ANDROGEN SUPPRESSION, PROSTATE-SPECIFIC MEMBRANE ANTIGEN AND THE CONCEPT OF CONDITIONALLY ENHANCED VULNERABILITY

Abstract: anti-androgen therapies represent the cornerstone of prostate cancer (pc) treatment. yet all pc patients ultimately fail efforts to rein in the androgen receptor (ar). this invention is based on the discovery that prostate-specific membrane antigen (psma), a highly pc-specific and clinically validated cell surface target, is ar-suppressed and up-regulated in pc as a result of hormonal manipulation. this up-regulation occurs in an unexpected timeframe and it occurs even in the castrate-resistant setting. as a result, hormonal therapy creates a state of conditionally enhanced vulnerability of pc to psma-targeted anti-cancer/cytotoxic agents that can be exploited by leveraging anti-ar therapy by the addition of psma-targeted agents. we demonstrate this conditionally enhanced vulnerability in a castrate-resistant animal model. the state of conditionally enhanced vulnerability may be relevant for other cancer targets and efforts to screen for them may improve other cancer therapies.

Inventor(s): Neil H. BANDER

CPC Classification: C07K16/40 (PEPTIDES (peptides in foodstuffs ; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs ; preparations for medicinal purposes ; peptides containing beta-lactam rings ; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, ; ergot alkaloids of the cyclic peptide type ; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids ; macromolecular products derived from proteins ; preparation of glue or gelatine ; single cell proteins, enzymes ; genetic engineering processes for obtaining peptides ; compositions for measuring or testing processes involving enzymes ; investigation or analysis of biological material ))

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