tissue predictors of abiraterone benefit

Conditions: Metastatic Castration-resistant Prostate Cancer

Summary: this is an observational, prospective (study following participants forward in time), multi-center (study conducted in more than 1 center) study to identify the predictive factors that will effectively predict the response to abiraterone treatment in metastatic castration-resistant prostate cancer (mcrpc). the entire duration of study will be approximately 3 year. participants will primarily be evaluated for achieving biochemical or radiological progression after receiving abiraterone treatment based on eau 2017 practice guideline criteria. for this, we put our attentions on the hoxb3 (an alternative factor of wnt signaling pathway), fkbp5 (fk506 binding protein 5, androgen-regulated gene), nts (neurotensin, neuroendocrine differentiation can be induced by nts) and yap1 (yes-associated protein 1, a biomarker for cancer stem cell), which are selected from the data of gene-array for various subtypes of crpc (unpublished data). response to abiraterone treatment will also be predicted using other androgen-regulated genes like akr1c3 and pcna.

it is now accepted that castration-resistant prostate cancer (crpc) is not really androgen-independent and continues to rely on androgen signaling. abiraterone is an inhibitor of cytochrome p450 17a1 (cyp17a1) that impairs androgen-receptor signaling by depleting adrenal and intratumoral androgens. after studies showed improved survival with abiraterone, it was approved by the food and drug administration for the treatment of metastatic castration-resistant prostate cancer (mcrpc). mcrpc is a syndrome other than a disease. the mechanisms of mcrpc contain aberrant activation of androgen signaling, abnormal transition between epithelial and mesenchymal and induction of neuroendocrine differentiation (ned). in addition, cellular heterogeneity represents an omnipresent feature in human tumors, which contain cells with diverse morphology, cytogenetic markers, growth kinetics, immunological characteristics, metastatic ability, and sensitivity to therapeutics. this is an observational, prospective (study following participants forward in time), multi-center (study conducted in more than 1 center) study to identify the predictive factors that will effectively predict the response to abiraterone treatment in metastatic castration-resistant prostate cancer (mcrpc). the entire duration of study will be approximately 3 year. participants will primarily be evaluated for achieving biochemical or radiological progression after receiving abiraterone treatment based on eau 2017 practice guideline criteria. for this, we put our attentions on the fkbp5 (fk506 binding protein 5, androgen-regulated gene), nts (neurotensin, neuroendocrine differentiation can be induced by nts) and yap1 (yes-associated protein 1, a biomarker for cancer stem cell), which are selected from the data of gene-array for various subtypes of crpc. response to abiraterone treatment will also be predicted using other androgen-regulated genes like akr1c3 and pcna.

Eligibility criteria:
inclusion criteria: 1. participants who have given consent form; 2. patients with a confirmed diagnosis of mcrpc according to eau 2017 guideline; 3. serum testosterone must reach castration level: \<50 ng per deciliter; 4. participants with life expectancy of at least 6 months based on the investigator's clinical judgment. exclusion criteria: 1. participants who are allergic to contrast medium; 2. patients were excluded if they planned to receive additional concurrent anticancer therapies; 3. patients doesn't sign an informed consent form.

Keywords: prostatic neoplasms abiraterone acetate fk506 binding protein 5 neurotensin yes-associated protein 1 akr1c3 protein proliferating cell nuclear antigen