Mechanisms of resistance to BRAF and MEK inhibitors and clinical update of US Food and Drug Administration-approved targeted therapy in advanced melanoma
Open accessAbstract
Abstract: Approximately 50% of melanomas harbor an activating BRAF mutation. Combined BRAF and MEK inhibitors such as dabrafenib and trametinib, vemurafenib and cobimetinib, and encorafenib and binimetinib are US Food and Drug Administration (FDA)-approved to treat patients with BRAF V600 -mutated advanced melanoma. Both genetic and epigenetic alterations play a major role in resistance to BRAF inhibitors by reactivation of the MAPK and/or the PI3K–Akt pathways. The role of BRAF inhibitors in modulating the immunomicroenvironment and perhaps enhancing the efficacy of checkpoint inhibitors is gaining interest. This article provides a comprehensive review of mechanisms of resistance to BRAF and MEK inhibitors in melanoma and summarizes landmark trials that led to the FDA approval of BRAF and MEK inhibitors in metastatic melanoma. Keywords: malignant melanoma, targeted therapy, BRAF inhibitor, MEK inhibitor, resistance
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Acquired resistance will invariably occur after prolonged treatment with targeted drugs, including RAF and MEK inhibitors.
“It has been long recognized that acquired resistance will invariably occur after prolonged treatment with targeted drugs, including those against Ras downstream effectors, such as RAF and MEK.72, 73, 74”
From Overcoming Resistance to Drugs Targeting KRAS Mutation (2020) · cites this paper as [73]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
The citation lists haven’t been fetched yet
References 118 · Cited by 277
Research works printed but not linked: 1
- [88]Hauschild A Grob JJ Demidov LV Dabrafenib in BRAF-mutated metastatic melanoma: a multicentre, open-label, phase 3 randomised controlled trial Lancet 2012 380 9839 358 365 22735384
- Authors
- Kakadia, S., Yarlagadda, N., Awad, R., Kundranda, M., Niu, J., Naraev, B., Mina, L., Dragovich, T., Gimbel, M., & Mahmoud, F.
- Affiliations
- University of Arkansas for Medical Sciences (US)
- Banner MD Anderson Cancer Center (US)
- Corresponding author
- Mahmoud, Fade
- ORCID
- Venue
- OncoTargets and Therapy
- Publisher
- Informa UK Limited
- Published
- 2018-10
- Volume
- Volume 11
- Pages
- 7095-7107
- ISSN
- 1178-6930 (ISSN-L)
- PMC
- PMC6200076
- OpenAlex
- W2897455122
- Cited by
- 277
- References
- 118
- Citations by year
- 2026: 16 · 2025: 28 · 2024: 26 · 2023: 28 · 2022: 52 · 2021: 50 · 2020: 47 · 2019: 30
- FWCI
- 3.33
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- OncoTargets and Therapy (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Dove Medical Press (Taylor and Francis Group) (submittedVersion, cc-by-nc)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Melanoma and MAPK Pathways
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Keywords
- advanced melanoma, BRAF V600 mutation, BRAF inhibitors, MEK inhibitors, drug resistance mechanisms, dabrafenib, trametinib, vemurafenib, cobimetinib, encorafenib, binimetinib, MAPK pathway reactivation, PI3K/Akt signaling, immune checkpoint inhibitors, targeted therapy, FDA-approved therapies
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
