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PEER-TO-PEER CLINICAL CONVERSATIONS |
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Beyond PSMA - New Targets in Prostate Cancer
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Tanya B. Dorff, MD
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| Tanya Dorff joins Alicia Morgans to discuss the highlights from her presentation at the 2022 GU ASCO Annual meeting focusing on new targets in prostate cancer beyond prostate-specific membrane antigen (PSMA). She highlights potential new targets including prostate stem cell antigen (PSCA), JNJ-75229414 is a KLK2 CAR T, and STEAP-1. Drs. Morgans and Dorff also discuss tumor heterogeneity and neuroendocrine disease.
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| CAR T and Cellular-Based Therapies |
Alicia Morgans, MD, MPH, and Vivek Narayan, MD, MS
Vivek Narayan joins Alicia Morgans to discuss his work with CAR T-cell therapies and prostate cancer, the first-in-human study. Using a low-dose escalation approach, Dr. Narayan and his team designed the study safety as the primary objective to evaluate the feasibility of manufacturing and delivering the CAR T-cells. |
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| Beyond Prostate-Specific Membrane Antigen: New Targets in Prostate Cancer |
| Tanya B. Dorff, MD |
| Tanya Dorff discusses new targets in prostate cancer beyond prostate-specific membrane antigen (PSMA). Dr. Dorff notes that when defining expression potential targets, it is important to know how we measure expression and assess how much expression is enough. We must understand efficacy/toxicity differences with different approaches (BiTE vs CAR T vs antibody drug conjugate/radiopharmaceutical) to the same antigen. |
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| Biomarker Testing in the Era of Novel Therapeutics |
| Himisha Beltran, MD
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| Himisha Beltran discusses biomarker testing in the era of novel therapeutics. Dr. Beltran notes that, as we saw in the TheraP trial, not all patients with PSMA-positive disease identified by PET respond to PSMA-directed therapy. Furthermore, approximately 15-20% of patients with late-stage castration-resistant prostate cancer have PSMA-low or PSMA-negative disease. There are several important aspects to patient selection for PSMA-directed therapy, including: (i) expression of the target (PSMA), (ii) other biomarkers of response (tumor features, drug features, and drug mechanism), and (iii) mechanisms of disease resistance (to guide next therapy).
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| Mechanisms of Resistance to Radiopharmaceuticals |
| Johannes Czernin, MD |
| The 2022 GU ASCO Annual meeting included a session on novel treatment implementation focusing on PSMA targeting and beyond, with a presentation by Dr. Johannes Czernin discussing mechanisms of resistance to radiopharmaceuticals. |
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| Targeting Prostate-Specific Membrane Antigen: Lutetium and the Next Wave of Novel Radiopharmaceuticals
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| Shahneen Sandhu, MD, Ph.D., MBBS, FRACP
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| Shahneen Sandhu discusses targeting prostate-specific membrane antigen (PSMA), specifically lutetium and the next wave of novel radiopharmaceuticals. Dr. Sandhu notes that PSMA is a glutamate carboxypeptidase II transmembrane protein that has a pro-proliferative function by activating PI3K and AKT/mTOR pathways via glutamate cleavage. High cellular PSMA expression is associated with poorer patient outcomes and is prevalent in castration resistance. PSMA theranostics combines the diagnostic companion of 68Ga-PSMA-11 PET/CT with the targeted therapeutic of 177Lu-PSMA-617 therapy.
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| Future Targets for Cellular Therapy in Prostate Cancer |
| Vivek Narayan, MD, MS |
| Vivek Narayan discusses some of the barriers to the efficacy of CAR-T therapies. These include limited T-cell expansion or persistence once infused, dysfunction of infused T-cells, tumor immune escape by down-regulation of the targeted tumor antigen, and inflammatory toxicities such as CRS or neurotoxicity. |
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