ArticleCancer research2017
Adaptation to TKI Treatment Reactivates ERK Signaling in Tyrosine Kinase-Driven Leukemias and Other Malignancies.
Article in Cancer research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
What it found
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Who cites it
32 citing papers in PubMed, 43 citations in OpenAlex.
- ATO alleviates T-cell immunosuppression by inducing apoptosis-associated secretion of IL-2 in FLT3-ITD-mutated acute myeloid leukemia.Translational oncology · 2026Article
- Sphingosine-1-phosphate receptor modulators resensitize FLT3-ITD acute myeloid leukemia cells with NRAS mutations to FLT3 inhibitors.Leukemia · 2026Article
- Role of signaling pathways in lung cancer development and advances in targeted therapies (Review).Oncology letters · 2025Review
- Targeting rapid TKI-induced AXL upregulation overcomes adaptive ERK reactivation and exerts antileukemic effects in FLT3/ITD acute myeloid leukemia.Molecular oncology · 2025Article
- Cytokine-mediated CAR T therapy resistance in AML.Nature medicine · 2024Article
- Inhibition of NOTCH4 sensitizes FLT3/ITD acute myeloid leukemia cells to FLT3 tyrosine kinase inhibition.Leukemia · 2024Article
- FLT3 tyrosine kinase inhibition modulates PRC2 and promotes differentiation in acute myeloid leukemia.Leukemia · 2024Article
- Overcoming adaptive resistance in AML by synergistically targeting FOXO3A-GNG7-mTOR axis with FOXO3A inhibitor Gardenoside and rapamycin.Genes & diseases · 2024Article
- Mediating kinase activity in Ras-mutant cancer: potential for an individualised approach?Frontiers in pharmacology · 2024Review
- Allosteric SHP2 inhibition increases apoptotic dependency on BCL2 and synergizes with venetoclax in FLT3- and KIT-mutant AML.Cell reports. Medicine · 2023Article
- Venetoclax Overcomes Sorafenib Resistance in Acute Myeloid Leukemia by Targeting BCL2.Biology · 2023Article
- CombinationThyroid : official journal of the American Thyroid Association · 2023Article
- Combining Multikinase Tyrosine Kinase Inhibitors Targeting the Vascular Endothelial Growth Factor and Cluster of Differentiation 47 Signaling Pathways Is Predicted to Increase the Efficacy of Antiangiogenic Combination Therapies.ACS pharmacology & translational science · 2023Article
- Dual inhibition of CHK1/FLT3 enhances cytotoxicity and overcomes adaptive and acquired resistance in FLT3-ITD acute myeloid leukemia.Leukemia · 2023Article
- Article
- Translatome proteomics identifies autophagy as a resistance mechanism to on-target FLT3 inhibitors in acute myeloid leukemia.Leukemia · 2022Article
- The Irreversible FLT3 Inhibitor FF-10101 Is Active Against a Diversity of FLT3 Inhibitor Resistance Mechanisms.Molecular cancer therapeutics · 2022Article
- Genome-wide CRISPR screen identifies regulators of MAPK and MTOR pathways mediating sorafenib resistance in acute myeloid leukemia.Haematologica · 2022Article
- Article
- FLT3 tyrosine kinase inhibitors synergize with BCL-2 inhibition to eliminate FLT3/ITD acute leukemia cells through BIM activation.Signal transduction and targeted therapy · 2021Article
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
FMS-like tyrosine kinase-3 (FLT3) tyrosine kinase inhibitors (TKI) have been tested extensively to limited benefit in acute myeloid leukemia (AML). We hypothesized that FLT3/internal tandem duplication (ITD) leukemia cells exhibit mechanisms of intrinsic signaling adaptation to TKI treatment that are associated with an incomplete response. Here, we identified reactivation of ERK signaling within hours following treatment of FLT3/ITD AML cells with selective inhibitors of FLT3. When these cells were treated with inhibitors of both FLT3 and MEK in combination, ERK reactivation was abrogated and anti-leukemia effects were more pronounced compared with either drug alone. ERK reactivation was also observed following inhibition of other tyrosine kinase-driven cancer cells, including EGFR-mutant lung cancer, HER2-amplified breast cancer, and BCR-ABL leukemia. These studies reveal an adaptive feedback mechanism in tyrosine kinase-driven cancers associated with reactivation of ERK signaling in response to targeted inhibition.
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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.