scholarly journals Targeted Radionuclide Therapy of Prostate Cancer—From Basic Research to Clinical Perspectives

Molecules ◽  
2020 ◽  
Vol 25 (7) ◽  
pp. 1743 ◽  
Author(s):  
Malwina Czerwińska ◽  
Aleksander Bilewicz ◽  
Marcin Kruszewski ◽  
Aneta Wegierek-Ciuk ◽  
Anna Lankoff
Keyword(s):  
Prostate Cancer ◽  
Basic Research ◽  
Morbidity Rate ◽  
Castration Resistant Prostate Cancer ◽  
Mortality And Morbidity ◽  
Castration Resistant ◽  
Prostate Cancer Therapy ◽  
Specific Antigens ◽  
Almost All ◽  
New Generation

Prostate cancer is the most commonly diagnosed malignancy in men and the second leading cause of cancer-related deaths in Western civilization. Although localized prostate cancer can be treated effectively in different ways, almost all patients progress to the incurable metastatic castration-resistant prostate cancer. Due to the significant mortality and morbidity rate associated with the progression of this disease, there is an urgent need for new and targeted treatments. In this review, we summarize the recent advances in research on identification of prostate tissue-specific antigens for targeted therapy, generation of highly specific and selective molecules targeting these antigens, availability of therapeutic radionuclides for widespread medical applications, and recent achievements in the development of new-generation small-molecule inhibitors and antibody-based strategies for targeted prostate cancer therapy with alpha-, beta-, and Auger electron-emitting radionuclides.

Optic atrophy after cabazitaxel treatment in a patient with castration-resistant prostate cancer: a case report

2018 ◽  
Vol 64 (2) ◽  
pp. 71-73 ◽  
Author(s):  
Sevda Diker ◽  
Ömer Diker
Keyword(s):  
Prostate Cancer ◽  
Drug Resistance ◽  
Case Report ◽  
Adverse Effects ◽  
Optic Neuropathy ◽  
Optic Atrophy ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Anti Cancer ◽  
New Generation

Taxanes are a group of cytotoxic anti-cancer agents used in the treatment of solid tumours. The neurotoxic adverse effects of docetaxel and paclitaxel, including optic neuropathy, are well known. Cabazitaxel is a new generation taxane showing lesser drug resistance when compared with previous ones. Optic atrophy due to the use of cabazitaxel has not been previously reported. Herein, we report a patient with prostate cancer who developed optic atrophy after cabazitaxel treatment.

scholarly journals Update on the Management of Non-Metastatic Castration-Resistant Prostate Cancer

2021 ◽  
Vol 9 (3) ◽  
Author(s):  
Fernández-Hernandez L ◽  
Vives-Dilmes R ◽  
Redondo-Gonzalez E ◽  
Vives-Dilmes R ◽  
Vidal-Cassinello N ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Placebo Group ◽  
Androgen Receptor ◽  
Phase Iii ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Pubmed Database ◽  
Phase Iii Trials ◽  
Recent Phase ◽  
New Generation

Background: Non-metastatic Castration Resistant Prostate Cancer (nmCRPC) is a heterogenous disease state in which the epidemiology is not completely known. Development of more sensitive modalities for detection of metastasis as well as the emerging data on new generation Androgen Receptor (AR) pathway inhibitors, has changed the paradigm in the management of such patients. Methods: This is a clinical descriptive review. Using the key words “Non-metastatic castration resistant prostate cancer” and “Androgen receptor targeted agents” in PubMed database, we reviewed and summarized the current literature about the definition, diagnosis and treatment of nmCRPC. We highlight the results of recent Phase III trials that showed significant impact on the outcomes of treatment of nmCRPC. Primary outcome was Metastasis-free Survival (MFS) and secondary outcomes included were Overall Survival (OS) among others as well as rates of Adverse Events (AEs). Development and Discussion: The SPARTAN trial showed a median MFS for patients treated with apalutamide plus Androgen Deprivation Therapy (ADT) of 40.5 months compared to 16.2 months for patients who received ADT plus placebo [hazard ratio (HR) 0.30; 95% confidence interval (CI) 0.24-0.36; p < 0.0001). Apalutamide also showed a statistically significant benefit in OS compared to placebo, with a median of 73.9 versus 59.9 months [HR: 0.78 (95% CI: 0.64-0.96), p: 0.016]. In the PROSPER trial, the median MFS for the enzalutamide group was 36.6 months compared to 14.7 months for the placebo group [HR: 0.29 (95% CI: 0.24-0.35), p < 0.0001]. OS was significantly higher in the enzalutamide group (67 versus 56.3 months in the placebo group), reaching the statiscal significance [HR: 0.73 (95% CI: 0.61-0.89), p: 0.001]. The ARAMIS trial showed a median MFS for patients treated with darolutamide plus ADT of 40.4 months compared to 18 months for the placebo group [HR: 0.41; (95% CI: 0.34-0.5); p<0.001]. The benefit of darolutamide in OS was also clear, with a HR of 0.69 (95% CI: 0.53-0.88), p: 0.003]. Conclusions: Apalutamide, enzalutamide and darolutamide have demostrated an increase in MFS and OS with a good safety profile in patients with high risk nmCRPC. There are no recommendations in favor of any drug so far, comparative studies are needed.

scholarly journals Glucocorticoid signaling delays castration-induced regression in murine models of prostate cancer

2021 ◽  
Author(s):  
Aerken Maolake ◽  
Renyuan Zhang ◽  
Kai Sha ◽  
Shalini Singh ◽  
Chunliu Pan ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Human Prostate ◽  
Murine Models ◽  
Castration Resistant Prostate Cancer ◽  
High Frequency Ultrasound ◽  
Over Expression ◽  
Castration Resistant ◽  
Glucocorticoid Signaling ◽  
Prostate Cancer Therapy ◽  
Prostate Cancers

Androgen deprivation therapy (ADT) is the mainstay therapy for recurrent and advanced prostate cancer. While human prostate cancers initially regress following ADT, many tumors fail this therapy and recur. To understand the response of prostate cancers to ADT, we have employed high frequency ultrasound imaging to track the kinetics of tumor volume in murine models of prostate cancer. Previously, we showed that normal (non-tumor) prostate regression begins within two days of castration. Following castration, murine prostate cancers also regress but only after a delay of 3-14 days, dependent on initial tumor size. Delayed regression is observed in two distinct mouse models (MYC over-expression, PTEN-deficient) implying that the genetic lesion which initiates carcinogenesis does not play a role. Intra-tumoral androgen levels are undetectable 16 hours post-castration, arguing that residual androgen signaling is not the cause of delayed regression. Castration induces tumor cell proliferation during this period. There is an increase in the active glucocorticoids, as well as glucocorticoid receptor (GR) mRNA and protein and a set of GR-regulated genes. A selective GR inhibitor eliminates the delayed regression phenotype in both models. Thus, GR signaling is activated following castration and transiently enhances tumor proliferation. This response to ADT resembles the GR-dependent mechanism of escape for prostate cancers that are resistant to anti-androgen therapies and may provide mechanistic insight into the development of castration resistant prostate cancer. If ADT-induced GR signaling is similar in human prostate cancers, simultaneous blockade of GR and androgen receptor signaling could improve prostate cancer therapy.

scholarly journals MP34-04 A NEW GENERATION OF N-TERMINAL DOMAIN ANDROGEN RECEPTOR INHIBITORS IN CASTRATION-RESISTANT PROSTATE CANCER MODELS

2019 ◽  
Vol 201 (Supplement 4) ◽  
Author(s):  
Ronan Le Moigne* ◽  
Han-Jie Zhou ◽  
Nasrin R. Mawji ◽  
C. Adriana Banuelos ◽  
Jun Wang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Castration Resistant Prostate Cancer ◽  
Terminal Domain ◽  
Castration Resistant ◽  
Cancer Models ◽  
New Generation
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