ArticlePloS one2017
The selective PI3Kα inhibitor BYL719 as a novel therapeutic option for neuroendocrine tumors: Results from multiple cell line models.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 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
20 citing papers in PubMed, 34 citations in OpenAlex.
- Personalized Drug Screening and Risk Assessment in Patient-Derived Gastroenteropancreatic Neuroendocrine Neoplasms.The Journal of clinical endocrinology and metabolism · 2026Article
- GSK3i combinatorial treatments affect CDK4/6 and compensatory pathways in 3D preclinical models of pancreatic neuroendocrine tumors.Biology open · 2026Article
- 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
- A case report: enhanced somatostatin receptor expression in metastatic pancreatic neuroendocrine tumor following everolimus therapy.Frontiers in cell and developmental biology · 2025Article
- Improving susceptibility of neuroendocrine tumors to radionuclide therapies: personalized approaches towards complementary treatments.Theranostics · 2024Review
- Concomitant inhibition of PI3K/mTOR signaling pathways boosts antiproliferative effects of lanreotide in bronchopulmonary neuroendocrine tumor cells.Frontiers in pharmacology · 2024Article
- Carcinoid Syndrome: Preclinical Models and Future Therapeutic Strategies.International journal of molecular sciences · 2023Review
- Dual inhibition of atypical PKC signaling and PI3K/Akt signaling dysregulates c-Myc to induce apoptosis in clear cell Renal Cell Carcinoma.Frontiers in oncology · 2023Article
- Article
- Lysosomal Changes in Mitosis.Cells · 2022Article
- Overexpression of somatostatin receptor type 2 in neuroendocrine tumors for improved Ga68-DOTATATE imaging and treatment.Surgery · 2020Article
- Synergistic Highly Potent Targeted Drug Combinations in Different Pheochromocytoma Models Including Human Tumor Cultures.Endocrinology · 2019Article
- Simultaneous inhibition of PI3Kα and CDK4/6 synergistically suppresses KRAS-mutated non-small cell lung cancer.Cancer biology & medicine · 2019Article
- Article
- Molecular features and translational outlook for Epstein-Barr virus-associated gastric cancer.Future virology · 2018Article
- The role of GSK3 and its reversal with GSK3 antagonism in everolimus resistance.Endocrine-related cancer · 2018Article
- Co-administration of iRGD with peptide HPRP-A1 to improve anticancer activity and membrane penetrability.Scientific reports · 2018Article
- Article
- Targeted therapy of gastroenteropancreatic neuroendocrine tumours: preclinical strategies and future targets.Endocrine connections · 2018Review
- Everolimus-induced somatostatin receptor overexpression in a rectal neuroendocrine tumor patient may promote somatostatin receptor-guided radionuclide therapy (peptide receptor radiotherapy) as an additional treatment option.World journal of nuclear medicineArticle
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
18 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND/
aimsThe therapeutic options for metastatic neuroendocrine tumors (NETs) are limited. As PI3K signaling is often activated in NETs, we have assessed the effects of selective PI3Kp110α inhibition by the novel agent BYL719 on cell viability, colony formation, apoptosis, cell cycle, signaling pathways, differentiation and secretion in pancreatic (BON-1, QGP-1) and pulmonary (H727) NET cell lines.
methodsCell viability was investigated by WST-1 assay, colony formation by clonogenic assay, apoptosis by caspase3/7 assay, the cell cycle by FACS, cell signaling by Western blot analysis, expression of chromogranin A and somatostatin receptors 1/2/5 by RT-qPCR, and chromogranin A secretion by ELISA.
resultsBYL719 dose-dependently decreased cell viability and colony formation with the highest sensitivity in BON-1, followed by H727, and lowest sensitivity in QGP-1 cells. BYL719 induced apoptosis and G0/G1 cell cycle arrest associated with increased p27 expression. Western blots showed inhibition of PI3K downstream targets to a varying degree in the different cell lines, but IGF1R activation. The most sensitive BON-1 cells displayed a significant, and H727 cells a non-significant, GSK3 inhibition after BYL719 treatment, but these effects do not appear to be mediated through the IGF1R. In contrast, the most resistant QGP-1 cells showed no GSK3 inhibition, but a modest activation, which would partially counteract the other anti-proliferative effects. Accordingly, BYL719 enhanced neuroendocrine differentiation with the strongest effect in BON-1, followed by H727 cells indicated by induction of chromogranin A and somatostatin receptor 1/2 mRNA-synthesis, but not in QGP-1 cells. In BON-1 and QGP-1 cells, the BYL719/everolimus combination was synergistic through simultaneous AKT/mTORC1 inhibition, and significantly increased somatostatin receptor 2 transcription compared to each drug separately.
conclusionOur results suggest that the agent BYL719 could be a novel therapeutic approach to the treatment of NETs that may sensitize NET cells to somatostatin analogs, and that if there is resistance to its action this may be overcome by combination with everolimus.
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.