ArticleCancer science2012
Establishment of phosphatidylinositol 3-kinase inhibitor-resistant cancer cell lines and therapeutic strategies for overcoming the resistance.
Article in Cancer science, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 19 citations in OpenAlex.
- Insulin receptor substrate 2 (IRS2) confers resistance to PI3K pathway inhibition in PIK3CA mutant breast cancer.The Journal of biological chemistry · 2026Article
- Synergistic effects through targeting the PI3K and IGFR pathways in treating lung cancer carrying activation alterations along the PI3K pathway.Translational oncology · 2026Article
- Cooperative Roles of Class IA PI3K Isoforms in Translocation-Related Sarcoma Cell Survival and Proliferation.Cancer research communications · 2026Article
- ZSTK3744, a Novel Aryl Hydrocarbon Receptor Agonist, Exhibits Efficacy against Chemotherapy-Resistant Triple-Negative Breast Cancer.Cancer research communications · 2026Article
- Role of Insulin-like Growth Factor-1 Receptor in Tobacco Smoking-Associated Lung Cancer Development.Biomedicines · 2024Review
- Subtype-selective induction of apoptosis in translocation-related sarcoma cells induced by PUMA and BIM upon treatment with pan-PI3K inhibitors.Cell death & disease · 2023Article
- Survival and prognosis analyses of concurrent PIK3CA mutations in EGFR mutant non-small cell lung cancer treated with EGFR tyrosine kinase inhibitors.American journal of cancer research · 2021Article
- Inhibition of EphB4-Ephrin-B2 Signaling Enhances Response to Cetuximab-Radiation Therapy in Head and Neck Cancers.Clinical cancer research : an official journal of the American Association for Cancer Research · 2018Article
- Colorectal cancer lung metastasis treatment with polymer-drug nanoparticles.Journal of controlled release : official journal of the Controlled Release Society · 2018Article
- Development and characterisation of a panel of phosphatidylinositide 3-kinase - mammalian target of rapamycin inhibitor resistant lung cancer cell lines.Scientific reports · 2018Article
- Article
- Implications of Insulin-like Growth Factor 1 Receptor Activation in Lung Cancer.The Malaysian journal of medical sciences : MJMS · 2016Review
- Basal expression of insulin-like growth factor 1 receptor determines intrinsic resistance of cancer cells to a phosphatidylinositol 3-kinase inhibitor ZSTK474.Cancer science · 2015Article
- Mechanisms and insights into drug resistance in cancer.Frontiers in pharmacology · 2013Article
- Targeted therapies in development for non-small cell lung cancer.Journal of carcinogenesis · 2013Review
- Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Acquired resistance is a major obstacle for conventional cancer chemotherapy, and also for some of the targeted therapies approved to date. Long-term treatment using protein tyrosine kinase inhibitors (TKIs), such as gefitinib and imatinib, gives rise to resistant cancer cells carrying a drug-resistant gatekeeper mutation in the kinase domain of the respective target genes, EGFR and BCR-ABL. As for the phosphatidylinositol 3-kinase inhibitors (PI3Kis), little is known about their acquired resistance, although some are undergoing clinical trials. To address this issue, we exposed 11 human cancer cell lines to ZSTK474, a PI3Ki we developed previously, for a period of more than 1 year in vitro. Consequently, we established ZSTK474-resistant cells from four of the 11 cancer cell lines tested. The acquired resistance was not only to ZSTK474 but also to other PI3Kis. None of the PI3Ki-resistant cells, however, contained any mutation in the kinase domain of the PIK3CA gene. Instead, we found that insulin-like growth factor 1 receptor (IGF1R) was overexpressed in all four resistant cells. Interestingly, targeted knockdown of IGF1R expression using specific siRNAs or inhibition of IGF1R using IGF1R-TKIs reversed the acquired PI3Ki resistance. These results suggest that long-term treatment with PI3Kis may cause acquired resistance, and targeting IGF1R is a promising strategy to overcome the resistance.
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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.