ArticleCancer cell2010
Acquired resistance to BRAF inhibitors mediated by a RAF kinase switch in melanoma can be overcome by cotargeting MEK and IGF-1R/PI3K.
Article in Cancer cell, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02583516 (A Randomized Phase II Study of Vemurafenib Plus Cobimetinib Continuous Versus Intermittent, in Previously Untreated BRAFV600- Mutation Positive Patients With Unresectable Locally Advanced or Metastatic Melanoma), which is not on this map. Cited by 707 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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.
A Randomized Phase II Study of Vemurafenib Plus Cobimetinib Continuous Versus Intermittent, in Previously Untreated BRAFV600- Mutation Positive Patients With Unresectable Locally Advanced or Metastatic Melanoma
Who cites it
707 citing papers in PubMed, 2 syntheses or guidelines pooled it, 1,226 citations in OpenAlex.
- Prognostic value of receptor tyrosine kinases in malignant melanoma patients: A systematic review and meta-analysis of immunohistochemistry.Frontiers in oncology · 2022Pooled it
- Ultrasound, CT, MRI, or PET-CT for staging and re-staging of adults with cutaneous melanoma.The Cochrane database of systematic reviews · 2019Pooled it
- Longitudinal Genomic Analysis to Fine-tune Targeted Therapy: Results of the Phase II LOGIC 2 Trial in Patients with BRAFV600-Mutant Metastatic Melanoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Trial
- The pathway alteration load is a pan-cancer determinant of outcome of targeted therapies: results from the Drug Rediscovery Protocol (DRUP).ESMO open · 2025Trial
- IGF1-IGF1R signaling in tumor-associated macrophages regulates extracellular matrix organization in BRAF inhibitor-targeted melanoma.Molecular and cellular biochemistry · 2026Article
- Therapeutic Resistance in Melanoma: Molecular Mechanisms and Emerging Pharmaceutical Strategies.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Targeted therapy in BRAF‑mutant melanoma: Advances and challenges (Review).International journal of oncology · 2026Review
- Selective mRNA translation determines adaptative mutability of melanoma cells to anti-BRAF/MEK combination therapy.EMBO molecular medicine · 2026Article
- Erk inhibitors intercept Erk-mediated negative feedback while imposing cell-cycle arrest and activating p38.iScience · 2026Article
- Review
- Melanoma-patient-derived xenograft multi-omics resource melPDomiX maps gain- and loss-of-function alterations.Cell reports · 2026Article
- Divergent CRD-Dependent Mechanisms Govern RAS Isoform-Selective Recruitment of CRAF and ARAF.bioRxiv : the preprint server for biology · 2026Article
- mTOR inhibition enhances the antitumor efficacy of pan-RAF-MEK blockade by inhibiting the ATF4-MTHFD2 pathway.Cell death & disease · 2026Article
- The neural crest-associated gene ERRFI1 is involved in melanoma progression and resistance toward targeted therapy.Molecular oncology · 2026Article
- MAPK Pathway Inhibition Reshapes Kinase Chemical Probe Reactivity Reflecting Cellular Activation States.ACS bio & med chem Au · 2026Article
- PHI-501, a dual inhibitor of RAF and DDR1/2, overcomes MAPK drug resistance in Melanoma.Cancer cell international · 2026Article
- Comparative Proteomic Analysis of the Secretome of Control and BRAF/MEK Inhibitor-Resistant Melanoma Cells.Journal of proteome research · 2026Article
- Targeting Activated Pathways in Doxorubicin-Resistant TNBC Alters Signaling, Survival and EMT: A Double-Edged Sword.International journal of molecular sciences · 2026Article
- Article
- Breaking the ERK1/2 negative feedback loop: avoiding reactivation and acquisition of resistance by ERK1/2 to anti-cancer agents.Frontiers in oncology · 2026Review
647 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
21 authors at 5 institutions in 2 countries.
Funding
Abstract
BRAF is an attractive target for melanoma drug development. However, resistance to BRAF inhibitors is a significant clinical challenge. We describe a model of resistance to BRAF inhibitors developed by chronic treatment of BRAF(V)⁶⁰⁰(E) melanoma cells with the BRAF inhibitor SB-590885; these cells are cross-resistant to other BRAF-selective inhibitors. Resistance involves flexible switching among the three RAF isoforms, underscoring the ability of melanoma cells to adapt to pharmacological challenges. IGF-1R/PI3K signaling was enhanced in resistant melanomas, and combined treatment with IGF-1R/PI3K and MEK inhibitors induced death of BRAF inhibitor-resistant cells. Increased IGF-1R and pAKT levels in a post-relapse human tumor sample are consistent with a role for IGF-1R/PI3K-dependent survival in the development of resistance to BRAF inhibitors.
Indexed as
Identifiers
What 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.