Ferroptosis inducers for prostate cancer therapy

2022 ◽  
Vol 29 ◽  
Author(s):  
Nadia Zaffaroni ◽  
Giovanni Luca Beretta

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.

Author(s):  
Ayelén Mariana Distéfano ◽  
Gabriel Alejandro López ◽  
Nicolás Setzes ◽  
Fernanda Marchetti ◽  
Maximiliano Cainzos ◽  
...  

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.


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 ◽  
...  

2014 ◽  
Vol 21 (4) ◽  
pp. T105-T118 ◽  
Author(s):  
Christine Helsen ◽  
Thomas Van den Broeck ◽  
Arnout Voet ◽  
Stefan Prekovic ◽  
Hendrik Van Poppel ◽  
...  

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.


2018 ◽  
Vol 2018 ◽  
pp. 1-5 ◽  
Author(s):  
Stefan Aufderklamm ◽  
Jörg Hennenlotter ◽  
Phillip Leidenberger ◽  
Steffen Rausch ◽  
Andrea Hohneder ◽  
...  

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.


2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 187-187
Author(s):  
Richard Martin Bambury ◽  
Vaios Hatzoglou ◽  
Kristen Rebecca Curtis ◽  
Gita V Patel ◽  
Howard I. Scher ◽  
...  

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.


Oncotarget ◽  
2017 ◽  
Vol 8 (50) ◽  
pp. 87675-87683 ◽  
Author(s):  
Takeo Kosaka ◽  
Hiroshi Hongo ◽  
Yasumasa Miyazaki ◽  
Koshiro Nishimoto ◽  
Akira Miyajima ◽  
...  

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