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Adverse Effects of Vemurafenib on Skin Integrity: Hyperkeratosis and Skin Cancer Initiation Due to Altered MEK/ERK-Signaling and MMP Activity.

Author: BoukampPetra, HarwoodCatherine, JauchAnna, Pavez LorieElizabeth, StarkHans-Jürgen, ThamMarius

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

Overview

Vemurafenib is a BRAF inhibitor used to treat melanoma. However, vemurafenib can cause cutaneous adverse events, including hyperkeratotic skin lesions and cutaneous squamous cell carcinomas (cSCC). The authors investigated the effects of vemurafenib on keratinocytes with different genetic backgrounds in vitro and in skin equivalents. They found that vemurafenib activated MEK-ERK signaling in both keratinocytes and fibroblasts, leading to a differentiation phenotype that could potentially contribute to hyperkeratosis. Importantly, they identified an important role for the RAS-RAF-MEK-ERK/MMP axis in the development of invasive growth in transformed keratinocytes. Co-treatment with vemurafenib and the MEK inhibitor cobimetinib prevented MEK-ERK hyperactivation and abolished both the differentiation and invasion phenotypes, suggesting that these adverse events are under direct control of vemurafenib-dependent MEK-ERK hyperactivation.
Paper Details　
Original Abstract of the Article :
The BRAF inhibitor vemurafenib, approved for treating patients with BRAF V600E-mutant and unresectable or metastatic melanomas, rapidly induces cutaneous adverse events, including hyperkeratotic skin lesions and cutaneous squamous cell carcinomas (cSCC). To determine, how vemurafenib would provoke t...See full text at original site
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引用元：
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8842679/

データ提供：米国国立医学図書館（NLM）

Vemurafenib's Skin Side Effects: Unraveling the Molecular Mechanisms

The field of [oncology] is constantly seeking new and effective therapies to combat [cancer]. This research focuses on the [BRAF inhibitor vemurafenib], a drug used to treat [melanoma]. The researchers investigate the [cutaneous adverse events] associated with [vemurafenib], specifically [hyperkeratotic skin lesions] and [cutaneous squamous cell carcinomas (cSCC)].

The study reveals that [vemurafenib] activates the [MEK-ERK signaling pathway] in both [keratinocytes] and [fibroblasts], leading to a complex interplay of cell differentiation and proliferation. These findings provide valuable insights into the molecular mechanisms underlying the [cutaneous adverse events] associated with [vemurafenib] and suggest potential strategies for mitigating these side effects.

Unveiling the Molecular Mechanisms: Vemurafenib's Skin Side Effects

This research sheds light on the molecular mechanisms underlying the [cutaneous adverse events] associated with [vemurafenib]. The study demonstrates that the [BRAF inhibitor] activates the [MEK-ERK signaling pathway], leading to a complex interplay of cell differentiation and proliferation, contributing to the observed skin side effects.

Navigating the Side Effects: Vemurafenib's Impact on Skin Integrity

This research raises awareness about the potential [cutaneous adverse events] associated with [vemurafenib], particularly [hyperkeratotic skin lesions] and [cSCC]. The study emphasizes the importance of understanding the underlying molecular mechanisms to potentially develop strategies for mitigating these side effects, ensuring patient safety and improving treatment outcomes.

Dr. Camel's Conclusion

This research explores the molecular mechanisms underlying the [cutaneous adverse events] associated with [vemurafenib], a [BRAF inhibitor] used to treat [melanoma]. The study provides valuable insights into the activation of the [MEK-ERK signaling pathway] and its impact on cell differentiation and proliferation. This understanding is crucial for developing strategies to mitigate these side effects and ensure patient safety during treatment.

Date :
  1. Date Completed n.d.
  2. Date Revised 2022-02-19
Further Info :

Pubmed ID

35174094

DOI: Digital Object Identifier

PMC8842679

Related Literature

Article Analysis
・Effects of vemurafenib
SNS
PICO Info
in preparation
Languages

English

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