Issue 31, pp. 31ec77
DOI: 10.1126/scitranslmed.3001255

"An ounce of prevention is worth a pound of cure." This old adage can apply to cancer in which agents that prevent cancer development, called chemoprevention, could avoid complications associated with the treatment of late-stage malignancies. It has been hard, however, to find effective chemoprevention agents with limited toxicity, and few are used in patients. Now, Zhang et al. raise hopes for chemoprevention and describe a unique approach for the prevention of colon cancer by targeting premalignant cells in colonic polyps for apoptotic cell death.

The investigators took advantage of the fact that cells in colonic polyps often harbor a loss-of-function mutation of the APC gene, an early step in forming colon. APC deficiency sensitizes these cells to apoptosis via the tumor necrosis factor–related ligand TRAIL. Short-term, intermittent cycles of treatment with TRAIL and all-trans-retinyl acetate (RAc), another agent that sensitizes cells to TRAIL, led to increased apoptotic cell death within intestinal polyps and improved survival in mice. The researchers also demonstrated that TRAIL and RAc treatment induced cell death within human colonic polyps without affecting normal tissues. Furthermore, in mouse stem cells no toxicities were observed after the long-term administration of TRAIL and RAc together.

Because currently available treatments for late-stage malignancies are often associated with toxic side effects and still produce disappointing results, finding ways to prevent cancer from developing in the first place would be a much better approach. Although the efficacy and safety of TRAIL and RAc combination therapy has yet to be evaluated in human trials, Zhang et al. have introduced a promising strategy for the prevention of colon cancer by targeting premalignant cells in colonic polyps for apoptotic cell death.

L. Zhang et al., Chemoprevention of colorectal cancer by targeting APC-deficient cells for apoptosis. Nature 464, 1058–1061 (2010). [Abstract]

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