Our second interesting abstract at ASCO 2025 was presented by first author Dr Ali Arafat, and this was a prospective biomarker study where we collected blood specimens from 100 consecutive patients who were eligible for lutetium-177, PSMA-617. The study was designed to assess the circulating tumor cell PSMA positivity and the PSMA protein detection in extracellular vesicles, also known as EVs...
Our second interesting abstract at ASCO 2025 was presented by first author Dr Ali Arafat, and this was a prospective biomarker study where we collected blood specimens from 100 consecutive patients who were eligible for lutetium-177, PSMA-617. The study was designed to assess the circulating tumor cell PSMA positivity and the PSMA protein detection in extracellular vesicles, also known as EVs. So let’s talk about the first part. At baseline, in the patient’s blood sample, those patients who had a high abundance of circulating tumor cells that expressed PSMA on their surface, in other words, PSMA positive circulating tumor cells, a higher number of those was paradoxically associated with an unfavorable overall survival to lutetium-177, PSMA-617. So more CTCs that express PSMA potentially as a measure of increased tumor burden, those patients will do worse on lutetium PSMA 617. The second thing that we did was we developed for the first time a blood-based EV proteomic analysis using a method called shotgun proteomics using mass spectrometry where we could identify in blood more than 10,000 unique EV-related proteins including PSMA and some other of our favorite cell surface targets in prostate cancer such as V7H3, Trop2, and also STEAP1. So first focusing on the EV detection of PSMA, patients that had blood-based EV high detection of PSMA at the protein level also had an inferior, worse survival to lutetium PSMA617. And interestingly enough, a number of other cell surface proteins, which are sometimes called the surface zone, also correlated with a worse survival as well. And those proteins included STEEP1, which is an energy-regulated protein, B7H3 which has been of great interest recently for multiple therapeutics and also trope 2 which has also been the target of some antibody drug conjugates so higher expression of PSMA in the blood derived from EVs associated with worse prognosis to lutetium of PSMA 617 and that worse prognosis was also found with high EV trope 2 levels, high EV steep 1 levels, and high EV B7H3 levels. In the future, we hope to be able to use a blood test to not just understand the number of circulating tumor cells, but also to quantify prostate cancer relevant proteins, including cell surface proteins in the prognosis of prostate cancer in the context of various systemic therapies. Thank you.
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