ArticleNature medicine2018
Cooperative targeting of melanoma heterogeneity with an AXL antibody-drug conjugate and BRAF/MEK inhibitors.
Article in Nature medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 144 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
144 citing papers in PubMed, 215 citations in OpenAlex.
- Phase I/II Study of AXL-Specific Antibody-Drug Conjugate Enapotamab Vedotin in Patients with Advanced Solid Tumors.Cancer research communications · 2025Trial
- MITF-Driven melanoma plasticity as a core mechanism of therapy resistance: integrating microenvironmental signaling, mechanotransduction, and metabolic reprogramming.Cell cycle (Georgetown, Tex.) · 2026Review
- Advancing antibody drug conjugates in gastrointestinal cancers.British journal of cancer · 2026Review
- AXL at the nexus of therapeutic resistance, tumor vascularization, and immune evasion in cancer.iScience · 2026Review
- Emerging organoids and organoids-on-chip platforms for translational development of antibody‒drug conjugates and next-generation bioconjugates.Acta pharmaceutica Sinica. B · 2026Review
- Single-Cell RNA-Sequencing Reveals Tumor Microenvironment Composition and Prior Therapy Modulate Response to Axl Inhibition.Cellular and molecular bioengineering · 2026Article
- Targeted therapy in BRAF‑mutant melanoma: Advances and challenges (Review).International journal of oncology · 2026Review
- Transcriptional Reprogramming by AP-1-Bound Cis-Regulatory Elements Is Associated with Melanoma Development.International journal of molecular sciences · 2026Article
- Article
- AXL is a novel ERK5/KLF4 target in MEK inhibitor-treated melanoma.Neoplasia (New York, N.Y.) · 2026Article
- FGFR1 but not S6K1/2 drives intrinsic BRAF inhibitor resistance in melanoma.Cell death discovery · 2026Article
- Reprogramming the tumor microenvironment with antibody against membrane-proximal AXL to overcome immune checkpoint blockade resistance.Signal transduction and targeted therapy · 2026Article
- Precision Oncology 2.0: Guiding Magic Bullets With Expression-Based Liquid Biopsy.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2026Article
- Drug resistance to antibody-drug conjugates: mechanisms, challenges, and perspectives.Cancer biology & medicine · 2026Review
- AXL-SHC1 signaling axis mediates adaptive resistance to HER2-targeted tyrosine kinase inhibitors in HER2-aberrant lung and gastric cancers.NPJ precision oncology · 2026Article
- Article
- RTK AXL and its Isoforms: Regulation and Implications in Cancer.Current medicinal chemistry · 2026Review
- Single-Cell-Derived Tumor Organoid (STO) arrays on a microfluidic chip for personalized drug screening to address heterogeneity-induced drug resistance in colorectal cancer.Microsystems & nanoengineering · 2025Article
- Fragment-based discovery enables direct targeting of the melanoma oncogene MITF.Nature communications · 2025Article
- Elevated Transglutaminase-2 in SOX10-Deficient Melanoma Promotes Tumor Onset and Decreases Intratumoral CD4+ T Cells.Cancer research · 2025Article
84 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
20 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Intratumor heterogeneity is a key factor contributing to therapeutic failure and, hence, cancer lethality. Heterogeneous tumors show partial therapy responses, allowing for the emergence of drug-resistant clones that often express high levels of the receptor tyrosine kinase AXL. In melanoma, AXL-high cells are resistant to MAPK pathway inhibitors, whereas AXL-low cells are sensitive to these inhibitors, rationalizing a differential therapeutic approach. We developed an antibody-drug conjugate, AXL-107-MMAE, comprising a human AXL antibody linked to the microtubule-disrupting agent monomethyl auristatin E. We found that AXL-107-MMAE, as a single agent, displayed potent in vivo anti-tumor activity in patient-derived xenografts, including melanoma, lung, pancreas and cervical cancer. By eliminating distinct populations in heterogeneous melanoma cell pools, AXL-107-MMAE and MAPK pathway inhibitors cooperatively inhibited tumor growth. Furthermore, by inducing AXL transcription, BRAF/MEK inhibitors potentiated the efficacy of AXL-107-MMAE. These findings provide proof of concept for the premise that rationalized combinatorial targeting of distinct populations in heterogeneous tumors may improve therapeutic effect, and merit clinical validation of AXL-107-MMAE in both treatment-naive and drug-resistant cancers in mono- or combination therapy.
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.