PSMA on CTCs as a Pharmacodynamic Marker
Updated: Apr 4, 2020
06 July 2018
A week ago I shared the exciting developments surrounding the clinical development and testing of the AR-V7 test in prostate cancer. While not as big of news as before, I would like to share excitement surrounding a scientific publication that was released today. I’ll do my best to share quick context:
PSMA is a protein that is expressed on some prostate cancer cells. Brilliant chemical engineers are starting to design therapeutic agents that specifically target these proteins, and by extension, the prostate cancer cells that express these proteins. The first example of this tested in the clinic was BIND-014. The drug showed some promising activity, but was not pursued further in clinical trials due to not enough improvement in side effect profile compared to standard chemotherapy.
When we analyzed the circulating tumor cells that were in the blood of these patients before and after the received the drug, the data suggested that the agent was actually hitting the cells it intended to. With further clinical testing and validation, PSMA on circulating tumor cells might be useful as a predictive (who might benefit) and / or dynamic (is the patient benefitting now that they got the drug) biomarker for agents that target PSMA.
Safety and Efficacy of BIND-014, a Docetaxel Nanoparticle Targeting Prostate-Specific Membrane Antigen for Patients With Metastatic Castration-Resistant Prostate Cancer
Taken in the context of the entire study, it appears that PSMA might actually be a feasible drug target, that instead of a “failed drug” that BIND-014 study perhaps be a pioneering study in the space to evaluate a whole new avenue for therapeutic development for metastatic prostate cancer. I was honored to help supply data and statistical support for analyses pertaining to biomarkers as an author in this study. In general, I lament the fact that “negative” trials are not published more often, as the lessons learned from failures or near-misses can provide useful insights for the scientific and medical community. I commend JAMA Oncology for giving this study a medium for this to happen.
Improved chemical engineering techniques have been developed, and there are a few new anti-PSMA agents in early and mid-clinical development. I eagerly await the results.