ArticleJournal of clinical oncology : official journal of the American Society of Clinical Oncology2010
Survival benefit with proapoptotic molecular and pathologic responses from dual targeting of mammalian target of rapamycin and epidermal growth factor receptor in a preclinical model of pancreatic neuroendocrine carcinogenesis.
Article in Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 1 of them a synthesis that pooled it.
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Who cites it
46 citing papers in PubMed, 1 synthesis or guideline pooled it, 97 citations in OpenAlex.
- Efficacy and Safety of Everolimus in Extrapancreatic Neuroendocrine Tumor: A Comprehensive Review of Literature.The oncologist · 2016Pooled it
- An Insight on Functioning Pancreatic Neuroendocrine Neoplasms.Biomedicines · 2023Review
- Article
- METNET: a phase II trial of metformin in patients with well-differentiated neuroendocrine tumours.Ecancermedicalscience · 2022Article
- Cdk5 drives formation of heterogeneous pancreatic neuroendocrine tumors.Oncogenesis · 2021Article
- Review
- Genetic Drivers of Ileal Neuroendocrine Tumors.Cancers · 2021Review
- Cooperation between liver-specific mutations of pten and tp53 genetically induces hepatocarcinogenesis in zebrafish.Journal of experimental & clinical cancer research : CR · 2021Article
- RABL6A Promotes Pancreatic Neuroendocrine Tumor Angiogenesis and Progression In Vivo.Biomedicines · 2021Article
- Review
- Two well-differentiated pancreatic neuroendocrine tumor mouse models.Cell death and differentiation · 2020Article
- Alleles of Insm1 determine whether RIP1-Tag2 mice produce insulinomas or nonfunctioning pancreatic neuroendocrine tumors.Oncogenesis · 2019Article
- Pathway Interactions Based on Drug-Induced Datasets.Cancer informatics · 2019Article
- Consensus guidelines for the use and interpretation of angiogenesis assays.Angiogenesis · 2018Review
- Prognostic and predictive role of the PI3K-AKT-mTOR pathway in neuroendocrine neoplasms.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2018Review
- Dynamic changes during the treatment of pancreatic cancer.Oncotarget · 2018Article
- The Role of mTOR in Neuroendocrine Tumors: Future Cornerstone of a Winning Strategy?International journal of molecular sciences · 2018Review
- Targeted therapy of gastroenteropancreatic neuroendocrine tumours: preclinical strategies and future targets.Endocrine connections · 2018Review
- Therapeutic Benefit of Selective Inhibition of p110α PI3-Kinase in Pancreatic Neuroendocrine Tumors.Clinical cancer research : an official journal of the American Association for Cancer Research · 2016Article
- Sexual dimorphism of liver metastasis by murine pancreatic neuroendocrine tumors is affected by expression of complement C5.Oncotarget · 2016Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposePancreatic neuroendocrine tumors (PNETs), although rare, often metastasize, such that surgery, the only potentially curative therapy, is not possible. There is no effective systemic therapy for patients with advanced PNETs. Therefore, new strategies are needed. Toward that end, we investigated the potential benefit of dual therapeutic targeting of the epidermal growth factor receptor (EGFR) and mammalian target of rapamycin (mTOR) kinases, using a preclinical mouse model of PNET. MATERIALS AND
methodsRapamycin and erlotinib, inhibitors of mTOR and EGFR, respectively, were used to treat RIP-Tag2 transgenic mice bearing advanced multifocal PNET. Tumor growth and survival were monitored, and tumors were surveyed for potential biomarkers of response to the therapeutics.
resultsRapamycin monotherapy was notably efficacious, prolonging survival concomitant with tumor stasis (stable disease). However, the tumors developed resistance, as evidenced by eventual relapse to progressive tumor growth. Erlotinib monotherapy slowed tumor growth and elicited a marginal survival benefit. In combination, there was an unprecedented survival benefit in the face of this aggressive multifocal cancer and, in contrast to either monotherapy, the development of adaptive resistance was not apparent. Additionally, the antiapoptotic protein survivin was implicated as a biomarker of sensitivity and beneficial responses to the dual targeted therapy.
conclusionPreclinical trials in a mouse model of endogenous PNET suggest that combined targeting of the mTOR and EGFR signaling pathways could have potential clinical benefit in treating PNET. These results have encouraged development of an ongoing phase II clinical trial aimed to evaluate the efficacy of this treatment regimen in human neuroendocrine tumors.
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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.