V211D mutation in MEK1 causes resistance to MEK inhibitors in colon cancer

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class="bread-arrow"></span> <span class="breadcrumb_last" aria-current="page">V211D mutation in MEK1 causes resistance to MEK inhibitors in colon cancer</span></span></div></div> <div class="resources-filters"> <div class="_1300-container inner-content resources-filters"> <div class="resources-link-wrap" data-ix="resources-detail"> <a href="#" class="resouces-link">FILTER聽RESOURCES</a> <div class="arrow-down open"></div> <div class="arrow-up closed"></div> </div> <div class="resources-filters-grid"> <a href="/resources/" class="button resource-filter w-button"> ALL </a> <a href="/resources/featured/" class="button resource-filter w-button"> FEATURED </a> <a href="/resources/publications/" class="button resource-filter pb w-button"> PUBLICATIONS </a> <a href="/resources/presentations/" class="button resource-filter sp w-button"> SCIENTIFIC聽PRESENTATIONS </a> <a href="/resources/spotlights/" class="button resource-filter rs w-button"> RESEARCHER聽SPOTLIGHTS </a> <a href="/resources/videos/" class="button resource-filter vd w-button"> VIDEOS </a> <a href="/resources/brochures/" class="button resource-filter br w-button"> BROCHURES </a> <a href="/resources/datasets/" class="button resource-filter ds w-button"> DATASETS </a> <a href="/resources/user-guides/" class="button resource-filter ug w-button"> USER聽GUIDES </a> <a href="/resources/technical-notes/" class="button resource-filter tn w-button"> TECHNICAL聽NOTES </a> <a href="/resources/posters/" class="button resource-filter pt w-button"> POSTERS </a> <a href="/resources/ebooks/" class="button resource-filter pt w-button"> EBOOKS </a> </div> </div> </div> <div class="resources-wrap detail"> <div class="single_publication_header"> <div class="_1300-container inner-content"> <h2>Publications</h2> </div> </div> <div class="_1300-container inner-content resource"> <div class="single_publication_left"> <div class="resource-detail-title"> <div class="resource-detail-title-copy"> <h1 class="resource-detail-main-title">V211D mutation in MEK1 causes resistance to MEK inhibitors in colon cancer</h1> <br/> <div class="resource-detail-author"> Gao Y, Maria A, Na N, da Cruz Paula A, Gorelick AN, Hechtman JF, Carson J, Lefkowitz RA, Weigelt B, Taylor BS, Zhao H, Reis-Filho JS, de Stanchina E, Rosen N, Yao Z, Yaeger R. <div class="resource-detail-author_another_info"> Cancer Discovery <span class="dot"></span> Sep 2019 </div> </div> </div> </div> <div class="resource-content"> <div class="resource-detail-abstract">Abstract</div> <p>We report the emergence of the novel MEK1 V211D gatekeeper mutation in a patient with BRAF K601E colon cancer treated with the allosteric MEK inhibitor binimetinib and the anti-EGFR antibody panitumumab. The MEK1 V211D mutation concurrently occurs in the same cell with BRAF K601E and leads to RAF-independent activity but remains regulated by RAF. The V211D mutation causes resistance to binimetinib by both increasing the catalytic activity of MEK1 and reducing its affinity for the drug. Moreover, the mutant exhibits reduced sensitivity to all the allosteric MEK inhibitors tested. Thus, this mutation serves as a general resistance mutation for current MEK inhibitors; however, it is sensitive to a newly reported ATP-competitive MEK inhibitor, which therefore could be used to overcome drug resistance. SIGNIFICANCE: We report a resistance mechanism to allosteric MEK inhibitors in the clinic. A MEK1 V211D mutation developed in a patient with BRAF K601E colon cancer on MEK and EGFR inhibitors. This mutant increases the catalytic activity of MEK1 and reduces its affinity for binimetinib, but remains sensitive to ATP-competitive MEK inhibitors.This article is highlighted in the In This Issue feature, p. 1143.</p> </div> <a target="_blank" href="https://pubmed.ncbi.nlm.nih.gov/31227518/" class="button w-button">VIEW</a> </div> <div class="single_publication_right"> <div class="single_publication_right__info"> <h4>Area</h4> Solid Tumor </div> <div class="single_publication_right__info"> <h4>Institution Type</h4> Academia </div> <div class="single_publication_right__info"> <h4>Indication / Modality</h4> Colon Cancer </div> <div class="single_publication_right__info"> <h4>Goal of Study</h4> Therapeutic Resistance, Clonal Evolution, Retrospective, Longitudinal, Tumor Profiling, Disease Modeling </div> <div class="single_publication_right__info"> <h4>Key Genes</h4> BRAF, MEK1 </div> <div class="single_publication_right__info"> <h4>PAD Project</h4> No </div> <div class="single_publication_right__info"> <h4>Analytes Assessed</h4> InDels, SNV </div> <div class="single_publication_right__info"> <h4>Sample Storage</h4> Fresh Frozen </div> <div class="single_publication_right__info"> <h4>Sample Prep</h4> Whole Cells </div> <div class="single_publication_right__info"> <h4>Sample Type</h4> Patient Derived Xenograft </div> <div class="single_publication_right__info"> <h4>Tissue / Organ</h4> Colon </div> <div class="single_publication_right__info"> <h4>Species</h4> Mouse </div> <div class="single_publication_right__info"> <h4>Panel Used</h4> Tumor Hotspot Panel </div> <div class="single_publication_right__info"> <h4>Proof Point Demonstrated</h4> Co-occurrence, Zygosity </div> </div> </div> <script type="text/javascript" src="https://missionbio.com/wp-content/themes/missionbio-v2/js/jquery-3.4.1.min.js?ver=1590639462" id="jquery-js"></script> <script type="text/javascript" src="https://missionbio.com/wp-content/themes/missionbio-v2/js/swiper-bundle.min.js?ver=1.0" id="swiper-script-js"></script> <script type="text/javascript" src="https://missionbio.com/wp-content/themes/missionbio-v2/js/slick.min.js?ver=1.0" id="slick-script-js"></script> <script type="text/javascript" src="https://missionbio.com/wp-content/themes/missionbio-v2/js/mission-bio.js?ver=1666878465" id="mb-scripts-js"></script> <script type="text/javascript" src="https://missionbio.com/wp-content/themes/missionbio-v2/script.js?ver=1727345272" id="mb-main-js"></script> <script type="text/javascript" src="https://missionbio.com/wp-content/plugins/pardot/js/asyncdc.min.js?ver=6.7" id="pddc-js"></script> <div class="g-footer"> <div class="_1300-container inner-content"> <div class="g-footer-grid"> <div class="g-footer-col-logo"> <a href="/" class="g-footer-logo w-inline-block"> <img src="/wp-content/themes/missionbio-v2/images/MB-Logo-Stacked-White.svg" alt=""> </a> <div class="g-footer-social-grid"> <a target="_blank" href="https://twitter.com/missionbio?lang=en" class="g-footer-social-link tw w-inline-block"></a> <a target="_blank" href="https://www.facebook.com/missionbio/" class="g-footer-social-link fb w-inline-block"></a> <a target="_blank" href="https://www.linkedin.com/company/mission-bio" class="g-footer-social-link ln w-inline-block"></a> <a target="_blank" href="https://www.youtube.com/channel/UC3xFKde4blclowu-FbYMFeA" class="g-footer-social-link yt w-inline-block"></a> </div> <div class="g-footer-title">HEADQUARTERS</div> <div class="address">400 E Jamie Court, Suite 100<br>South San Francisco, CA 94080</div> <a href="tel:+14158540058" class="g-footer-link mb">+1 (415) 854-0058</a> <a href="mailto:info@missionbio.com" class="g-footer-link">info@missionbio.com</a> <div class="f-copyright">漏2024 Mission Bio. 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V211D mutation in MEK1 causes resistance to MEK inhibitors in colon cancer | Mission Bio