ArticleBMC cancer2015
Suppression of Homologous Recombination by insulin-like growth factor-1 inhibition sensitizes cancer cells to PARP inhibitors.
Article in BMC cancer, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 30 citations in OpenAlex.
- PARP inhibitors target cellular energy metabolism: Mechanisms of action and clinical implications.Translational oncology · 2026Review
- Loss of IGF-1R impairs DNA-PKcs recruitment to chromatin leading to defective end-joining.Molecular oncology · 2026Article
- IGF-1R inhibitors in cancer: A review of available evidence and future outlook.Critical reviews in oncology/hematology · 2025Review
- Review
- Biomarkers beyond BRCA: promising combinatorial treatment strategies in overcoming resistance to PARP inhibitors.Journal of biomedical science · 2022Review
- The Role of ARID1A in the Nonestrogenic Modulation of IGF-1 Signaling.Molecular cancer research : MCR · 2022Article
- Article
- PARP inhibitors in gastric cancer: beacon of hope.Journal of experimental & clinical cancer research : CR · 2021Review
- Synergistic effects of type I PRMT and PARP inhibitors against non-small cell lung cancer cells.Clinical epigenetics · 2021Article
- Antitumor effect of a WEE1 inhibitor and potentiation of olaparib sensitivity by DNA damage response modulation in triple-negative breast cancer.Scientific reports · 2020Article
- The role of ADP-ribose metabolism in metabolic regulation, adipose tissue differentiation, and metabolism.Genes & development · 2020Review
- Biguanides in combination with olaparib limits tumorigenesis of drug-resistant ovarian cancer cells through inhibition of Snail.Cancer medicine · 2020Article
- Nuclear IGF1R interact with PCNA to preserve DNA replication after DNA-damage in a variety of human cancers.PloS one · 2020Article
- Article
- Prospect for Application of PARP Inhibitor in Patients with HER2 Negative Breast Cancer.International journal of biological sciences · 2019Review
- Augmented antitumor activity by olaparib plus AZD1775 in gastric cancer through disrupting DNA damage repair pathways and DNA damage checkpoint.Journal of experimental & clinical cancer research : CR · 2018Article
- Update on PARP Inhibitors in Breast Cancer.Current treatment options in oncology · 2018Review
- Insulin-Like Growth Factor (IGF) Pathway Targeting in Cancer: Role of the IGF Axis and Opportunities for Future Combination Studies.Targeted oncology · 2017Review
- Inhibition of PI3K-AKT-mTOR pathway sensitizes endometrial cancer cell lines to PARP inhibitors.BMC cancer · 2017Article
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
backgroundImpairment of homologous recombination (HR) is found in close to 50 % of ovarian and breast cancer. Tumors with BRCA1 mutations show increased expression of the Insulin-like growth factor type 1 receptor (IGF-1R). We previously have shown that inhibition of IGF-1R results in growth inhibition and apoptosis of ovarian tumor cells. In the current study, we aimed to investigate the correlation between HR and sensitivity to IGF-1R inhibition. Further, we hypothesized that IGF-1R inhibition might sensitize HR proficient cancers to Poly ADP ribose polymerase (PARP) inhibitors.
methodsUsing ovarian and breast cancer cellular models with known BRCA1 status, we evaluated their HR functionality by RAD51 foci formation assay. The 50 % lethal concentration (LC50) of Insulin-like growth factor type 1 receptor kinase inhibitor (IGF-1Rki) in these cells was assessed, and western immunoblotting was performed to determine the expression of proteins involved in the IGF-1R pathway. Moreover, IGF-1R inhibitors were added on HR proficient cell lines to assess mRNA and protein expression of RAD51 by qPCR and western blot. Also, we explored the interaction between RAD51 and Insulin receptor substance 1 (IRS-1) by immunoprecipitation. Next, combination effect of IGF-1R and PARP inhibitors was evaluated by clonogenic assay.
resultsCells with mutated/methylated BRCA1 showed an impaired HR function, and had an overactivation of the IGF-1R pathway. These cells were more sensitive to IGF-1R inhibition compared to HR proficient cells. In addition, the IGF-IR inhibitor reduced RAD51 expression at mRNA and protein levels in HR proficient cells, and sensitized these cells to PARP inhibitor.
conclusionTargeting IGF-1R might lead to improved personalized therapeutic approaches in cancer patients with HR deficiency. Targeting both PARP and IGF-1R might increase the clinical efficacy in HR deficient patients and increase the population of patients who may benefit from PARP inhibitors.
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