PSMA: a game changer in the diagnosis and treatment of advanced prostate cancer

Parsi, Meghana; Desai, Milap H; Desai, Devashish; Singhal, Sachi; Khandwala, Pushti; Potdar, Rashmika

doi:10.1007/s12032-021-01537-3

Cited by 18 publications

(10 citation statements)

References 71 publications

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“…Similarly to PSA, prostate-specific membrane antigen (PSMA) is predominantly expressed in PC cells and thus has been used as diagnostic marker and therapeutic target in clinical setting 28 . In an effort to further ensure PC cell-specific expression of perforin, we constructed anti-PSMA antibody-conjugated pLipo for their specific delivery to PC cells.…”

Section: Discussionmentioning

confidence: 99%

Gene therapy of prostate cancer using liposomes containing perforin expression vector driven by the promoter of prostate-specific antigen gene

Mizutani

Kawakami

Fujita

et al. 2022

Sci Rep

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Perforin secreted from cytotoxic lymphocytes plays a critical role in cancer immunosurveillance. The aim of this study was to investigate the therapeutic potential of liposomes containing perforin expression vector driven by the promotor of prostate-specific antigen (PSA). The anti-tumor effect of perforin was analyzed using prostate cancer (PC) PC-3 cells in which perforin expression was controlled by Tet-on system (PC-3PRF cells). Liposomes encapsulating PSA promoter-driven perforin expression vector (pLipo) were constructed for its specific expression in PC. The anti-tumor effect of pLipo was evaluated in vitro using docetaxel-resistant PC 22Rv1 PC cell line, 22Rv1DR, and PC-3 cells in the presence of human peripheral blood mono nuclear cells (PBMCs) and also in vivo using male nude mice bearing 22Rv1DR cell-derived tumor xenograft. Induction of perforin significantly inhibited growth of PC-3PRF cells. Treatment with pLipo induced perforin expression in 22Rv1DR cells expressing PSA but not in PC-3 cells lacking it. Treatment with pLipo at a low concentration was prone to inhibit growth of both cell lines and significantly inhibited growth of 22Rv1DR cells when co-incubated with PBMCs. The combined use of pLipo at a high concentration with PBMCs showed nearly complete inhibition of 22Rv1DR cell growth. Intravenous administration of pLipo via tail vein increased the level of perforin in tumor and serum and significantly decreased the tumor volume. Our results suggest that liposome-mediated PC-specific expression of perforin could be a novel therapy for advanced PC.

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Section: Discussionmentioning

confidence: 99%

Gene therapy of prostate cancer using liposomes containing perforin expression vector driven by the promoter of prostate-specific antigen gene

Mizutani

Kawakami

Fujita

et al. 2022

Sci Rep

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“…Therefore, integrating this modality into diagnostic procedures may help reduce both overdiagnosis and underdiagnosis [ 38 ]. The use of microRNAs (miRNAs) [ 39 ] and Prostate-Specific Membrane Antigen (PSMA) [ 40 ] are gaining relevance, not only for PCa diagnosis but also for therapeutic purposes. The miRNAs regulate gene expression by partially binding to their target mRNAs, resulting in the inhibition of mRNA translation or degradation of the target mRNA.…”

Section: Prostate Cancer (Pca) Diagnosismentioning

confidence: 99%

The Impact of Lifestyle on Prostate Cancer: A Road to the Discovery of New Biomarkers

Leitão

Matos

Roque

et al. 2022

JCM

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Prostate cancer (PCa) is one of the most common cancers among men, and its incidence has been rising through the years. Several risk factors have been associated with this disease and unhealthy lifestyles and inflammation were appointed as major contributors for PCa development, progression, and severity. Despite the advantages associated with the currently used diagnostic tools [prostate-specific antigen(PSA) serum levels and digital rectal examination (DRE)], the development of effective approaches for PCa diagnosis is still necessary. Finding lifestyle-associated proteins that may predict the development of PCa seems to be a promising strategy to improve PCa diagnosis. In this context, several biomarkers have been identified, including circulating biomarkers (CRP, insulin, C-peptide, TNFα-R2, adiponectin, IL-6, total PSA, free PSA, and p2PSA), urine biomarkers (PCA3, guanidine, phenylacetylglycine, and glycine), proteins expressed in exosomes (afamin, vitamin D-binding protein, and filamin A), and miRNAs expressed in prostate tissue (miRNA-21, miRNA-101, and miRNA-182). In conclusion, exploring the impact of lifestyle and inflammation on PCa development and progression may open doors to the identification of new biomarkers. The discovery of new PCa diagnostic biomarkers should contribute to reduce overdiagnosis and overtreatment.

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“…Glutamate carboxypeptidase 2, better known as prostate-specific membrane antigen (PSMA), is the approved and clinically used theranostic target in advanced prostate cancer. Radioconjugates of ligands which bind to PSMA protein overexpressed on the surface of prostate have been routinely used for tumor imaging ( 68 Ga-PSMA-11 ligand for PET/CT scanning), and, more importantly, the therapeutic 177 Lu-PSMA-617 conjugate has been recently shown to reduce death rate and prolong lives of the patients with castration-resistant prostate cancer (CRPC) in phase III clinical study (VISION) [12,13].…”

Section: The Pitchfork Proteomic Analysismentioning

confidence: 99%

“…The short cytosolic tail contains an internalization motif and interacts with various proteins enabling PSMA endocytosis [20]. The molecule is overexpressed in prostate cancer where it correlates with tumor aggressivity and vascularization and it is used as a target for radioconjugates for prostate cancer imaging (FDA approval in 2020) and recently also for therapy of advanced prostate cancer [12,13]. In addition to prostate cancer, PSMA expression has been demonstrated in several solid tumors [16][17][18][19].…”

Section: Psma-an Effective Theranostic Targetmentioning

confidence: 99%

Deep Membrane Proteome Profiling Reveals Overexpression of Prostate-Specific Membrane Antigen (PSMA) in High-Risk Human Paraganglioma and Pheochromocytoma, Suggesting New Theranostic Opportunity

et al. 2021

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Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors arising from chromaffin cells of adrenal medulla or sympathetic or parasympathetic paraganglia, respectively. To identify new therapeutic targets, we performed a detailed membrane-focused proteomic analysis of five human paraganglioma (PGL) samples. Using the Pitchfork strategy, which combines specific enrichments of glycopeptides, hydrophobic transmembrane segments, and non-glycosylated extra-membrane peptides, we identified over 1800 integral membrane proteins (IMPs). We found 45 “tumor enriched” proteins, i.e., proteins identified in all five PGLs but not found in control chromaffin tissue. Among them, 18 IMPs were predicted to be localized on the cell surface, a preferred drug targeting site, including prostate-specific membrane antigen (PSMA), a well-established target for nuclear imaging and therapy of advanced prostate cancer. Using specific antibodies, we verified PSMA expression in 22 well-characterized human PPGL samples. Compared to control chromaffin tissue, PSMA was markedly overexpressed in high-risk PPGLs belonging to the established Cluster 1, which is characterized by worse clinical outcomes, pseudohypoxia, multiplicity, recurrence, and metastasis, specifically including SDHB, VHL, and EPAS1 mutations. Using immunohistochemistry, we localized PSMA expression to tumor vasculature. Our study provides the first direct evidence of PSMA overexpression in PPGLs which could translate to therapeutic and diagnostic applications of anti-PSMA radio-conjugates in high-risk PPGLs.

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PSMA: a game changer in the diagnosis and treatment of advanced prostate cancer

Cited by 18 publications

References 71 publications

Gene therapy of prostate cancer using liposomes containing perforin expression vector driven by the promoter of prostate-specific antigen gene

Gene therapy of prostate cancer using liposomes containing perforin expression vector driven by the promoter of prostate-specific antigen gene

The Impact of Lifestyle on Prostate Cancer: A Road to the Discovery of New Biomarkers

Deep Membrane Proteome Profiling Reveals Overexpression of Prostate-Specific Membrane Antigen (PSMA) in High-Risk Human Paraganglioma and Pheochromocytoma, Suggesting New Theranostic Opportunity

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