Ferroptosis inducers for prostate cancer therapy

2022 ◽  
Vol 29 ◽  
Author(s):  
Nadia Zaffaroni ◽  
Giovanni Luca Beretta
Keyword(s):  
Prostate Cancer ◽  
Metabolic Pathways ◽  
Neurological Diseases ◽  
Kidney Injury ◽  
Oxygen Species ◽  
Cellular Mechanisms ◽  
Resistant Disease ◽  
Castration Resistant ◽  
Regulated Cell Death ◽  
Prostate Cancer Therapy

Abstract: Lipid peroxidation-driven iron-dependent ferroptosis is a regulated cell death mechanism implicated in numerous disease, such as neurological diseases, kidney injury, ischemia, and tumors, including prostate cancer. The cellular mechanisms of ferrosptosis are strongly associated with iron, reactive oxygen species and aminoacid metabolic pathways. Several compounds, namely ferroptosis inducers, impact on these pathways and trigger ferroptosis by i) inhibiting Xc– transporter system, ii) impairing GPX4 functions and iii) oxidizing iron and polyunsaturated phospholipids. Preclinical studies showed that in combination with conventional anticancer drugs, ferroptosis inducers are effective in prostate cancer and in combating the progression towards the castration resistant disease. This review overviews the mechanisms implicated in ferroptosis and discusses the findings achieved in prostate cancer.

scholarly journals Ferroptosis in plants: triggers, proposed mechanisms, and the role of iron in modulating cell death

2020 ◽  
Author(s):  
Ayelén Mariana Distéfano ◽  
Gabriel Alejandro López ◽  
Nicolás Setzes ◽  
Fernanda Marchetti ◽  
Maximiliano Cainzos ◽  
...  
Keyword(s):  
Cell Death ◽  
Metabolic Pathways ◽  
Oxygen Species ◽  
Cell Death Pathway ◽  
Plant Life ◽  
Regulated Cell Death ◽  
Dependent Cell ◽  
Plant Life Cycle ◽  
High Degree

Abstract Regulated cell death plays key roles during essential processes throughout the plant life cycle. It takes part in specific developmental programs and maintains homeostasis of the organism in response to unfavorable environments. Ferroptosis is a recently discovered iron-dependent cell death pathway characterized by the accumulation of lipid reactive oxygen species. In plants, ferroptosis shares all the main hallmarks described in other systems. Those specific features include biochemical and morphological signatures that seem to be conserved among species. However, plant cells have specific metabolic pathways and a high degree of metabolic compartmentalization. Together with their particular morphology, these features add more complexity to the plant ferroptosis pathway. In this review, we summarize the most recent advances in elucidating the roles of ferroptosis in plants, focusing on specific triggers, the main players, and underlying pathways.

scholarly journals Mannose Receptor–positive Macrophage Infiltration Correlates with Prostate Cancer Onset and Metastatic Castration-resistant Disease

2019 ◽  
Vol 2 (4) ◽  
pp. 429-436 ◽  
Author(s):  
Jelani C. Zarif ◽  
Javier A. Baena-Del Valle ◽  
Jessica L. Hicks ◽  
Christopher M. Heaphy ◽  
Igor Vidal ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Mannose Receptor ◽  
Macrophage Infiltration ◽  
Resistant Disease ◽  
Castration Resistant

scholarly journals Androgen receptor antagonists for prostate cancer therapy

2014 ◽  
Vol 21 (4) ◽  
pp. T105-T118 ◽  
Author(s):  
Christine Helsen ◽  
Thomas Van den Broeck ◽  
Arnout Voet ◽  
Stefan Prekovic ◽  
Hendrik Van Poppel ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Practice ◽  
Androgen Receptor ◽  
Metastatic Prostate Cancer ◽  
Castration Resistant ◽  
Androgen Action ◽  
Conflicting Evidence ◽  
Prostate Cancer Therapy ◽  
Androgen Receptor Antagonists

Androgen deprivation is the mainstay therapy for metastatic prostate cancer (PCa). Another way of suppressing androgen receptor (AR) signaling is via AR antagonists or antiandrogens. Despite being frequently prescribed in clinical practice, there is conflicting evidence concerning the role of AR antagonists in the management of PCa. In the castration-resistant settings of PCa, docetaxel has been the only treatment option for decades. With recent evidence that castration-resistant PCa is far from AR-independent, there has been an increasing interest in developing new AR antagonists. This review gives a concise overview of the clinically available antiandrogens and the experimental AR antagonists that tackle androgen action with a different approach.

scholarly journals Systemic Alterations of Wnt Inhibitors in Patients with Prostate Cancer and Bone Metastases

2018 ◽  
Vol 2018 ◽  
pp. 1-5 ◽  
Author(s):  
Stefan Aufderklamm ◽  
Jörg Hennenlotter ◽  
Phillip Leidenberger ◽  
Steffen Rausch ◽  
Andrea Hohneder ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Bone Metastases ◽  
Serum Levels ◽  
Enzyme Linked Immunosorbent Assay ◽  
Study Cohort ◽  
Resistant Disease ◽  
Castration Resistant ◽  
Osteoblast Activity ◽  
Osteolytic Metastases ◽  
Post Hoc

Purpose. Dickkopf-1 (DKK-1) and sclerostin seem to inhibit osteoblast activity by blocking the Wnt pathway, which leads to progression of metastatic prostate cancer (PC). However, it is unknown whether serum levels of these proteins are altered in PC patients with or without metastasis. The aim of this study was to assess DKK-1 and sclerostin serum levels in PC patients, including patients with bone metastases. Methods. The study cohort (N=143) consisted of 53 controls with benign prostatic hyperplasia (BPH), 43 with localized PC (PC cM0), and 47 had PC with metastasis (PC cM1). Serum levels of DKK-1 and sclerostin were measured by enzyme-linked immunosorbent assay. Results were compared using the Kruskal-Wallis tests; post hoc analysis was performed using the Tukey-Kramer test. Results. Mean DKK-1 levels in patients with BPH (2809.4 pg/ml) (p<0.001) as well as PC cM1 (2575.5 pg/ml) (p=0.001) were significantly higher than in patients with PC cN0 cM0 (1551.8 pg/ml). Among PC cM1 patients, median DKK-1 levels were significantly lower in patients with castration-resistant disease compared to those with hormone-sensitive PC (p=0.02); in contrast, sclerostin concentrations were elevated (p=0.04). DKK-1 correlated with PSA in the cM1 group (p=0.03) and sclerostin correlated with PSA in the PC group (0.01). Conclusions. DKK-1 is involved in the progression of PC. DKK-1-mediated inhibition of osteoblasts, which contributes to tumor progression and osteolytic metastases, may also play a role in the development of metastases with osteoblastic features. The use of DKK-1 antibodies should be considered for studies including metastatic PC patients.

Clinical characteristics and outcomes of patients with prostate cancer and parenchymal brain metastases (PBM).

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 187-187
Author(s):  
Richard Martin Bambury ◽  
Vaios Hatzoglou ◽  
Kristen Rebecca Curtis ◽  
Gita V Patel ◽  
Howard I. Scher ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Brain Metastases ◽  
Clinical Characteristics ◽  
Specific Antigen ◽  
Cancer Center ◽  
Leptomeningeal Disease ◽  
Gleason Grade ◽  
Primary Malignancy ◽  
Resistant Disease ◽  
Castration Resistant

187 Background: Parenchymal brain metastases' (PBM's) are rare in prostate cancer (PCa), but the introduction of novel therapies that prolong life for metastatic disease has raised the possibility that the distribution of disease may be changing as patients live longer. In an effort to establish the clinical characteristics and outcomes of PBM as a comparator for future studies, we reviewed all cases at our institution over a 13 year period. Methods: Patients (pts) diagnosed with PBM at Memorial Sloan-Kettering Cancer Center between 2000 and 2010 were retrospectively identified by billing codes for prostate cancer, brain metastases, and no additional primary cancers. Additional cases since 2010 were manually collected prospectively. Direct extension of osseous skull metastases or leptomeningeal disease were not considered PBM. Demographic, clinical, and pathologic characteristics were recorded. Results: 5,474 pts with metastatic PCa and no other primary malignancy were identified of whom 21 had PBM. An additional four PBM cases were prospectively identified, for a total of 25 pts. Twenty two pts (88%) had prostate adenocarcinoma (adeno), of which 14 had Gleason 8 or more disease, 20 had castration resistant disease, and nine had prostate-specific antigen (PSA) less than 5ng/mL. The other three (12%) had atypical histologies (osteosarcoma, small cell carcinoma, and high grade neuroendocrine carcinoma). Median time from diagnosis of PCa to diagnosis of PBM was 3.7 years (range 0 to 19.8) and from discovery of metastatic PCa to PBM was 2.3 years (range 0 to 10). At the time of PBM diagnosis all pts had 1 or more additional site of disease - bone metastases in 20 (80%), lung in 13 (52%), liver in nine (36%). Treatments included whole brain RT in 10 (45%), surgery +/- RT in 8 (36%) and stereotactic RT in 2 (9%). Median overall survival from diagnosis of PBM was 4.3 months (0.7-18.1) in adeno pts compared with 0.7 months (0.7-1.0) in atypical histology pts. Only four pts (16%) survived 12 or more months. Conclusions: In this contemporary cohort, PBM cases were often associated with PCa of atypical histology, high Gleason grade, frequent visceral disease, and low PSA production. Survival was poor after diagnosis of PBM despite treatment. These data can be used as a comparator to track whether treatment with novel PCa therapies is altering the incidence and characteristics of CNS involvement.

scholarly journals Reactive oxygen species induction by cabazitaxel through inhibiting Sestrin-3 in castration resistant prostate cancer

Oncotarget ◽  
2017 ◽  
Vol 8 (50) ◽  
pp. 87675-87683 ◽  
Author(s):  
Takeo Kosaka ◽  
Hiroshi Hongo ◽  
Yasumasa Miyazaki ◽  
Koshiro Nishimoto ◽  
Akira Miyajima ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Reactive Oxygen Species ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant
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