ArticleOncotarget2014
Combining AKT inhibition with chloroquine and gefitinib prevents compensatory autophagy and induces cell death in EGFR mutated NSCLC cells.
Article in Oncotarget, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07486648 (The Safety and Efficacy of Osimertinib Plus Capivasertib in EGFRm Advanced Non-small Cell Lung Cancer), which is not on this map. Cited by 34 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.
The Safety and Efficacy of Osimertinib Plus Capivasertib in EGFRm Advanced Non-small Cell Lung Cancer (NSCLC) Participants With PIK3CA/AKT1/PTEN Alterations Who Had Progressed on First-line Osimertinib Monotherapy or Plus Chemotherapy: a First-in-human, Phase Ib/Ⅱa Study (PRECISION)
Who cites it
34 citing papers in PubMed, 46 citations in OpenAlex.
- Multi-Target Antitumor Effects of Natural Products and Approved Drug Repurposing in Non-Small Cell Lung Cancer: Advances in Mechanisms, Combination Regimens, Delivery System Optimization, and Clinical Challenges.International journal of molecular sciences · 2026Review
- SynProtX: a large-scale proteomics-based deep learning model for predicting synergistic anticancer drug combinations.GigaScience · 2025Article
- Antipsychotics possess anti-glioblastoma activity by disrupting lysosomal function and inhibiting oncogenic signaling by stabilizing PTEN.Cell death & disease · 2024Article
- Tumor-associated macrophages mediate resistance of EGFR-TKIs in non-small cell lung cancer: mechanisms and prospects.Frontiers in immunology · 2023Review
- Article
- Hypoxia signaling in human health and diseases: implications and prospects for therapeutics.Signal transduction and targeted therapy · 2022Review
- Emerging Role of Autophagy in the Development and Progression of Oral Squamous Cell Carcinoma.Cancers · 2021Review
- Clinical Development of AKT Inhibitors and Associated Predictive Biomarkers to Guide Patient Treatment in Cancer Medicine.Pharmacogenomics and personalized medicine · 2021Review
- Proliferation of Lung Epithelial Cells Is Regulated by the Mechanisms of Autophagy Upon Exposure of Soots.Frontiers in cell and developmental biology · 2021Article
- Role of PARP1-mediated autophagy in EGFR-TKI resistance in non-small cell lung cancer.Scientific reports · 2020Article
- Review
- PAQR3 suppresses the growth of non-small cell lung cancer cells via modulation of EGFR-mediated autophagy.Autophagy · 2020Article
- Mechanism of Xu Li's Experiential Prescription for the Treatment of EGFR-Positive NSCLC.Evidence-based complementary and alternative medicine : eCAM · 2020Article
- FAM83A signaling induces epithelial-mesenchymal transition by the PI3K/AKT/Snail pathway in NSCLC.Aging · 2019Article
- Sequence-dependent synergistic cytotoxicity of icotinib and pemetrexed in human lung cancer cell lines in vitro and in vivo.Journal of experimental & clinical cancer research : CR · 2019Article
- LAPTM4B knockdown increases the radiosensitivity of EGFR-overexpressing radioresistant nasopharyngeal cancer cells by inhibiting autophagy.OncoTargets and therapy · 2019Article
- Gefitinib induces non-small cell lung cancer H1650 cell apoptosis through downregulating tumor necrosis factor-related apoptosis-inducing ligand expression levels.Oncology letters · 2018Article
- In vitro and in vivo effects of MK2206 and chloroquine combination therapy on endometriosis: autophagy may be required for regrowth of endometriosis.British journal of pharmacology · 2018Article
- Novel 3D Liquid Cell Culture Method for Anchorage-independent Cell Growth, Cell Imaging and Automated Drug Screening.Scientific reports · 2018Article
- Development and Evaluation ofScientific reports · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Although non-small cell lung cancer (NSCLC) patients with EGFR mutation positive (EGFR M+) tumors initially respond well to EGFR tyrosine kinase inhibitor (TKI) monotherapy, the responses are usually incomplete. In this study we show that AKT inhibition, most importantly AKT2 inhibition, synergises with EGFR TKI inhibition to increase cell killing in EGFR M+ NSCLC cells. However, our data also suggest that the synergistic pro-apoptotic effects may be stunted due to a prosurvival autophagy response induced by AKT inhibition. Consequently, inhibiting autophagy with chloroquine significantly enhanced tumor cell death induced by gefitinib and AKT inhibitors in EGFR M+ cells in vitro, and produced greater tumor shrinkage in EGFR M+ xenografts in vivo. Together, our findings suggest that adding chloroquine to EGFR and AKT inhibition has the potential to improve tumor responses in EGFR M+ NSCLC, and that selective targeting of AKT2 may provide a new treatment option in NSCLC.
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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.