Tumor Microenvironment-Derived NRG1 Promotes Antiandrogen Resistance in Prostate Cancer.

Cancer Cell
Zeda ZhangCharles L Sawyers

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.

References

Dec 23, 2004·Endocrine-related Cancer·B Kwabi-AddoM Ittmann
Dec 5, 2006·The Journal of Biological Chemistry·Takeshi NagashimaMariko Hatakeyama
Jan 20, 2007·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Johann Sebastian de BonoJohn Graham
Apr 29, 2008·Nature Medicine·Greg FinakMorag Park
May 15, 2008·Nature Reviews. Neuroscience·Lin Mei, Wen-Cheng Xiong
Oct 3, 2008·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Ayush DagvadorjMarja T Nevalainen
Jun 10, 2009·Bioinformatics·Heng LiUNKNOWN 1000 Genome Project Data Processing Subgroup
Jun 11, 2009·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Olga DakhovaMichael Ittmann
Oct 23, 2009·Nature·Anthony J TrimboliGustavo Leone
Jan 1, 2010·American Journal of Clinical Oncology·Srikala S SridharMalcolm J Moore
Mar 12, 2010·Nature·Massimo AmmiranteMichael Karin
Oct 30, 2010·Cell·Luke A Gilbert, Michael T Hemann
Mar 30, 2011·Cancer Research·Maria A KiskowskiNeil A Bhowmick
May 1, 2012·Nature Biotechnology·Scott L CarterGad Getz
Apr 4, 2013·Science Signaling·Jianjiong GaoNikolaus Schultz
Apr 18, 2013·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Patricia LoRussoJordan Berlin
Dec 18, 2013·Cell Reports·Christof FellmannJohannes Zuber
Sep 4, 2014·The New England Journal of Medicine·Emmanuel S AntonarakisJun Luo
Oct 15, 2014·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Mary-Ellen TaplinPhilip W Kantoff
Dec 18, 2014·Genome Biology·Michael I LoveSimon Anders
Dec 23, 2014·Nature Communications·Saravana M DhanasekaranArul M Chinnaiyan

❮ Previous
Next ❯

Citations

Aug 13, 2020·Nature Reviews. Urology·Rebecca Kelsey
Jan 21, 2021·Nature Reviews. Clinical Oncology·Jiajie HouBeicheng Sun
Jan 8, 2021·Frontiers in Immunology·Florian TranPhilip Seibler
Feb 9, 2021·Frontiers in Cell and Developmental Biology·Jenniffer LinaresAlexandre Calon
Apr 4, 2021·International Journal of Molecular Sciences·Colin RaeChiara Braconi
Jun 9, 2021·Biochemical Society Transactions·Nishanth Belugali NatarajYosef Yarden
Jul 25, 2021·Cancers·Ana Maia, Stefan Wiemann
Feb 21, 2021·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Heidi M Haikala, Pasi A Jänne
Aug 12, 2020·Cancer Cell·Jacob J Orme, Haojie Huang
Sep 8, 2021·Nature Reviews. Clinical Oncology·Yang ChenRaghu Kalluri
Aug 14, 2021·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Cristina GuardiaJoan Albanell

❮ Previous
Next ❯

Datasets Mentioned

BETA
GSE147976

Methods Mentioned

BETA
xenograft
flow cytometry
xenografts
RNA-seq
Assay
Protein Assay
PCR
biopsy

Software Mentioned

PANTHER
house
Lifelines
ssGSEA
HISAT2
Seaborn
MetaMorph
R Studio
StringTie
GSEA

Related Concepts

Related Feeds

Cancer Genomics (Keystone)

Cancer genomics approaches employ high-throughput technologies to identify the complete catalog of somatic alterations that characterize the genome, transcriptome and epigenome of cohorts of tumor samples. Discover the latest research using such technologies in this feed.

Related Papers

Nihon rinsho. Japanese journal of clinical medicine
Osamu Maeda, Michiyuki Usami
Annals of Translational Medicine
Camille LanzRafael Sanchez-Salas
Nihon rinsho. Japanese journal of clinical medicine
Suzuki HiroyoshiNaoto Kamiya
© 2021 Meta ULC. All rights reserved