Category Ranking

98%

Total Visits

921

Avg Visit Duration

2 minutes

Citations

20

Article Abstract

Despite the development of second-generation antiandrogens, acquired resistance to hormone therapy remains a major challenge in treating advanced prostate cancer. We find that cancer-associated fibroblasts (CAFs) can promote antiandrogen resistance in mouse models and in prostate organoid cultures. We identify neuregulin 1 (NRG1) in CAF supernatant, which promotes resistance in tumor cells through activation of HER3. Pharmacological blockade of the NRG1/HER3 axis using clinical-grade blocking antibodies re-sensitizes tumors to hormone deprivation in vitro and in vivo. Furthermore, patients with castration-resistant prostate cancer with increased tumor NRG1 activity have an inferior response to second-generation antiandrogen therapy. This work reveals a paracrine mechanism of antiandrogen resistance in prostate cancer amenable to clinical testing using available targeted therapies.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7472556PMC
http://dx.doi.org/10.1016/j.ccell.2020.06.005DOI Listing

Publication Analysis

Top Keywords

prostate cancer
16
antiandrogen resistance
12
resistance prostate
8
resistance
5
prostate
5
tumor microenvironment-derived
4
microenvironment-derived nrg1
4
nrg1 promotes
4
antiandrogen
4
promotes antiandrogen
4

Similar Publications

Objectives: To balance the extended functional urinary voiding and morbidity outcomes amid Ileal W and Y-shaped contrasted to spherical ileocoecal (IC) orthotopic bladders subsequent prostate-sparing radical cystectomy (PRC) versus standard radical cystoprostatectomy (RC).

Material And Methods: Two hundred eight male bladder cancer patients were grouped into 98 RC followed by 43-W, 31-Y, and 23-IC in comparison to 110 PRC followed by 35-W, 37-Y, and 38-IC. The functional voiding outcomes were determined by detailed patients' interview and urodynamic studies (UDS).

View Article and Find Full Text PDF

Prostate cancer (PCa) is the second most lethal cancer in men in the US. African American (AA) men have twice the incidence and death rate of European American (EA) men. Advanced PCa shows increased expression and activity of the DNA damage/repair pathway enzyme, poly (ADP-ribose) polymerase 1 (PARP1).

View Article and Find Full Text PDF

Introduction: The effect of inflammatory bowel disease (IBD) on adverse in-hospital outcomes after radical prostatectomy (RP) for nonmetastatic prostate cancer (PCa) is not well known.

Materials And Methods: Descriptive analyses, propensity score matching and multivariable logistic regression models were used within the National Inpatient Sample (2000-2019) RP patients, after stratification according to Crohn's disease (CD) vs. ulcerative colitis (UC) vs.

View Article and Find Full Text PDF

Background And Objective: The apex-to-base transperineal (TP) prostate biopsy needle trajectory may better sample the anterior prostate than the transrectal approach. There is evidence that African American men are more likely to harbor anterior tumors, suggesting that TP biopsy would result in better detection in these men. We performed a secondary retrospective analysis of prospective randomized trial data to determine whether African American race is associated with anterior tumor location and better detection with TP biopsy.

View Article and Find Full Text PDF