Combination therapy with BRAF and MEK inhibitors for melanoma: latest evidence and place in therapy

Eroglu, Zeynep; Ribas, Antoni

doi:10.1177/1758834015616934

Cited by 316Melanoma and MAPK PathwaysColorectal Cancer Treatments and StudiesLung Cancer Treatments and Mutations

Combination therapy with BRAF and MEK inhibitors for melanoma: latest evidence and place in therapy

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Eroglu, Zeynep, Ribas, Antoni·2016·Therapeutic Advances in Medical Oncology

DOI 10.1177/1758834015616934PMC PMC4699264

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Abstract

Treatment with BRAF inhibitors such as vemurafenib or dabrafenib in patients with advanced BRAFV600 mutated melanoma has shown objective tumor responses in approximately half of the patients. However, the duration of responses is limited in a majority of these patients, with progression-free survival rates around 6 months due to tumor progression from development of acquired resistance. Preclinical studies have suggested that concurrent inhibition of the BRAF kinases and MEK of the mitogen-activated protein kinase (MAPK) pathway could decrease MAPK-driven acquired resistance, resulting in longer duration of responses, higher rate of tumor responses, and a decrease in the cutaneous toxicities observed from paradoxical MAPK pathway activation with BRAF inhibitor monotherapy. This review provides an overview of the currently available clinical trial data on BRAF and MEK inhibitors together and in combinations with other therapeutic agents.

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Vertical inhibition, combining inhibitors of the same pathway, has the potential to improve survival outcomes, as illustrated by BRAF and MEK inhibitor combinations for melanoma.
“Combining inhibitors of the same pathway (termed ‘vertical inhibition’) has the potential to improve survival outcomes, as perhaps best illustrated by BRAF and MEK inhibitor combinations for melanoma93”
From The current state of the art and future trends in RAS-targeted cancer therapies (2022) · cites this paper as [93]
Resistance to vertical inhibition remains inevitable.
“but resistance remains inevitable.”
From The current state of the art and future trends in RAS-targeted cancer therapies (2022) · cites this paper as [93]
Combined BRAF and MEK targeting in melanoma increases efficacy but is still not curative.
“In this Review, we describe strategies for overcoming resistance mechanisms through vertical inhibition of multiple nodes of the RAS pathway, with specific learnings from the saga of combined BRAF and MEK targeting in melanoma, which increases efficacy but is still not curative93.”
From The current state of the art and future trends in RAS-targeted cancer therapies (2022) · cites this paper as [93]

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DI-030 Analysis of treatment with vemurafenib and dabrafenib in patients with metastasic melanoma in a tertiary hospital
Delgado, C. R., González, M. S., Gómez, G. C., et al. (2017) · doi:10.1136/ejhpharm-2017-000640.277 · Cited by 1 · see citing works
The Molecular Biology and Treatment of Malignant Melanoma with BRAFV600 Mutations
Mullane, M. P. (2014) · Journal of patient-centered research and reviews · doi:10.17294/2330-0698.1007 · Cited by 1 · see citing works

Authors: Eroglu, Z., & Ribas, A.
Affiliations: Moffitt Cancer Center (US)
University of California, Los Angeles (US)
Corresponding author: Ribas, Antoni
ORCID: Eroglu, Zeynep
Ribas, Antoni
Venue: Therapeutic Advances in Medical Oncology
Publisher: SAGE Publications
Published: 2015-12-18
Volume: 8
Issue: 1
Pages: 48-56
ISSN: 1758-8340 (ISSN-L)
1758-8359
DOI: 10.1177/1758834015616934
PMC: PMC4699264
OpenAlex: W2335844855
Cited by: 316
References: 53
Citations by year: 2026: 19 · 2025: 27 · 2024: 31 · 2023: 27 · 2022: 39 · 2021: 45 · 2020: 28 · 2019: 30 · 2018: 20 · 2017: 35 · 2016: 15
FWCI: 2.26
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: journals.sagepub.com/page/policies/text-and-data-mining-license (tdm)
Locations: Therapeutic Advances in Medical Oncology (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
eScholarship (California Digital Library) (submittedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Melanoma and MAPK Pathways
Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
Keywords: BRAF inhibitors, MEK inhibitors, combination therapy, melanoma, BRAF V600 mutation, vemurafenib, dabrafenib, MAPK signaling, acquired drug resistance, progression-free survival, skin toxicity, clinical trials

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Combination therapy with BRAF and MEK inhibitors for melanoma: latest evidence and place in therapy

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