Targeting Mitochondrial Inhibitors for Metastatic Castrate-Resistant Prostate Cancer
Technical Report,15 Aug 2016,14 Aug 2019
Johns Hopkins University Baltimore United States
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The overarching challenge and focus area for this Partnering PI-Idea Development Award proposal is to rapidly develop novel therapeutic agents and validate these in pre-clinical studies needed to initiate clinical development of these agents for metastatic castrate resistant prostate cancer mCRPC. The hypothesis of the present proposal is that an innovative and effective therapeutic approach is possible by covalently coupling niclosamide and 7 hydroxy--Lapachone 7OH -Lap analog lipophilic mitochondria toxins MT to human serum albumin HSA via a PSA specific peptide linker sequence to systemically deliver these novel agents via the blood so that these cell penetrant MTs are restrictively released only via enzymatically active PSA within extracellular fluid ECF at sites of mCRPC. The advantage of ECF hydrolysis is that only a fraction of cancer cells need to secrete PSA since its enzymatic activity amplifies the level of liberated cell penetrant MTs within the ECF shared by all cells within the metastatic site overcoming the problem of tumor cell heterogeneity by inducing a substantial bystander effect.
- Medicine and Medical Research
- Anatomy and Physiology