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Abstract

Cachexia and cancer, when intertwined, precipitate severe adverse outcomes for patients, underscoring the urgent need for innovative therapeutic strategies. This dissertation addresses a significant gap in current treatments for metastatic epithelial cancers that overexpress activin A, a therapeutic target implicated in the propagation of tumorigenesis, metastatic spread, and cancer-associated cachexia. Activin A overexpression is a common denominator in various epithelial malignancies, including prostate, pancreatic, colorectal, lung, head and neck, liver cancers, and, notably, epithelial ovarian carcinoma - the focal point of this dissertation. At the heart of this research is developing and optimizing a novel lipid nanoparticle-based formulation for delivering follistatin mRNA aimed at neutralizing activin A by sequestering it in an inactive state.

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