ArticleOncogene2018
AXL/AKT axis mediated-resistance to BRAF inhibitor depends on PTEN status in melanoma.
Article in Oncogene, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
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
72 citing papers in PubMed, 113 citations in OpenAlex.
- AXL at the nexus of therapeutic resistance, tumor vascularization, and immune evasion in cancer.iScience · 2026Review
- A Rapid 3D Melanoma-Skin Organoid for High-Throughput Assessment of Tumor Dynamics and Drug Response.International journal of molecular sciences · 2026Article
- Integrative multi-omics defines melanoma drug response networks and ARID1A-dependent resistance mechanisms.Molecular systems biology · 2026Article
- Comprehensive transcriptomic characterization of two melanoma cell lines with acquired dual resistance to BRAF and MEK inhibitors.Scientific reports · 2026Article
- PROTAC-based protein degradation: a window of opportunity for melanoma therapy.Journal of biomedical science · 2026Review
- Targeting one-carbon metabolic vulnerabilities of metastasis with therapeutic potential.bioRxiv : the preprint server for biology · 2026Article
- Sodium butyrate regulates proliferation of skeletal muscle satellite cells in Arbas cashmere goats: molecular mechanisms from an in vitro study.BMC veterinary research · 2026Article
- Article
- CAR NK cell therapy for solid tumors: potential and challenges.Antibody therapeutics · 2025Review
- Article
- Targeting the PREX2/RAC1/PI3Kβ Signaling Axis Confers Sensitivity to Clinically Relevant Therapeutic Approaches in Melanoma.Cancer research · 2025Article
- Targeting TMEM16A/ANO1 inhibits the progression of BRAF mutant (V600E) melanoma through the MEK/ERK and AKT signaling pathways.Genes & diseases · 2024Article
- Functional Bidirectionality of ERV-Derived Long Non-Coding RNAs in Humans.International journal of molecular sciences · 2024Review
- Novel gene therapy for drug-resistant melanoma: Synergistic combination of PTEN plasmid and BRD4 PROTAC-loaded lipid nanocarriers.Molecular therapy. Nucleic acids · 2024Article
- Development of Personalized Strategies for Precisely Battling Malignant Melanoma.International journal of molecular sciences · 2024Review
- Review
- Therapeutic targeting of the functionally elusive TAM receptor family.Nature reviews. Drug discovery · 2024Review
- Antibody dependent cellular cytotoxicity-inducing anti-EGFR antibodies as effective therapeutic option for cutaneous melanoma resistant to BRAF inhibitors.Frontiers in immunology · 2024Article
- Oncofetal reprogramming in tumor development and progression: novel insights into cancer therapy.MedComm · 2023Review
- Review
12 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
8 authors at 4 institutions in 2 countries.
Funding
Abstract
Multiple genetic mutations within melanoma not only cause lesion-specific responses to targeted therapy but also alter the molecular route of resistance to that therapy. Inactivation of PTEN occurs in up to 30% of melanomas, frequently with a concurrent activating BRAF mutation. PTEN loss regulates both acquired and intrinsic drug resistance. Here we show that AXL/AKT axis mediated-resistance to BRAF inhibitor (BRAFi) depends upon PTEN status in melanoma. Hyperactivation of both ERK and AKT pathways was associated with BRAFi resistance in melanoma with wildtype PTEN. The PTEN-impaired melanoma cells required only the ERK resistance mechanism. Moreover, we identified AXL as a key upstream effector of AKT pathway-associated resistance to BRAFi in melanoma with wildtype PTEN, but not in melanoma with impaired PTEN. Notably, we confirmed that blocking AXL by shRNA and a small molecular inhibitor could rescue the sensitivity of resistant melanoma cells with wildtype PTEN to BRAFi and inhibit their growth in vitro and in vivo. Our study has uncovered a mechanism by which PTEN status contributes to acquired resistance to BRAFi and offers a rational strategy to guide clinical testing in pre-identified subsets of patients who relapse during treatment with BRAFi. The identified protein AXL represents a promising therapeutic target for BRAF mutant melanoma patients with wildtype PTEN.
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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.