Use of nuclear-localized androgen receptor splice variant 7 protein in CTCs after 1st androgen receptor signaling inhibitor (ARSi) as a predictive biomarker for overall survival on a second ARSi or taxane chemotherapy in metastatic castration-resistant prostate cancer (mCRPC)

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Home > Expanding Androgen- and Androgen Receptor Signaling–Directed Therapies for Castration-Resistant Prostate Cancer Expanding Androgen- and Androgen Receptor Signaling– Directed Therapies for Castration-Resistant Prostate Cancer

Since the discovery by Huggins and Hodges in 1941 that prostate cancer is an androgen-dependent disease,[2] the mainstay of therapy for advanced disease has been androgen deprivation therapy (ADT). Unfortunately, after a variable period of time on ADT, patients eventually progress to the lethal form of prostate cancer in the setting of castrate levels of testosterone. During the past several ye...

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Androgen receptor variant-7: an important predictive biomarker in castrate resistant prostate cancer

The recent manuscript in New England Journal of Medicine by Antonarakis et al. [1] has important clinical implications. This study evaluates mRNA expression of a particular androgen receptor splice variant-7 (AR-V7), in circulating tumor cells (CTCs) from metastatic castrate-resistant prostate cancer (mCRPC) patients receiving enzalutamide or abiraterone. The findings were striking, none of the...

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Inhibiting androgen receptor nuclear entry in castration-resistant prostate cancer

Clinical resistance to the second-generation antiandrogen enzalutamide in castration-resistant prostate cancer (CRPC), despite persistent androgen receptor (AR) activity in tumors, highlights an unmet medical need for next-generation antagonists. We have identified and characterized tetra-aryl cyclobutanes (CBs) as a new class of competitive AR antagonists that exhibit a unique mechanism of act...

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Androgen receptor splice variants determine taxane sensitivity in prostate cancer.

Prostate cancer growth depends on androgen receptor signaling. Androgen ablation therapy induces expression of constitutively active androgen receptor splice variants that drive disease progression. Taxanes are a standard of care therapy in castration-resistant prostate cancer (CRPC); however, mechanisms underlying the clinical activity of taxanes are poorly understood. Recent work suggests tha...

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Analytical Validation and Clinical Qualification of a New Immunohistochemical Assay for Androgen Receptor Splice Variant-7 Protein Expression in Metastatic Castration-resistant Prostate Cancer

BACKGROUND The androgen receptor splice variant-7 (AR-V7) has been implicated in the development of castration-resistant prostate cancer (CRPC) and resistance to abiraterone and enzalutamide. OBJECTIVE To develop a validated assay for detection of AR-V7 protein in tumour tissue and determine its expression and clinical significance as patients progress from hormone-sensitive prostate cancer (...

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ژورنال

عنوان ژورنال: Annals of Oncology

سال: 2018

ISSN: 0923-7534

DOI: 10.1093/annonc/mdy284.045