What is it about?

In this study we have used a protein engineering strategy to hijack the complex anthrax toxin mechanism to deliver a potent anti-tumor toxin by leveraging overactive membrane serine proteases found on the surface of ovarian cancer cells. PAS:LF is a potent tumor-selective inactivator of MAPK cell signaling pathways that promote tumor cell survival. Using several preclinical mouse models, we show that tumor growth is halted following treatment with PAS:LF and is well-tolerated with no off-target adverse side effects. The drug effectively kills a broad range of patient derived ovarian tumors and might represent a new therapeutic strategy for cancer treatment.

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Why is it important?

Ovarian cancer is the most lethal gynecological malignancy. There is a significant unmet need for more effective targeted therapies. We have developed a promising approach for treating women with late-stage and recurrent ovarian cancers, utilizing a mechanism distinct from anti-cancer chemotherapeutic agents.

Perspectives

Cancer is a terrible disease and too often deadly. I hope this article will bring a new perspective to utilizing proteases in anti-cancer therapies.

Toni Antalis
University of Maryland Baltimore

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This page is a summary of: Selective targeting of metastatic ovarian cancer using an engineered anthrax prodrug activated by membrane-anchored serine proteases, Proceedings of the National Academy of Sciences, July 2022, Proceedings of the National Academy of Sciences, DOI: 10.1073/pnas.2201423119.
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