ArticleOncogene2017
Dual MET/EGFR therapy leads to complete response and resistance prevention in a MET-amplified gastroesophageal xenopatient cohort.
Article in Oncogene, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 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
18 citing papers in PubMed, 32 citations in OpenAlex.
- A non-randomized, open-label, single-arm, Phase 2 study of emibetuzumab in Asian patients with MET diagnostic positive, advanced gastric cancer.Cancer chemotherapy and pharmacology · 2017Trial
- Fatty acid synthase as a new therapeutic target for HER2-positive gastric cancer.Cellular oncology (Dordrecht, Netherlands) · 2023Article
- BRCA2 Germline Mutations Identify Gastric Cancers Responsive to PARP Inhibitors.Cancer research · 2023Article
- Efficacy of CAR-T immunotherapy in MET overexpressing tumors not eligible for anti-MET targeted therapy.Journal of experimental & clinical cancer research : CR · 2022Article
- hOA-DN30: a highly effective humanized single-arm MET antibody inducing remission of 'MET-addicted' cancers.Journal of experimental & clinical cancer research : CR · 2022Article
- Review
- Personalized therapeutic strategies in HER2-driven gastric cancer.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2021Article
- MET Exon 14 Skipping: A Case Study for the Detection of Genetic Variants in Cancer Driver Genes by Deep Learning.International journal of molecular sciences · 2021Article
- Review
- Article
- Reactive Oxygen Species Are Involved in the Development of Gastric Cancer and Gastric Cancer-Related Depression through ABL1-Mediated Inflammation Signaling Pathway.Oxidative medicine and cellular longevity · 2019Article
- Sonic hedgehog pathway activation is associated with cetuximab resistance and EPHB3 receptor induction in colorectal cancer.Theranostics · 2019Article
- miR-205 mediates adaptive resistance to MET inhibition via ERRFI1 targeting and raised EGFR signaling.EMBO molecular medicine · 2018Article
- Neuropilin-1 upregulation elicits adaptive resistance to oncogene-targeted therapies.The Journal of clinical investigation · 2018Article
- The multiple paths towards MET receptor addiction in cancer.Oncogene · 2018Review
- Linking drug target and pathway activation for effective therapy using multi-task learning.Scientific reports · 2018Article
- Rituximab Treatment Prevents Lymphoma Onset in Gastric Cancer Patient-Derived Xenografts.Neoplasia (New York, N.Y.) · 2018Article
- Evolving Management Strategies for Metastatic Esophageal and Gastroesophageal Junction Adenocarcinoma.Oncology & hematology review · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Amplification of the MET oncogene occurs in 2-4% of gastroesophageal cancers and defines a small and aggressive subset of tumors. Although in vitro studies have given very promising results, clinical trials with MET inhibitors have been disappointing, showing few and short lasting responses. The aim of the work was to exploit a MET-amplified patient-derived xenograft model to optimize anti-MET therapeutic strategies in gastroesophageal cancer. We found that despite the high MET amplification level (26 gene copies), in the absence of qualitative or quantitative alterations of EGFR, MET inhibitors induced only tumor growth inhibition, whereas dual MET/EGFR inhibition led to complete tumor regression. Importantly, the combo treatment completely prevented the onset of resistance, which quite rapidly appeared in tumors treated with MET monotherapy. We found that this secondary resistance was due to EGFR activation and could be overcome by dual MET/EGFR inhibition. Similar results were also obtained in a MET-addicted, established gastric cancer cell line. In vitro experiments performed on tumor-derived primary cells confirmed that MET inhibitors were not able to abrogate the activation of downstream transducers and that only the combined MET/EGFR treatment completely shut off the signaling. Previously reported cases, as well as those described here, showed only partial and transient sensitivity to anti-MET therapy. The finding that combined anti-MET/EGFR therapy-even in the absence of EGFR genetic alterations-induced complete and durable response, represents a proof of concept and guarantees further investigations, opening a new perspective of treatment for these patients.
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.