Metastatic Spread in Prostate Cancer Patients Influencing Radiotherapy Response.
Daria Klusa,Fabian Lohaus,Giulia Furesi,Martina Rauner,Martina Benešová,Mechthild Krause,Ina Kurth,Claudia Peitzsch,Claudia Peitzsch +8 more
TLDR
In this article, a review of current clinical concepts for metastatic prostate cancer patients is presented, which discusses the implementation of recent preclinical findings improving our understanding of metastatic dissemination and radiotherapy resistance into standard of care.Abstract:
Radiotherapy and surgery are curative treatment options for localized prostate cancer (PCa) with a 5-year survival rate of nearly 100%. Once PCa cells spread into distant organs, such as bone, the overall survival rate of patients drops dramatically. The metastatic cascade and organotropism of PCa cells are regulated by different cellular subtypes, organ microenvironment, and their interactions. This cross-talk leads to pre-metastatic niche formation that releases chemo-attractive factors enforcing the formation of distant metastasis. Biological characteristics of PCa metastasis impacting on metastatic sites, burden, and latency is of clinical relevance. Therefore, the implementation of modern hybrid imaging technologies into clinical routine increased the sensitivity to detect metastases at earlier stages. This enlarged the number of PCa patients diagnosed with a limited number of metastases, summarized as oligometastatic disease. These patients can be treated with androgen deprivation in combination with local-ablative radiotherapy or radiopharmaceuticals directed to metastatic sites. Unfortunately, the number of patients with disease recurrence is high due to the enormous heterogeneity within the oligometastatic patient population and the lack of available biomarkers with predictive potential for metastasis-directed radiotherapy. Another, so far unmet clinical need is the diagnosis of minimal residual disease before onset of clinical manifestation and/or early relapse after initial therapy. Here, monitoring of circulating and disseminating tumor cells in PCa patients during the course of radiotherapy may give us novel insight into how metastatic spread is influenced by radiotherapy and vice versa. In summary, this review critically compares current clinical concepts for metastatic PCa patients and discuss the implementation of recent preclinical findings improving our understanding of metastatic dissemination and radiotherapy resistance into standard of care.read more
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PSMA-Targeting Radiopharmaceuticals for Prostate Cancer Therapy: Recent Developments and Future Perspectives.
Mohamed El Fakiri,Mohamed El Fakiri,Mohamed El Fakiri,Nicolas M. Geis,Nicolas M. Geis,Nicolas M. Geis,Nawal Ayada,Nawal Ayada,Matthias Eder,Matthias Eder,Ann-Christin Eder,Ann-Christin Eder +11 more
TL;DR: A general overview of the main milestones in the development of ligands for prostate specific membrane antigen (PSMA)-targeted radionuclide therapy, ranging from the firstly developed monoclonal antibodies to the current state-of-the-art low molecular weight entities conjugated with various radions, as well as potential future efforts related to PSMA-targeted prostate cancer therapy, can be found in this paper.
Journal ArticleDOI
Dosimetric analysis of the short-ranged particle emitter 161 Tb for radionuclide therapy of metastatic prostate cancer
Peter Bernhardt,Peter Bernhardt,Johanna Svensson,Jens Hemmingsson,Nicholas P. van der Meulen,Jan Rijn Zeevaart,Mark Konijnenberg,Cristina Müller,Jon Kindblom +8 more
TL;DR: In this article, the authors analyzed the required absorbed doses to detectable metastases when using radionuclides with prostate specific membrane antigen (PSMA)-targeting radioligands to achieve a high probability for metastatic control.
Journal ArticleDOI
GCN2 eIF2 kinase promotes prostate cancer by maintaining amino acid homeostasis
TL;DR: In this paper , the eIF2 kinase GCN2 is shown to be required for sustained growth in androgen-sensitive and castration-resistant models of prostate cancer both in vitro and in vivo, and is active in PCa patient samples.
Journal ArticleDOI
TPX2 Enhanced the Activation of the HGF/ETS-1 Pathway and Increased the Invasion of Endocrine-Independent Prostate Carcinoma Cells
Qinghong Zhou,Mingsheng Liu,Tao Shao,Pingbo Xie,Shaojie Zhu,Wei Wang,Qiong Miao,Jiaxi Peng,Peng Zhang +8 more
TL;DR: In this article, a microtubulin interacted protein (TPX2) was identified as a coactivator of ETS-1, a transcription factor that plays a central role in mediating the metastasis of human malignancies.
Journal ArticleDOI
Prostate Cancer Stem Cells: Clinical Aspects and Targeted Therapies
TL;DR: The impact of PC stem cells (PCSCs) in the clinical practice is discussed and new therapeutic approaches to combat PCSCs are presented with the aim to achieve an improved outcome for patients with PC.
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