Evolving treatment approaches for the management of metastatic castration-resistant prostate cancer &amp;ndash; role of radium-223

Mukherji, Deborah; Dika, Imane El; Temraz, Sally; Haidar, Mohammad A.; Shamseddine, Ali

doi:10.2147/tcrm.s45667

Cited by 6 publications

(2 citation statements)

References 48 publications

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“…survival p62, IL-1b could protect PCa cells from cytotoxic chemotherapy. Despite extensive clinical studies of various drugs, including chemotherapeutic agents, radiopharmaceuticals, and bisphosphonates, androgen independent PCa, particularly bone metastatic PCa, remains incurable [Beltran et al, 2011;Mukherji et al, 2014]. Therefore, based on our data, we contend that IL-1btargeted therapy should be explored as an adjuvant to both mitigate and treat androgen independent PCa.…”

Section: Il-1b Can Contribute To Androgen-independent Pca By Repressimentioning

confidence: 87%

IL‐1β Induces p62/SQSTM1 and Represses Androgen Receptor Expression in Prostate Cancer Cells

Chang

Patel

Gwede

et al. 2014

J of Cellular Biochemistry

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Chronic inflammation is associated with advanced prostate cancer (PCa), although the mechanisms governing inflammation-mediated PCa progression are not fully understood. PCa progresses to an androgen independent phenotype that is incurable. We previously showed that androgen independent, androgen receptor negative (AR−) PCa cell lines have high p62/SQSTM1 levels required for cell survival. We also showed that factors in the HS-5 bone marrow stromal cell (BMSC) conditioned medium can upregulate p62 in AR+ PCa cell lines, leading us to investigate AR expression under those growth conditions. In this paper, mRNA, protein, and subcellular analyses reveal that HS-5 BMSC conditioned medium represses AR mRNA, protein, and nuclear accumulation in the C4-2 PCa cell line. Using published gene expression data, we identify the inflammatory cytokine, IL-1β, as a candidate BMSC paracrine factor to regulate AR expression and find that IL-1β is sufficient to both repress AR and upregulate p62 in multiple PCa cell lines. Immunostaining demonstrates that, while the C4-2 population shows a primarily homogeneous response to factors in HS-5 BMSC conditioned medium, IL-1β elicits a strikingly heterogeneous response; suggesting that there are other regulatory factors in the conditioned medium. Finally, while we observe concomitant AR loss and p62 upregulation in IL-1β-treated C4-2 cells, silencing of AR or p62 suggests that IL-1β regulates their protein accumulation through independent pathways. Taken together, these in vitro results suggest that IL-1β can drive PCa progression in an inflammatory microenvironment through AR repression and p62 induction to promote the development and survival of androgen independent PCa.

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Section: Il-1b Can Contribute To Androgen-independent Pca By Repressimentioning

confidence: 87%

IL‐1β Induces p62/SQSTM1 and Represses Androgen Receptor Expression in Prostate Cancer Cells

Chang

Patel

Gwede

et al. 2014

J of Cellular Biochemistry

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“…Bone metastases dominate, but lymph node and visceral metastases are also frequent in mCRPC patients [ 4 , 5 , 6 ]. Treatment options for mCRPC have expanded rapidly in the last 20 years [ 7 , 8 , 9 , 10 , 11 ]. The US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have introduced docetaxel (chemotherapy, approved in 2004/2007), cabazitaxel (chemotherapy, approved in 2010/2011), sipuleucel-T (autologous immunotherapy, approved in 2010/2013), abiraterone acetate (hormone therapy, approved in 2011/2011), enzalutamide (hormone therapy, approved in 2010/2013), Xofigo (radium-223, targeted alpha therapy, approved in 2013/2013), olaparib (PARP inhibitor therapy, approved in 2020/-), and rucaparib (PARP inhibitor therapy, approved in 2020/-) for the treatment of mCRPC [ 7 , 8 , 9 , 10 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

Preclinical and Clinical Status of PSMA-Targeted Alpha Therapy for Metastatic Castration-Resistant Prostate Cancer

Juzeniene

Stenberg

Bruland

et al. 2021

Cancers

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Bone, lymph node, and visceral metastases are frequent in castrate-resistant prostate cancer patients. Since such patients have only a few months’ survival benefit from standard therapies, there is an urgent need for new personalized therapies. The prostate-specific membrane antigen (PSMA) is overexpressed in prostate cancer and is a molecular target for imaging diagnostics and targeted radionuclide therapy (theragnostics). PSMA-targeted α therapies (PSMA-TAT) may deliver potent and local radiation more selectively to cancer cells than PSMA-targeted β- therapies. In this review, we summarize both the recent preclinical and clinical advances made in the development of PSMA-TAT, as well as the availability of therapeutic α-emitting radionuclides, the development of small molecules and antibodies targeting PSMA. Lastly, we discuss the potentials, limitations, and future perspectives of PSMA-TAT.

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Radium-223 dichloride in clinical practice: a review

Florimonte

Dellavedova

Maffioli

2016

Eur J Nucl Med Mol Imaging

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The onset of skeletal metastases is typical of advanced-stage prostate cancer and requires a multidisciplinary approach to alleviate bone pain and try to delay disease progression. The current therapeutic armamentarium includes conventional analgesics, chemotherapeutic agents, immunotherapy, androgen-deprivation therapy, osteoclast inhibitors (bisphosphonates, denosumab), surgical interventions, external-beam radiotherapy and radionuclide metabolic therapy. Many studies in recent decades have demonstrated the efficacy of various radiopharmaceuticals, including strontium-89 and samarium-153, for palliation of pain from diffuse skeletal metastases, but no significant benefit in terms of disease progression and overall survival has been shown. The therapeutic landscape of metastatic skeletal cancer significantly changed after the introduction of radium-223, the first bone-homing radiopharmaceutical with disease-modifying properties. In this paper we extensively review the literature on the use of radium-223 dichloride in metastatic castration-resistant prostate cancer.

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Evolving treatment approaches for the management of metastatic castration-resistant prostate cancer – role of radium-223

Cited by 6 publications

References 48 publications

IL‐1β Induces p62/SQSTM1 and Represses Androgen Receptor Expression in Prostate Cancer Cells

IL‐1β Induces p62/SQSTM1 and Represses Androgen Receptor Expression in Prostate Cancer Cells

Preclinical and Clinical Status of PSMA-Targeted Alpha Therapy for Metastatic Castration-Resistant Prostate Cancer

Radium-223 dichloride in clinical practice: a review

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