ArticleJournal of experimental & clinical cancer research : CR2013
Mek inhibition results in marked antitumor activity against metastatic melanoma patient-derived melanospheres and in melanosphere-generated xenografts.
Article in Journal of experimental & clinical cancer research : CR, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 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
14 citing papers in PubMed, 20 citations in OpenAlex.
- Review
- Advanced Cellular Models for Preclinical Drug Testing: From 2D Cultures to Organ-on-a-Chip Technology.Cancers · 2022Review
- Targeting Melanoma-Initiating Cells by Caffeine: In Silico and In Vitro Approaches.Molecules (Basel, Switzerland) · 2021Article
- Heme oxygenase promotes B-Raf-dependent melanosphere formation.Pigment cell & melanoma research · 2020Article
- A novel oral micellar fenretinide formulation with enhanced bioavailability and antitumour activity against multiple tumours from cancer stem cells.Journal of experimental & clinical cancer research : CR · 2019Article
- TNF-alpha and metalloproteases as key players in melanoma cells aggressiveness.Journal of experimental & clinical cancer research : CR · 2018Article
- Expression differences of genes in the PI3K/AKT, WNT/b-catenin, SHH, NOTCH and MAPK signaling pathways in CD34+ hematopoietic cells obtained from chronic phase patients with chronic myeloid leukemia and from healthy controls.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2018Article
- Lipid Storage and Autophagy in Melanoma Cancer Cells.International journal of molecular sciences · 2017Article
- PTEN status is a crucial determinant of the functional outcome of combined MEK and mTOR inhibition in cancer.Scientific reports · 2017Article
- Targeted inhibition of MEK1 by cobimetinib leads to differentiation and apoptosis in neuroblastoma cells.Journal of experimental & clinical cancer research : CR · 2015Article
- Tyr1068-phosphorylated epidermal growth factor receptor (EGFR) predicts cancer stem cell targeting by erlotinib in preclinical models of wild-type EGFR lung cancer.Cell death & disease · 2015Article
- Phenotypic diversity of patient-derived melanoma populations in stem cell medium.Laboratory investigation; a journal of technical methods and pathology · 2015Article
- Research on tumorigenicity of cinnamaldehyde in melanoma cell lines and its mechanism.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2014Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
One of the key oncogenic pathways involved in melanoma aggressiveness, development and progression is the RAS/BRAF/MEK pathway, whose alterations are found in most patients. These molecular anomalies are promising targets for more effective anti-cancer therapies. Some Mek inhibitors showed promising antitumor activity, although schedules and doses associated with low systemic toxicity need to be defined. In addition, it is now accepted that cancers can arise from and be maintained by the cancer stem cells (CSC) or tumor-initiating cells (TIC), commonly expanded in vitro as tumorspheres from several solid tumors, including melanoma (melanospheres). Here, we investigated the potential targeting of MEK pathway by exploiting highly reliable in vitro and in vivo pre-clinical models of melanomas based on melanospheres, as melanoma initiating cells (MIC) surrogates. MEK inhibition, through PD0325901, provided a successful strategy to affect survival of mutated-BRAF melanospheres and growth of wild type-BRAF melanospheres. A marked citotoxicity was observed in differentated melanoma cells regardless BRAF mutational status. PD0325901 treatment, dramatically inhibited growth of melanosphere-generated xenografts and determined impaired tumor vascularization of both mutated- and wild type-BRAF tumors, in the absence of mice toxicity. These results suggest that MEK inhibition might represent a valid treatment option for patients with both mutated- or wild type-BRAF melanomas, affecting tumor growth through multiple targets.
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.