This is more of an information-sharing exercise rather than anything I am involved in personally.
The oncology world is somewhat abuzz by the use of L. monocytogenes as an effective oncolytic against the dreaded pancreatic ductal adenocarcinoma.
The bacterium is attenuated and tagged with 188Rhenium radiologic. It appears to have 100% selectivity and specificity for PDA metastasis, but not the primary. 90% of all PDA metastasis were cleared (from mice) in two weeks time with single, weekly doses. No side effects. No toxicity. 100% selectivity for cancer cells while sparing all unaffected tissues.
One of a couple things is probably happening here. Either the tumor microenvironment is immuno-compromised, allowing the bacteria to remain and colonize the metastasis without clearance by the immune system, or the bacteria has no direct cytotoxic effects, but act solely as a highly selective vector to deploy the Rhenium payload to the metastasis. Or, lastly, perhaps L. monocytogenes has some, as of yet undiscovered, mechanism by which it is naturally drawn to PDA metastasis. Particular protein expressions? Particular gene signatures? Who's to say?
PDA is one hell of a bizarre environment, even as bizarre cancers go. Unlike every other cancer, PDA creates its own angiogenesis inhibitors, effectively shutting down blood flow to the tumor. The microenvironment is anaerobic in the extreme.
Since L. monocytogenes is an aerobic bacteria, it is logical to assume that it could not survive the hypoxic primary tumor environment as it can in the aerobic environment of the metastasis. This would explain why there is little to no effect on the primary.
Question of the day for all our oncology people:
How about using an attenuated anaerobic bacterium, perhaps a Clostridium strain, tagged with the same 188Rhenium? It would thrive in the hypoxic environment of the PDA primary.
Either way you look at it, ANYTHING that shows ANY promise or potential in a devastating malignancy like PDA (with a 5-year survival of 4%) is worth, not only investigating, but promoting like hell.
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