More Than Meets the Eye: Scientific Rationale behind Molecular Imaging and Therapeutic Targeting of Prostate-Specific Membrane Antigen (PSMA) in Metastatic Prostate Cancer and Beyond

Prostate cancer is the second most common cancer type in men globally. Although the prognosis for localized prostate cancer is good, no curative treatments are available for metastatic disease. Better diagnostic methods could help target therapies and improve the outcome. Prostate-specific membrane...

Full description

Bibliographic Details
Main Authors: Anniina Hyväkkä, Verneri Virtanen, Jukka Kemppainen, Tove J. Grönroos, Heikki Minn, Maria Sundvall
Format: Article
Language:English
Published: MDPI AG 2021-05-01
Series:Cancers
Subjects:
Online Access:https://www.mdpi.com/2072-6694/13/9/2244
_version_ 1797535015909720064
author Anniina Hyväkkä
Verneri Virtanen
Jukka Kemppainen
Tove J. Grönroos
Heikki Minn
Maria Sundvall
author_facet Anniina Hyväkkä
Verneri Virtanen
Jukka Kemppainen
Tove J. Grönroos
Heikki Minn
Maria Sundvall
author_sort Anniina Hyväkkä
collection DOAJ
description Prostate cancer is the second most common cancer type in men globally. Although the prognosis for localized prostate cancer is good, no curative treatments are available for metastatic disease. Better diagnostic methods could help target therapies and improve the outcome. Prostate-specific membrane antigen (PSMA) is a transmembrane glycoprotein that is overexpressed on malignant prostate tumor cells and correlates with the aggressiveness of the disease. PSMA is a clinically validated target for positron emission tomography (PET) imaging-based diagnostics in prostate cancer, and during recent years several therapeutics have been developed based on PSMA expression and activity. The expression of PSMA in prostate cancer can be very heterogeneous and some metastases are negative for PSMA. Determinants that dictate clinical responses to PSMA-targeting therapeutics are not well known. Moreover, it is not clear how to manipulate PSMA expression for therapeutic purposes and develop rational treatment combinations. A deeper understanding of the biology behind the use of PSMA would help the development of theranostics with radiolabeled compounds and other PSMA-based therapeutic approaches. Along with PSMA several other targets have also been evaluated or are currently under investigation in preclinical or clinical settings in prostate cancer. Here we critically elaborate the biology and scientific rationale behind the use of PSMA and other targets in the detection and therapeutic targeting of metastatic prostate cancer.
first_indexed 2024-03-10T11:38:37Z
format Article
id doaj.art-7320b827af894b30b132ff55282e8551
institution Directory Open Access Journal
issn 2072-6694
language English
last_indexed 2024-03-10T11:38:37Z
publishDate 2021-05-01
publisher MDPI AG
record_format Article
series Cancers
spelling doaj.art-7320b827af894b30b132ff55282e85512023-11-21T18:40:30ZengMDPI AGCancers2072-66942021-05-01139224410.3390/cancers13092244More Than Meets the Eye: Scientific Rationale behind Molecular Imaging and Therapeutic Targeting of Prostate-Specific Membrane Antigen (PSMA) in Metastatic Prostate Cancer and BeyondAnniina Hyväkkä0Verneri Virtanen1Jukka Kemppainen2Tove J. Grönroos3Heikki Minn4Maria Sundvall5Institute of Biomedicine, Cancer Research Unit, FICAN West Cancer Center Laboratory, University of Turku and Turku University Hospital, FI-20520 Turku, FinlandInstitute of Biomedicine, Cancer Research Unit, FICAN West Cancer Center Laboratory, University of Turku and Turku University Hospital, FI-20520 Turku, FinlandTurku PET Centre, University of Turku, FI-20521 Turku, FinlandPreclinical Imaging Laboratory, Turku PET Centre, University of Turku, FI-20520 Turku, FinlandDepartment of Oncology, FICAN West Cancer Center, University of Turku and Turku University Hospital, FI-20521 Turku, FinlandInstitute of Biomedicine, Cancer Research Unit, FICAN West Cancer Center Laboratory, University of Turku and Turku University Hospital, FI-20520 Turku, FinlandProstate cancer is the second most common cancer type in men globally. Although the prognosis for localized prostate cancer is good, no curative treatments are available for metastatic disease. Better diagnostic methods could help target therapies and improve the outcome. Prostate-specific membrane antigen (PSMA) is a transmembrane glycoprotein that is overexpressed on malignant prostate tumor cells and correlates with the aggressiveness of the disease. PSMA is a clinically validated target for positron emission tomography (PET) imaging-based diagnostics in prostate cancer, and during recent years several therapeutics have been developed based on PSMA expression and activity. The expression of PSMA in prostate cancer can be very heterogeneous and some metastases are negative for PSMA. Determinants that dictate clinical responses to PSMA-targeting therapeutics are not well known. Moreover, it is not clear how to manipulate PSMA expression for therapeutic purposes and develop rational treatment combinations. A deeper understanding of the biology behind the use of PSMA would help the development of theranostics with radiolabeled compounds and other PSMA-based therapeutic approaches. Along with PSMA several other targets have also been evaluated or are currently under investigation in preclinical or clinical settings in prostate cancer. Here we critically elaborate the biology and scientific rationale behind the use of PSMA and other targets in the detection and therapeutic targeting of metastatic prostate cancer.https://www.mdpi.com/2072-6694/13/9/2244castration resistant prostate cancer (CRPC)molecular imagingpositron emission tomography (PET)prostate-specific membrane antigen (PSMA)radionuclide therapytherapeutic antibodies
spellingShingle Anniina Hyväkkä
Verneri Virtanen
Jukka Kemppainen
Tove J. Grönroos
Heikki Minn
Maria Sundvall
More Than Meets the Eye: Scientific Rationale behind Molecular Imaging and Therapeutic Targeting of Prostate-Specific Membrane Antigen (PSMA) in Metastatic Prostate Cancer and Beyond
Cancers
castration resistant prostate cancer (CRPC)
molecular imaging
positron emission tomography (PET)
prostate-specific membrane antigen (PSMA)
radionuclide therapy
therapeutic antibodies
title More Than Meets the Eye: Scientific Rationale behind Molecular Imaging and Therapeutic Targeting of Prostate-Specific Membrane Antigen (PSMA) in Metastatic Prostate Cancer and Beyond
title_full More Than Meets the Eye: Scientific Rationale behind Molecular Imaging and Therapeutic Targeting of Prostate-Specific Membrane Antigen (PSMA) in Metastatic Prostate Cancer and Beyond
title_fullStr More Than Meets the Eye: Scientific Rationale behind Molecular Imaging and Therapeutic Targeting of Prostate-Specific Membrane Antigen (PSMA) in Metastatic Prostate Cancer and Beyond
title_full_unstemmed More Than Meets the Eye: Scientific Rationale behind Molecular Imaging and Therapeutic Targeting of Prostate-Specific Membrane Antigen (PSMA) in Metastatic Prostate Cancer and Beyond
title_short More Than Meets the Eye: Scientific Rationale behind Molecular Imaging and Therapeutic Targeting of Prostate-Specific Membrane Antigen (PSMA) in Metastatic Prostate Cancer and Beyond
title_sort more than meets the eye scientific rationale behind molecular imaging and therapeutic targeting of prostate specific membrane antigen psma in metastatic prostate cancer and beyond
topic castration resistant prostate cancer (CRPC)
molecular imaging
positron emission tomography (PET)
prostate-specific membrane antigen (PSMA)
radionuclide therapy
therapeutic antibodies
url https://www.mdpi.com/2072-6694/13/9/2244
work_keys_str_mv AT anniinahyvakka morethanmeetstheeyescientificrationalebehindmolecularimagingandtherapeutictargetingofprostatespecificmembraneantigenpsmainmetastaticprostatecancerandbeyond
AT vernerivirtanen morethanmeetstheeyescientificrationalebehindmolecularimagingandtherapeutictargetingofprostatespecificmembraneantigenpsmainmetastaticprostatecancerandbeyond
AT jukkakemppainen morethanmeetstheeyescientificrationalebehindmolecularimagingandtherapeutictargetingofprostatespecificmembraneantigenpsmainmetastaticprostatecancerandbeyond
AT tovejgronroos morethanmeetstheeyescientificrationalebehindmolecularimagingandtherapeutictargetingofprostatespecificmembraneantigenpsmainmetastaticprostatecancerandbeyond
AT heikkiminn morethanmeetstheeyescientificrationalebehindmolecularimagingandtherapeutictargetingofprostatespecificmembraneantigenpsmainmetastaticprostatecancerandbeyond
AT mariasundvall morethanmeetstheeyescientificrationalebehindmolecularimagingandtherapeutictargetingofprostatespecificmembraneantigenpsmainmetastaticprostatecancerandbeyond