Accession Number:

AD1048132

Title:

Targeting Mitochondrial Inhibitors for Metastatic Castrate Resistant Prostate Cancer

Descriptive Note:

Technical Report,15 Aug 2016,14 Aug 2017

Corporate Author:

Johns Hopkins University Baltimore United States

Personal Author(s):

Report Date:

2017-09-01

Pagination or Media Count:

8.0

Abstract:

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-clinicalstudies needed to initiate clinical development of these agents for metastatic castrate resistant prostate cancer mCRPC. The hypothesis of the present proposal is that aninnovative and effective therapeutic approach is possible by covalently coupling niclosamide and 7 hydroxy--Lapachone 7OH -Lap analog lipophilic mitochondria toxins MT tohuman 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 restrictivelyreleased 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 secretePSA 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 cellheterogeneity by inducing a substantial bystander effect

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Distribution Statement:

APPROVED FOR PUBLIC RELEASE