Development of a Biologic Basis for PSMA Targeting in Prostate Cancer
Abstract
PSMA is a membrane protein that is highly expressed in the prostate and prostate cancers. It is also strongly expressed in the neovasculature of most solid tumors. PSMA is therefore an excellent target for therapy. We have examined the biology of PSMA relative to ;he possibility of it serving as a target for prodrug or targeted small molecule therapeutics. We observe that although PSMA can hydrolyze glutamate from polygammglutamated methotrexate, that not all antifolate serve as substrates that can have their antitumor activity enhanced by PSMA. We have also observed that other forms of PSMA such as PSM' and PSMA-like proteins, lack folate hydrolase activity and thus will not interfere with the prodrug activities of PSMA. Ligands that bind with high affinity to PSMA may have activity as imaging agents, but we have not observed that ligands increase the rate of internalization of PSMA and thus targeted toxins need to be designed that do not need to be internalized for their antitumor activity to be expressed.
Document Details
- Document Type
- Technical Report
- Publication Date
- Feb 01, 2004
- Accession Number
- ADA423232
Entities
People
- Warren Heston