ArticleCancer research2011
MET-independent lung cancer cells evading EGFR kinase inhibitors are therapeutically susceptible to BH3 mimetic agents.
Article in Cancer research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 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
47 citing papers in PubMed, 79 citations in OpenAlex.
- The sleeping threat: targeting cancer dormancy to transform metastasis therapy.Nature reviews. Cancer · 2026Review
- Unmasking the common enemy: drug resistance mechanisms across three different EGFR inhibitor generations are associated with co-targetable alterations in extracellular matrix signaling.Cell communication and signaling : CCS · 2026Article
- Revealing the landscape of targeting mitochondrial functions and behaviors to overcome cancer chemoresistance.Journal of the National Cancer Center · 2025Review
- Drug tolerant persister cell plasticity in cancer: A revolutionary strategy for more effective anticancer therapies.Signal transduction and targeted therapy · 2024Review
- ASCL1 Drives Tolerance to Osimertinib in EGFR Mutant Lung Cancer in Permissive Cellular Contexts.Cancer research · 2024Article
- The Resistance to EGFR-TKIs in Non-Small Cell Lung Cancer: From Molecular Mechanisms to Clinical Application of New Therapeutic Strategies.Pharmaceutics · 2023Review
- Characteristics and molecular mechanism of drug-tolerant cells in cancer: a review.Frontiers in oncology · 2023Review
- The genomic and immune landscape of long-term survivors of high-grade serous ovarian cancer.Nature genetics · 2022Article
- Integration of liquid biopsy and pharmacogenomics for precision therapy of EGFR mutant and resistant lung cancers.Molecular cancer · 2022Review
- Tumor Dormancy: Biologic and Therapeutic Implications.World journal of oncology · 2022Review
- The manipulation of apoptosis for cancer therapy using BH3-mimetic drugs.Nature reviews. Cancer · 2022Review
- Comprehensive targeting of resistance to inhibition of RTK signaling pathways by using glucocorticoids.Nature communications · 2021Article
- Coregulation of pathways in lung cancer patients with EGFR mutation: therapeutic opportunities.British journal of cancer · 2021Review
- Review
- When to wake up? The optimal waking-up strategies for starvation-induced persistence.PLoS computational biology · 2021Article
- Frontiers of ctDNA, targeted therapies, and immunotherapy in non-small-cell lung cancer.Translational lung cancer research · 2020Review
- The Role of the ECM in Lung Cancer Dormancy and Outgrowth.Frontiers in oncology · 2020Review
- Emerging insights of tumor heterogeneity and drug resistance mechanisms in lung cancer targeted therapy.Journal of hematology & oncology · 2019Review
- Metabolic Plasticity and Epithelial-Mesenchymal Transition.Journal of clinical medicine · 2019Review
- Prospective analysis of liquid biopsies of advanced non-small cell lung cancer patients after progression to targeted therapies using GeneReader NGS platform.Translational cancer research · 2019Article
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 5 institutions in 1 country.
Funding
Abstract
Targeted therapies for cancer are inherently limited by the inevitable recurrence of resistant disease after initial responses. To define early molecular changes within residual tumor cells that persist after treatment, we analyzed drug-sensitive lung adenocarcinoma cell lines exposed to reversible or irreversible epidermal growth factor receptor (EGFR) inhibitors, alone or in combination with MET-kinase inhibitors, to characterize the adaptive response that engenders drug resistance. Tumor cells displaying early resistance exhibited dependence on MET-independent activation of BCL-2/BCL-XL survival signaling. Further, such cells displayed a quiescence-like state associated with greatly retarded cell proliferation and cytoskeletal functions that were readily reversed after withdrawal of targeted inhibitors. Findings were validated in a xenograft model, showing BCL-2 induction and p-STAT3[Y705] activation within the residual tumor cells surviving the initial antitumor response to targeted therapies. Disrupting the mitochondrial BCL-2/BCL-XL antiapoptotic machinery in early survivor cells using BCL-2 Homology Domain 3 (BH3) mimetic agents such as ABT-737, or by dual RNAi-mediated knockdown of BCL-2/BCL-XL, was sufficient to eradicate the early-resistant lung-tumor-cells evading targeted inhibitors. Similarly, in a xenograft model the preemptive cotreatment of lung tumor cells with an EGFR inhibitor and a BH3 mimetic eradicated early TKI-resistant evaders and ultimately achieved a more durable response with prolonged remission. Our findings prompt prospective clinical investigations using BH3-mimetics combined with targeted receptor kinase inhibitors to optimize and improve clinical outcomes in lung-cancer treatment.
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.