ArticleAmerican journal of cancer research2015
Melanoma patient derived xenografts acquire distinct Vemurafenib resistance mechanisms.
Article in American journal of cancer research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
20 citing papers in PubMed, 31 citations in OpenAlex.
- Review
- Dynamic Time-Resolved Remodeling of the Immune Microenvironment After Resistance to BRAF/MEK Inhibitors in Melanoma: Mechanisms, Biomarkers, and Emerging Therapeutic Strategies.International journal of molecular sciences · 2026Review
- Article
- Sustained release hydrogel for durable locoregional chemoimmunotherapy for BRAF-mutated melanoma.Journal of controlled release : official journal of the Controlled Release Society · 2023Article
- Article
- Molecular mechanisms of resistance to kinase inhibitors and redifferentiation in thyroid cancers.Endocrine-related cancer · 2022Review
- Potential Biomarkers of Skin Melanoma Resistance to Targeted Therapy-Present State and Perspectives.Cancers · 2022Review
- Review
- Glucocorticoid receptor antagonism overcomes resistance to BRAF inhibition in BRAFAmerican journal of cancer research · 2019Article
- Patient-derived xenograft mouse models: A high fidelity tool for individualized medicine.Oncology letters · 2019Review
- Overexpression of Tpl2 is linked to imatinib resistance and activation of MEK-ERK and NF-κB pathways in a model of chronic myeloid leukemia.Molecular oncology · 2018Article
- Strengths and Weaknesses of Pre-Clinical Models for Human Melanoma Treatment: Dawn of Dogs' Revolution for Immunotherapy.International journal of molecular sciences · 2018Review
- Wild-type KRAS is a novel therapeutic target for melanoma contributing to primary and acquired resistance to BRAF inhibition.Oncogene · 2018Article
- BRAFProceedings of the National Academy of Sciences of the United States of America · 2017Article
- Inhibition of oncogenic BRAF activity by indole-3-carbinol disrupts microphthalmia-associated transcription factor expression and arrests melanoma cell proliferation.Molecular carcinogenesis · 2017Article
- Article
- Melanoma central nervous system metastases: current approaches, challenges, and opportunities.Pigment cell & melanoma research · 2016Review
- miR-579-3p controls melanoma progression and resistance to target therapy.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Therapeutic implications of melanoma heterogeneity.Experimental dermatology · 2016Article
- BRAF(V600E) Kinase Domain Duplication Identified in Therapy-Refractory Melanoma Patient-Derived Xenografts.Cell reports · 2016Article
Corrections and comments
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Authors and funding
14 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Variable clinical responses, tumor heterogeneity, and drug resistance reduce long-term survival outcomes for metastatic melanoma patients. To guide and accelerate drug development, we characterized tumor responses for five melanoma patient derived xenograft models treated with Vemurafenib. Three BRAF(V600E) models showed acquired drug resistance, one BRAF(V600E) model had a complete and durable response, and a BRAF(V600V) model was expectedly unresponsive. In progressing tumors, a variety of resistance mechanisms to BRAF inhibition were uncovered, including mutant BRAF alternative splicing, NRAS mutation, COT (MAP3K8) overexpression, and increased mutant BRAF gene amplification and copy number. The resistance mechanisms among the patient derived xenograft models were similar to the resistance pathways identified in clinical specimens from patients progressing on BRAF inhibitor therapy. In addition, there was both inter- and intra-patient heterogeneity in resistance mechanisms, accompanied by heterogeneous pERK expression immunostaining profiles. MEK monotherapy of Vemurafenib-resistant tumors caused toxicity and acquired drug resistance. However, tumors were eradicated when Vemurafenib was combined the MEK inhibitor. The diversity of drug responses among the xenograft models; the distinct mechanisms of resistance; and the ability to overcome resistance by the addition of a MEK inhibitor provide a scheduling rationale for clinical trials of next-generation drug combinations.
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26101714PMC4473327W2436007325What OpenQuestion holds
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.