Editors' ChoiceCancer

Dangerous Liaisons: When Two Wrongs Just Might Make a Right

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Science Translational Medicine  01 May 2013:
Vol. 5, Issue 183, pp. 183ec73
DOI: 10.1126/scitranslmed.3006370

Pancreatic cancer is a physically painful disease with one of the poorest survival rates of all cancers. This is partly due to its proclivity to spread early and create metastases. Current therapies are ineffective because of the difficulty in delivering therapy specifically and thoroughly to the primary tumor and its metastases. Moreover, the pancreatic tumor stroma (or local microenvironment) often serves as a physical barrier limiting drug delivery. Quispe-Tintaya and colleagues take an unconventional approach to specifically target pancreatic metastases by administering live, attenuated radioactive bacteria.

Previous studies have suggested that the local pancreatic tumor microenvironment may have reduced immune activity compared with that of normal tissues, providing a therapeutic window to deliver bacteria specifically to tumor tissue. To accomplish this, the authors coupled 188Rhenium to a live, attenuated version of the normally pathogenic, food-borne bacteria Listeria monocytogenes. The radioactive bacteria were then delivered to a mouse model of metastatic pancreatic cancer, and the number of metastases and tumor size were measured and compared with those of controls. The authors found that the radioactive bacteria preferentially localized to metastases and significantly reduced both the number of metastases and size of the primary tumor. Importantly, they observed rapid clearance of the radioactive bacteria in normal tissues with no overt toxicity.

Indeed, vaccines derived from live, attenuated L. monocytogenes have been found to be safe in phase I clinical trials and have been exploited to express tumor antigens. The current study suggests the further possibility of harnessing this bacteria to deliver radiation and provides a clear rationale for testing the safety of this delivery method in humans. Moving forward, bacteria such as these could potentially be adapted to deliver therapies other than radiation and may be useful for targeting other tumor microenvironments with localized immune suppression. Although radiation safety issues and appropriate dosage must be optimized for use in humans, these findings provide an innovative approach to promote human health by manipulating one normally pathogenic substance (bacteria) to treat another (cancer).

W. Quispe-Tintaya et al., Nontoxic radioactive Listeriaat is a highly effective therapy against metastatic pancreatic cancer. Proc. Natl. Acad. Sci. U.S.A., published online 22 April 2013 (10.1073/pnas.1211287110). [Abstract]

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