ArticleCell communication and signaling : CCS2022
PI3K/AKT signaling allows for MAPK/ERK pathway independency mediating dedifferentiation-driven treatment resistance in melanoma.
Article in Cell communication and signaling : CCS, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
34 citing papers in PubMed, 1 synthesis or guideline pooled it, 39 citations in OpenAlex.
- Exploring STK3 in melanoma: a systematic review of signaling networks and therapeutic opportunities.Molecular biology reports · 2024Pooled it
- MITF-Driven melanoma plasticity as a core mechanism of therapy resistance: integrating microenvironmental signaling, mechanotransduction, and metabolic reprogramming.Cell cycle (Georgetown, Tex.) · 2026Review
- Triptolide Suppresses Tongue Squamous Cell Carcinoma Progression via PI3K-AKT Pathway Inhibition: An Integrative Network Pharmacology and Experimental Validation Study.The Kaohsiung journal of medical sciences · 2026Article
- ANXA1-Derived Peptide Increases Melanoma Cell Sensitivity to Vemurafenib by Downregulating EphA2.Journal of cellular and molecular medicine · 2026Article
- The role of ECM mechanics in cancer mechanotransduction through unraveling the molecular machinery of integrins, FAK, and YAP signaling.Cellular & molecular biology letters · 2026Review
- A novel role of erythropoietin in skin pigmentation through melanin production.Scientific reports · 2026Article
- Multi-tyrosine kinase inhibitors: exploring immunomodulatory effects on various immune cell types in cancer.Cancer cell international · 2026Review
- AI-Guided Discovery of Oncogenic Signaling Crosstalk in Tumor Progression and Drug Resistance.Oncology research · 2026Review
- Leveraging uncertainty estimates for drug response prediction in cancer cell lines.Bioinformatics advances · 2026Article
- Oncogenic B-Raf proto-oncogene, serine/threonine kinase-mediated hedgehog signalling in the pathogenesis and targeted therapy of melanoma.World journal of clinical oncology · 2025Review
- SOX10, MITF, and microRNAs: Decoding their interplay in regulating melanoma plasticity.International journal of cancer · 2025Review
- Integrated In Silico and Experimental Validation of Antrocin as a Plant-Derived Multi-Target Therapeutic for BRAF/MEK/PI3K-Driven Colorectal Cancer.International journal of molecular sciences · 2025Article
- BRAFClinical and translational medicine · 2025Article
- Tumor dormancy and relapse: understanding the molecular mechanisms of cancer recurrence.Military Medical Research · 2025Review
- Unveiling prognostic value of JAK/STAT signaling pathway related genes in colorectal cancer: a study of Mendelian randomization analysis.Infectious agents and cancer · 2025Article
- Second-generation BRAF inhibitor Encorafenib resistance is regulated by NCOA4-mediated iron trafficking in the drug-resistant malignant melanoma cells.Scientific reports · 2025Article
- The role of FN1 gene interference in neural differentiation of human bone marrow mesenchymal stem cells.American journal of stem cells · 2025Article
- Lasalocid inhibits melanoma by down-regulating FOXM1 through PI3K/AKT and JNK/P38 MAPK pathways.Journal of Cancer · 2025Article
- Editorial: Targeting cellular signalling pathways for disease therapy: the potential of cellular reprogramming and protein kinase inhibitors.Frontiers in pharmacology · 2025Article
- Real-World Efficacy and Safety of Anti-PD-1 Antibody Plus Apatinib and Temozolomide for Advanced Acral Melanoma.Cancer management and research · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundCurrent therapeutic management of advanced melanoma patients largely depends on their BRAF mutation status. However, the vast heterogeneity of the tumors hampers the success of therapies targeting the MAPK/ERK pathway alone. Dissecting this heterogeneity will contribute to identifying key players in the oncogenic progression to tailor more effective therapies.
methodsWe performed a comprehensive molecular and phenotypic characterization of a panel of patient-derived BRAF
resultsA decrease in sensitivity to MAPK/ERK pathway inhibition with vemurafenib or trametinib corresponded with an increasing quiescence and migratory properties of the cells. This was accompanied by the loss of transcriptional signatures of melanocytic differentiation, and the gain of stem cell features that conferred highly-resistant/mesenchymal-like cells with increased xenobiotic efflux capacity. Nevertheless, targeting of the implicated ABC transporters did not improve the response to vemurafenib, indicating that incomplete BRAF inhibition due to reduced drug uptake is not a main driver of resistance. Rather, indifference to MAPK/ERK pathway inhibition arose from the activation of compensatory signaling cascades. The PI3K/AKT pathway in particular showed a higher activity in mesenchymal-like cells, conferring a lower dependency on MAPK/ERK signaling and supporting stem-like properties that could be reverted by dual PI3K/mTOR inhibition with dactolisib.
conclusionsIn case of MAPK/ERK independency, therapeutic focus may be shifted to the PI3K/AKT pathway to overcome late-stage resistance in melanoma tumors that have acquired a mesenchymal phenotype. Video Abstract.
Indexed as
Identifiers
What Socratic 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 Socratic graph.