ArticleThe British journal of dermatology2019
Harnessing autophagy to overcome mitogen-activated protein kinase kinase inhibitor-induced resistance in metastatic melanoma.
Article in The British journal of dermatology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 30 citations in OpenAlex.
- BRAF inhibitor resistance in melanoma: from resistance mechanisms to therapeutic innovations.Molecular biomedicine · 2026Review
- Cell Death Modalities in Therapy of Melanoma.International journal of molecular sciences · 2025Review
- Article
- Histone deacetylases in the regulation of cell death and survival mechanisms in resistant BRAF-mutant cancers.Cancer drug resistance (Alhambra, Calif.) · 2025Review
- Exploring the therapeutic potential of cannabinoids in cancer by modulating signaling pathways and addressing clinical challenges.Discover oncology · 2024Review
- Application of Nanomaterials and Related Drug Delivery Systems in Autophagy.Molecules (Basel, Switzerland) · 2024Review
- Autophagy in BRAF-mutant cutaneous melanoma: recent advances and therapeutic perspective.Cell death discovery · 2023Review
- Reactive Oxygen Species Regulation of Chemoresistance and Metastatic Capacity of Melanoma: Role of the Cancer Stem Cell Marker CD271.Biomedicines · 2023Article
- Phytochemical Constituents and Derivatives ofInternational journal of molecular sciences · 2023Review
- Targeting phosphoinositide signaling in cancer: relevant techniques to study lipids and novel avenues for therapeutic intervention.Frontiers in cell and developmental biology · 2023Article
- Article
- Review
- Endocannabinoid System and Tumour Microenvironment: New Intertwined Connections for Anticancer Approaches.Cells · 2021Review
- Clinical Translation of Combined MAPK and Autophagy Inhibition inInternational journal of molecular sciences · 2021Review
- The Role of Phosphatidylinositol 3-Kinase Catalytic Subunit Type 3 in the Pathogenesis of Human Cancer.International journal of molecular sciences · 2021Review
- Application of Animal Models in Cancer Research: Recent Progress and Future Prospects.Cancer management and research · 2021Review
- New insights on the role of autophagy in the pathogenesis and treatment of melanoma.Molecular biology reports · 2020Review
- Review
- Trametinib potentiates TRAIL-induced apoptosis via FBW7-dependent Mcl-1 degradation in colorectal cancer cells.Journal of cellular and molecular medicine · 2020Article
- Resveratrol suppresses melanoma growth by promoting autophagy through inhibiting the PI3K/AKT/mTOR signaling pathway.Experimental and therapeutic medicine · 2020Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
backgroundPatients with malignant melanoma often relapse after treatment with BRAF and/or mitogen-activated protein kinase kinase (MEK) inhibitors (MEKi) owing to development of drug resistance.
objectivesTo establish the temporal pattern of CD271 regulation during development of resistance by melanoma to trametinib, and determine the association between development of resistance to trametinib and induction of prosurvival autophagy.
methodsImmunohistochemistry for CD271 and p62 was performed on human naevi and primary malignant melanoma tumours. Western blotting was used to analyse expression of CD271, p62 and LC3 in melanoma subpopulations. Flow cytometry and immunofluorescence microscopy was used to evaluate trametinib-induced cell death and CD271 expression. MTS viability assays and zebrafish xenografts were used to evaluate the effect of CD271 and autophagy modulation on trametinib-resistant melanoma cell survival and invasion, respectively.
resultsCD271 and autophagic signalling are increased in stage III primary melanomas vs. benign naevi. In vitro studies demonstrate MEKi of BRAF-mutant melanoma induced cytotoxic autophagy, followed by the emergence of CD271-expressing subpopulations. Trametinib-induced CD271 reduced autophagic flux, leading to activation of prosurvival autophagy and development of MEKi resistance. Treatment of CD271-expressing melanoma subpopulations with RNA interference and small-molecule inhibitors to CD271 reduced the development of MEKi resistance, while clinically applicable autophagy modulatory agents - including Δ9-tetrahydrocannabinol and Vps34 - reduced survival of MEKi-resistant melanoma cells. Combined MEK/autophagy inhibition also reduced the invasive and metastatic potential of MEKi-resistant cells in an in vivo zebrafish xenograft.
conclusionsThese results highlight a novel mechanism of MEKi-induced drug resistance and suggest that targeting autophagy may be a translatable approach to resensitize drug-resistant melanoma cells to the cytotoxic effects of MEKi.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.