The changing landscape in the treatment of metastatic castration-resistant prostate cancer

El-Amm, Joelle; Aragon‐Ching, Jeanny B.

doi:10.1177/1758834012458137

Cited by 40 publications

(35 citation statements)

References 62 publications

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“…41 These new therapies have ameliorated the overall survival of patients from 6-10 months to up to 24 months for certain therapies. 43,44 Despite these clinical improvements, it is clear that additional therapeutic advances are needed. Recent studies have demonstrated that the progression of CRPC and the development of resistance to current treatments were associated with an increased activity of tyrosine kinase signaling.…”

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confidence: 99%

A combination of sorafenib and nilotinib reduces the growth of castrate-resistant prostate cancer

Archibald

Pritchard

Nehoff

et al. 2016

IJN

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Castrate-resistant prostate cancer (CRPC) remains incurable due to the lack of effective therapies. Several tyrosine kinases have been implicated in the development and growth of CRPC, as such targeting these kinases may offer an alternative therapeutic strategy. We established the combination of two tyrosine kinase inhibitors (TKIs), sorafenib and nilotinib, as the most cytotoxic. In addtion, to improve their bioavailability and reduce their metabolism, we encapsulated sorafenib and nilotinib into styrene- co -maleic acid micelles. The micelles’ charge, size, and release rate were characterized. We assessed the effect of the combination on the cytotoxicity, cell cycle, apoptosis, protein expression, tumor spheroid integrity, migration, and invasion. The micelles exhibited a mean diameter of 100 nm, a neutral charge, and appeared highly stable. The micellar TKIs promoted greater cytotoxicity, decreased cell proliferation, and increased apoptosis relative to the free TKIs. In addition, the combination reduced the expression and activity of several tyrosine kinases and reduced tumor spheroid integrity and metastatic potential of CRPC cell lines more efficiently than the single treatments. The combination increased the therapeutic potential and demonstrated the relevance of a targeted combination therapy for the treatment of CRPC. In addition, the efficacy of the encapsulated drugs provides the basis for an in vivo preclinical testing.

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confidence: 99%

A combination of sorafenib and nilotinib reduces the growth of castrate-resistant prostate cancer

Archibald

Pritchard

Nehoff

et al. 2016

IJN

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“…Several recommendations have been made to effectively sequence these agents. We have proposed a schema that looks at overall disease burden and presence or lack of symptoms as a guide for choice of therapy [4,11]. The National Cancer Comprehensive Network (NCCN) algorithm takes into account the presence of symptoms and stratifies whether one should receive docetaxel for symptomatic disease versus sipuleucel-T or abiraterone acetate for asymptomatic disease [12].…”

Section: History Of Drug Development Approvals and Treatment For Mcrpcmentioning

confidence: 99%

Is There an Optimal Treatment Sequencing Strategy for Metastatic Castration-Resistant Prostate Cancer?

Aragon‐Ching

2013

Future Oncol.

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“…15,16 Since 2010, five new agents have been approved by the US FDA, namely, the CYP17 lyase inhibitor abiraterone acetate, the antiandrogen enzalutamide, the T-cell activator sipuleucel-T, the microtubule stabilizer cabazitaxel, and the radiopharmaceutical radium−223. 17,18 Given the emergence of these new agents and the increased use of bone-targeted therapies (bisphosphonates and denosumab) in standard practice, the rate of reported SREs has been steadily declining. 19 This review will describe the bone-targeted therapies in mCRPC (see Table 1) and provide insight into their current and future use.…”

Section: Targeting Bone Metastases In Metastatic Castration-resistantmentioning

confidence: 99%

Targeting Bone Metastases in Metastatic Castration-Resistant Prostate Cancer

El-Amm

Aragon‐Ching²

2016

Clin Med Insights Oncol

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Skeletal involvement in metastatic castrate-resistant prostate cancer (mCRPC) is common and results in significant morbidity and mortality. The interaction of prostate cancer with the bone microenvironment contributes to progression of cancer in the bone leading to skeletal-related events (SREs). Studies aimed at targeting the bone have been carried out over the recent years. Bisphosphonates are synthetic pyrophosphate analogs first investigated for their role in SRE prevention with zoledronic acid as the main bisphosphonate that is approved by the US Food and Drug Administration for retardation of skeletal events in men with metastatic prostate cancer. Denosumab is another bone-targeted agent against uncontrolled osteolysis and serves as a RANK ligand inhibitor, superior to zoledronic acid in delaying SREs. Radiopharmaceuticals have played a role in targeting the bone microenvironment mainly in pain palliation in mCRPC utilizing strontium or samarium in the remote past, but only radium-223 is the first radiopharmaceutical that has yielded improvement in overall survival. The combination and sequencing strategies of these agents is the subject of multiple ongoing trials to guide the best use of these emerging agents.

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The changing landscape in the treatment of metastatic castration-resistant prostate cancer

Cited by 40 publications

References 62 publications

A combination of sorafenib and nilotinib reduces the growth of castrate-resistant prostate cancer

A combination of sorafenib and nilotinib reduces the growth of castrate-resistant prostate cancer

Is There an Optimal Treatment Sequencing Strategy for Metastatic Castration-Resistant Prostate Cancer?

Targeting Bone Metastases in Metastatic Castration-Resistant Prostate Cancer

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