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Glucocorticoid receptor antagonism overcomes resistance to BRAF inhibition in BRAF<sup>V600E</sup>-mutated metastatic melanoma.

Author: AlcácerJavier, BenllochMaría, EstrelaJosé M, López-BlanchRafael, MarchioPatricia, ObradorElena, PellicerJosé A, PérezCarlos L, RiveraPilar, SalvadorRosario, VallesSoraya L

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Overview

RU486, a GR antagonist, increased the efficacy of vemurafenib in BRAF<sup>V600E</sup>-mutated metastatic melanoma, especially in early stages. However, resistance developed at advanced stages, linked to overexpression of Bcl-xL and Mcl-1. Blocking AKT and NF-κB pathways reduced this resistance.
Paper Details　
Original Abstract of the Article :
Clinical applications of glucocorticoids (GC) in Oncology are dependent on their pro-apoptotic action to treat lymphoproliferative cancers, and to alleviate side effects induced by chemotherapy and/or radiotherapy. However, the mechanism(s) by which GC may also promote tumor progression remains uncl...See full text at original site
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引用元：
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6943348/

データ提供：米国国立医学図書館（NLM）

A Twist in the Tale: Overcoming Resistance to BRAF Inhibition in Melanoma

Melanoma, a deadly form of skin cancer, poses a significant challenge for oncologists. This study delves into the complexities of BRAFV600E-mutated metastatic melanoma, investigating the mechanism of resistance to BRAF inhibition and exploring potential strategies for overcoming this obstacle. The researchers meticulously examined the role of glucocorticoid receptor (GR) antagonism in enhancing the efficacy of BRAF-related therapy in melanoma.

A New Angle on Treatment: Targeting the Glucocorticoid Receptor

The study found that GR knockdown decreased the antioxidant protection of melanoma cells, suggesting that targeting the GR could enhance the effectiveness of BRAF-related therapy. The researchers tested the combined effects of a GR antagonist (RU486, mifepristone) and vemurafenib (VMF), a BRAF inhibitor, on BRAFV600E-mutated metastatic melanoma cells. This research, like a camel caravan seeking a new route through a challenging landscape, explores innovative strategies for overcoming resistance to BRAF inhibition in melanoma.

A Promising Strategy: Combining GR Antagonism with BRAF Inhibition

The study demonstrated that the combination of RU486 and VMF effectively regressed melanoma metastases in early stages of development. However, resistance to this combined therapy emerged in advanced stages of melanoma growth, a phenomenon linked to the overexpression of specific proteins within the Bcl-2 family. The researchers further explored the role of AKT and NF-κB signaling pathways in mediating this resistance. This research, like a desert explorer uncovering hidden treasures, sheds light on the intricate mechanisms underlying melanoma resistance and suggests potential strategies for overcoming this challenge.

Dr. Camel's Conclusion

This study, like a desert explorer seeking a hidden oasis, offers a promising strategy for overcoming resistance to BRAF inhibition in melanoma. By targeting the glucocorticoid receptor and exploring the role of AKT and NF-κB signaling pathways, researchers are uncovering new avenues for improving the efficacy of BRAF-related therapy, ultimately offering hope for patients battling this aggressive form of cancer.
Date :
  1. Date Completed n.d.
  2. Date Revised 2020-09-30
Further Info :

Pubmed ID

31911848

DOI: Digital Object Identifier

PMC6943348

SNS
PICO Info
in preparation
Languages

English

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