ArticleEndocrinology2019
Synergistic Highly Potent Targeted Drug Combinations in Different Pheochromocytoma Models Including Human Tumor Cultures.
Article in Endocrinology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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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
25 citing papers in PubMed, 41 citations in OpenAlex.
- Phase II Study of ONC201 in Neuroendocrine Tumors including Pheochromocytoma-Paraganglioma and Desmoplastic Small Round Cell Tumor.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022Trial
- Personalized Drug Screening and Risk Assessment in Patient-Derived Gastroenteropancreatic Neuroendocrine Neoplasms.The Journal of clinical endocrinology and metabolism · 2026Article
- Long-term culture of patient-derived pheochromocytoma organoids.Frontiers in endocrinology · 2026Article
- Approach to the Patient With Metastatic Pheochromocytoma and Paraganglioma.The Journal of clinical endocrinology and metabolism · 2025Article
- Combinatorial screen of targeted agents with the PI3K inhibitors inavolisib, alpelisib, duvelisib, and copanlisib in multi-cell type tumor spheroids.SLAS discovery : advancing life sciences R & D · 2025Article
- Paltusotine versus octreotide: different effects on radioligand uptake in neuroendocrine tumours.Endocrine oncology (Bristol, England) · 2025Article
- Opposing Effects of Cannabidiol in Patient-derived Neuroendocrine Tumor, Pheochromocytoma/Paraganglioma Primary Cultures.The Journal of clinical endocrinology and metabolism · 2024Article
- Bioengineered in vitro three-dimensional tumor models in endocrine cancers.Endocrine-related cancer · 2024Review
- The Management of Phaeochromocytomas and Paragangliomas in the Era of Precision Medicine: Where Are We Now? Evidence-Based Systemic Treatment Options and Future Cluster Oriented Perspectives.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Tumor metabolism in pheochromocytomas: clinical and therapeutic implications.Exploration of targeted anti-tumor therapy · 2024Review
- Improving susceptibility of neuroendocrine tumors to radionuclide therapies: personalized approaches towards complementary treatments.Theranostics · 2024Review
- Three Dimensional Models of Endocrine Organs and Target Tissues Regulated by the Endocrine System.Cancers · 2023Review
- Targeted Therapies in Pheochromocytoma and Paraganglioma.The Journal of clinical endocrinology and metabolism · 2022Review
- Management of Pheochromocytomas and Paragangliomas: A Case-Based Review of Clinical Aspects and Perspectives.Journal of clinical medicine · 2022Review
- Personalized Management of Pheochromocytoma and Paraganglioma.Endocrine reviews · 2022Review
- Treatment of Pheochromocytoma Cells with Recurrent Cycles of Hypoxia: A New Pseudohypoxic In Vitro Model.Cells · 2022Article
- New Insights on the Genetics of Pheochromocytoma and Paraganglioma and Its Clinical Implications.Cancers · 2022Review
- Model systems in SDHx-related pheochromocytoma/paraganglioma.Cancer metastasis reviews · 2021Review
- The role of regulated necrosis in endocrine diseases.Nature reviews. Endocrinology · 2021Review
- Plasma Metabolome Profiling for the Diagnosis of Catecholamine Producing Tumors.Frontiers in endocrinology · 2021Article
Corrections and comments
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Authors and funding
26 authors at 10 institutions in 6 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
There are no officially approved therapies for metastatic pheochromocytomas apart from ultratrace 131I-metaiodbenzylguanidine therapy, which is approved only in the United States. We have, therefore, investigated the antitumor potential of molecular-targeted approaches in murine pheochromocytoma cell lines [monocyte chemoattractant protein (MPC)/monocyte chemoattractant protein/3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)], immortalized mouse chromaffin Sdhb-/- cells, three-dimensional pheochromocytoma tumor models (MPC/MTT spheroids), and human pheochromocytoma primary cultures. We identified the specific phosphatidylinositol-3-kinase α inhibitor BYL719 and the mammalian target of rapamycin inhibitor everolimus as the most effective combination in all models. Single treatment with clinically relevant doses of BYL719 and everolimus significantly decreased MPC/MTT and Sdhb-/- cell viability. A targeted combination of both inhibitors synergistically reduced MPC and Sdhb-/- cell viability and showed an additive effect on MTT cells. In MPC/MTT spheroids, treatment with clinically relevant doses of BYL719 alone or in combination with everolimus was highly effective, leading to a significant shrinkage or even a complete collapse of the spheroids. We confirmed the synergism of clinically relevant doses of BYL719 plus everolimus in human pheochromocytoma primary cultures of individual patient tumors with BYL719 attenuating everolimus-induced AKT activation. We have thus established a method to assess molecular-targeted therapies in human pheochromocytoma cultures and identified a highly effective combination therapy. Our data pave the way to customized combination therapy to target individual patient 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.