ArticleClinical cancer research : an official journal of the American Association for Cancer Research2022
Prostate-Specific Membrane Antigen Expression and Response to DNA Damaging Agents in Prostate Cancer.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
28 citing papers in PubMed, 41 citations in OpenAlex.
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- The emerging role of prostate-specific membrane antigen-targeted radioligand therapy in metastatic hormone-sensitive prostate cancer.The oncologist · 2026Review
- Association of Prior PARP Inhibitor Exposure with Clinical Outcomes afterEuropean urology oncology · 2026Article
- Fractionation gives therapeutic benefit in animal model of [EJNMMI research · 2026Article
- Drug interactions involving therapeutic radiopharmaceuticals: a systematic review.EJNMMI radiopharmacy and chemistry · 2026Review
- Development and In Vitro Evaluation of [International journal of molecular sciences · 2025Article
- Human Kallikrein 2: A Novel Lineage-Specific Surface Target in Prostate Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- Early Detection of Prostate Cancer Using Novel ELISA-Based Biomarkers: Insights into Inflammatory and Tumor-Specific Pathways.Asian Pacific journal of cancer prevention : APJCP · 2025Article
- Targeting the tumour cell surface in advanced prostate cancer.Nature reviews. Urology · 2025Review
- Chemotherapy alters radiosensitivity and GRPR expression of prostate and breast cancer cells.EJNMMI research · 2025Article
- Synthesis of DOTA-BasedMethods and protocols · 2025Article
- Characterisation of Castration-Resistant Cell-Derived Exosomes and Their Effect on the Metastatic Phenotype.Cancers · 2025Article
- Review
- Biological determinants of PSMA expression, regulation and heterogeneity in prostate cancer.Nature reviews. Urology · 2025Review
- Immunohistochemical ERG positivity is associated with decreased PSMA expression and lower visibility in corresponding [European journal of nuclear medicine and molecular imaging · 2024Article
- Detection of tumour heterogeneity in patients with advanced, metastatic castration-resistant prostate cancer on [European journal of nuclear medicine and molecular imaging · 2024Article
- Assessment of TROP2, CEACAM5 and DLL3 in metastatic prostate cancer: Expression landscape and molecular correlates.NPJ precision oncology · 2024Article
- Exploring the role of combined external beam radiotherapy and targeted radioligand therapy with [Theranostics · 2024Article
- ASSESSMENT OF CELL SURFACE TARGETS IN METASTATIC PROSTATE CANCER: EXPRESSION LANDSCAPE AND MOLECULAR CORRELATES.Research square · 2023Article
Corrections and comments
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Authors and funding
18 authors at 2 institutions in 1 country.
Funding
Abstract
purposeProstate-specific membrane antigen (PSMA) targeting therapies such as Lutetium-177 (177Lu)-PSMA-617 are affecting outcomes from metastatic castration-resistant prostate cancer (mCRPC). However, a significant subset of patients have prostate cancer cells lacking PSMA expression, raising concerns about treatment resistance attributable at least in part to heterogeneous PSMA expression. We have previously demonstrated an association between high PSMA expression and DNA damage repair defects in mCRPC biopsies and therefore hypothesized that DNA damage upregulates PSMA expression. EXPERIMENTAL
designTo test this relationship between PSMA and DNA damage we conducted a screen of 147 anticancer agents (NCI/NIH FDA-approved anticancer "Oncology Set") and treated tumor cells with repeated ionizing irradiation.
resultsThe topoisomerase-2 inhibitors, daunorubicin and mitoxantrone, were identified from the screen to upregulate PSMA protein expression in castration-resistant LNCaP95 cells; this result was validated in vitro in LNCaP, LNCaP95, and 22Rv1 cell lines and in vivo using an mCRPC patient-derived xenograft model CP286 identified to have heterogeneous PSMA expression. As double-strand DNA break induction by topoisomerase-2 inhibitors upregulated PSMA, we next studied the impact of ionizing radiation on PSMA expression; this also upregulated PSMA protein expression in a dose-dependent fashion.
conclusionsThe results presented herein are the first, to our knowledge, to demonstrate that PSMA is upregulated in response to double-strand DNA damage by anticancer treatment. These data support the study of rational combinations that maximize the antitumor activity of PSMA-targeted therapeutic strategies by upregulating PSMA.
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Registered trials
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