Drug-Resistant Mutations in ERK

The use of targeted therapeutics directed against BRAFV600-mutant metastatic melanoma improves progression-free survival in many patients; however, acquired drug resistance remains a major medical challenge. By far, the most common clinical resistance mechanism involves reactivation of the MAPK (RAF/MEK/ERK) pathway by a variety of mechanisms. Thus, targeting ERK itself has emerged as an attractive therapeutic concept, and several ERK inhibitors have entered clinical trials. We sought to preemptively determine mutations in ERK1/2 that confer resistance to either ERK inhibitors or combined RAF/MEK inhibition in BRAFV600-mutant melanoma. Using a random mutagenesis screen, we identified multiple point mutations in ERK1 (MAPK3) and ERK2 (MAPK1) that could confer resistance to ERK or RAF/MEK inhibitors. ERK inhibitor–resistant alleles were sensitive to RAF/MEK inhibitors and vice versa, suggesting that the future development of alternating RAF/MEK and ERK inhibitor regimens might help circumvent resistance to these agents. Cancer Res; 74(23); 7079–89. ©2014 AACR.
Source: Cancer Research - Category: Cancer & Oncology Authors: Tags: Therapeutics, Targets, and Chemical Biology Source Type: research

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We report the estimation of the percentage of stroma (POS) using digital pathology in a large population-ascertained cohort of primary melanomas. Consent was obtained from participants in the Leeds Melanoma Cohort Study to access and sample tumor FFPE blocks. H&E-stained slides were digitally scanned and blocks were sampled for gene expression studies using a tissue microarray needle; this yielded a core of tissue from which RNA was extracted and assayed using Illumina WGDASL.
Source: Journal of the American Academy of Dermatology - Category: Dermatology Source Type: research
Importance: Melanoma is a highly aggressive cancer with extremely poor late stage survival. Those with a previous melanoma diagnosis have a 9-fold increased risk for developing a second primary melanoma compared with the general population. Yet, guidelines for dermatologic follow-up full body skin examinations (FBSEs) after diagnosis of stage I melanoma are ill-defined and vary widely.
Source: Journal of the American Academy of Dermatology - Category: Dermatology Source Type: research
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Source: Journal of the American Academy of Dermatology - Category: Dermatology Source Type: research
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Source: Journal of the American Academy of Dermatology - Category: Dermatology Source Type: research
This study aimed to compare the quality of life (QoL) of patients with BCC against that of patients with relapse-free MM.
Source: Journal of the American Academy of Dermatology - Category: Dermatology Source Type: research
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Source: Journal of the American Academy of Dermatology - Category: Dermatology Source Type: research
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Source: Journal of the American Academy of Dermatology - Category: Dermatology Source Type: research
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Source: Journal of the American Academy of Dermatology - Category: Dermatology Source Type: research
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Source: Journal of the American Academy of Dermatology - Category: Dermatology Source Type: research
The objective of this study was to determine if nonprimary site surgery is significantly associated with improved survival outcomes.
Source: Journal of the American Academy of Dermatology - Category: Dermatology Source Type: research
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