ArticleCell death & disease2018
IGF1R upregulation confers resistance to isoform-specific inhibitors of PI3K in PIK3CA-driven ovarian cancer.
Article in Cell death & disease, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 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
30 citing papers in PubMed, 48 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
- The Reproductive Toxicity Valuation of Deoxynivalenol: An Integrated Study from Network Toxicology, Molecular Docking, Molecular Dynamics Simulation and Single-Cell RNA Sequencing.International journal of molecular sciences · 2026Article
- Article
- PTPN9 dephosphorylates IGF1RJournal of experimental & clinical cancer research : CR · 2025Article
- Bta-Let-7d Modulation of Oxidative Stress Induced by Potassium Permanganate in Bovine Endometrial Cells via IGF1R/PI3K/AKT Signaling Pathway.Antioxidants (Basel, Switzerland) · 2025Article
- Protein profiling uncovers IGF-1R inhibition potential of 3-(2-furoyl)-indole scaffolds in hepatocellular carcinoma.Future medicinal chemistry · 2025Article
- Insulin-like Growth Factor 1 (IGF1) and Its Isoforms: Insights into the Mechanisms of Endometrial Cancer.Cancers · 2025Review
- Case Report: Activated PI3-kinase-δ syndrome and ovarian malignancies: a case series from the European ESID-APDS registry.Frontiers in immunology · 2025Article
- Integrative modeling uncovers p21-driven drug resistance and prioritizes therapies for PIK3CA-mutant breast cancer.NPJ precision oncology · 2024Article
- Activation of the EGFR/PI3K/AKT pathway limits the efficacy of trametinib treatment in head and neck cancer.Molecular oncology · 2023Article
- CBF-Beta Mitigates PI3K-Alpha-Specific Inhibitor Killing through PIM1 in PIK3CA-Mutant Gastric Cancer.Molecular cancer research : MCR · 2023Article
- Insulin-like growth factor 1 receptor inhibits the proliferation of acute myeloid leukaemia cells via NK cell activation.Annals of hematology · 2023Article
- IGF-1R down regulates the sensitivity of hepatocellular carcinoma to sorafenib through the PI3K / akt and RAS / raf / ERK signaling pathways.BMC cancer · 2023Article
- Combining radiation with PI3K isoform-selective inhibitor administration increases radiosensitivity and suppresses tumor growth in non-small cell lung cancer.Journal of radiation research · 2022Article
- At a crossroads: how to translate the roles of PI3K in oncogenic and metabolic signalling into improvements in cancer therapy.Nature reviews. Clinical oncology · 2022Review
- Inhibition of autophagy by chloroquine prevents resistance to PI3K/AKT inhibitors and potentiates their antitumor effect in combination with paclitaxel in triple negative breast cancer models.Journal of translational medicine · 2022Article
- Targeting autophagy in disease: established and new strategies.Autophagy · 2022Article
- The deubiquitinase USP8 regulates ovarian cancer cell response to cisplatin by suppressing apoptosis.Frontiers in cell and developmental biology · 2022Article
- Defining the therapeutic selective dependencies for distinct subtypes of PI3K pathway-altered prostate cancers.Nature communications · 2021Article
- Nuclear IGF1R interacts with NuMA and regulates 53BP1‑dependent DNA double‑strand break repair in colorectal cancer.Oncology reports · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Genomic alterations (GA) in PIK3CA leads to the hyper-activation of the phosphatidylinositol-4, 5-bisphosphate 3-kinase (PI3K) pathway in more than 20% of ovarian cancer (OC) patients. Therefore, PI3K therapies are under clinical evaluation for this subset of patients. Evidently, in clinical trials testing the efficacy of isoform-specific inhibitors of PI3K (PI3Ki), patients having a stable disease eventually relapse, as tumors become resistant to treatment. Hence, there is an urgent clinical need to develop new therapeutic combinations to improve the efficacy of PI3Ki in PIK3CA-driven OC patients. Here we identified the molecular mechanism that limits the efficacy of the beta-sparing PI3Ki, Taselisib (GDC0032), in PIK3CA-mutated OC cell lines (IGROV1 and OAW42) that acquired resistance to GDC0032. By comparing the molecular profile of GDC0032-sensitve and -resistant OC cell lines, we found that AKT/mTOR inhibition is required for GDC0032 efficacy. In resistant cells, the sustained activation of AKT/mTOR was regulated by the upregulation of the insulin growth factor 1 receptor (IGF1R). Knockdown of IGF1R re-sensitized cells to GDC0032 in vitro, and the combination of AEW541, an IGF1R inhibitor, with GDC0032 exhibited potent anti-tumor activity in vitro and in vivo. We further demonstrated that IGF1R regulates tumor cell proliferation in IGROV1 cells, whereas in OAW42, it determines autophagy as well. Overall, our findings suggest that the dual inhibition of PI3K and IGF1R may be considered as a new therapeutic strategy in PIK3CA-driven OC.
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.