ArticleClinical cancer research : an official journal of the American Association for Cancer Research2012
Common PIK3CA mutants and a novel 3' UTR mutation are associated with increased sensitivity to saracatinib.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
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Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 41 citations in OpenAlex.
- miR in melanoma development: miRNAs and acquired hallmarks of cancer in melanoma.Physiological genomics · 2013Pooled it
- Predictive and prognostic analysis of PIK3CA mutation in stage III colon cancer intergroup trial.Journal of the National Cancer Institute · 2013Trial
- Biomarker-driven trial in metastatic pancreas cancer: feasibility in a multicenter study of saracatinib, an oral Src inhibitor, in previously treated pancreatic cancer.Cancer medicine · 2012Trial
- Upregulation of Sox2 Following Saracatinib Treatment Contributes to a Resistant Phenotype in Colorectal Cancer Cells under Growth Factor-Supplemented Conditions.Oncology research · 2026Article
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- Differential Expression Profiles and Functional Prediction of tRNA-Derived Small RNAs in Rats After Traumatic Spinal Cord Injury.Frontiers in molecular neuroscience · 2019Article
- FIBP knockdown attenuates growth and enhances chemotherapy in colorectal cancer via regulating GSK3β-related pathways.Oncogenesis · 2018Article
- MicroRNAs in the prognosis and therapy of colorectal cancer: From bench to bedside.World journal of gastroenterology · 2018Review
- The novel ATM inhibitor (AZ31) enhances antitumor activity in patient derived xenografts that are resistant to irinotecan monotherapy.Oncotarget · 2017Article
- A tRNA fragment, tRF5-Glu, regulates BCAR3 expression and proliferation in ovarian cancer cells.Oncotarget · 2017Article
- Epigenome Aberrations: Emerging Driving Factors of the Clear Cell Renal Cell Carcinoma.International journal of molecular sciences · 2017Review
- Single nucleotide variant in Nucleoporin 107 may be predictive of sensitivity to chemotherapy in patients with ovarian cancer.Pharmacogenetics and genomics · 2017Article
- Development and Maintenance of a Preclinical Patient Derived Tumor Xenograft Model for the Investigation of Novel Anti-Cancer Therapies.Journal of visualized experiments : JoVE · 2016Article
- MicroRNAs as growth regulators, their function and biomarker status in colorectal cancer.Oncotarget · 2016Review
- Lactate dehydrogenase A negatively regulated by miRNAs promotes aerobic glycolysis and is increased in colorectal cancer.Oncotarget · 2015Article
- MicroRNAs as Regulator of Signaling Networks in Metastatic Colon Cancer.BioMed research international · 2015Review
- The impact of microRNA-mediated PI3K/AKT signaling on epithelial-mesenchymal transition and cancer stemness in endometrial cancer.Journal of translational medicine · 2014Review
- Single nucleotide polymorphisms in microRNA binding sites of oncogenes: implications in cancer and pharmacogenomics.Omics : a journal of integrative biology · 2014Article
- Src mutation induces acquired lapatinib resistance in ERBB2-amplified human gastroesophageal adenocarcinoma models.PloS one · 2014Article
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
Abstract
purposeDysregulation of the phosphoinositide 3-kinase (PI3K) and Src signaling pathways commonly occur in colorectal cancer. Mutations in the PIK3CA gene are associated with an increase in severity of disease and worse clinical outcomes. Elevated levels of Src have been identified in premalignant lesions and are suggested to play a central role in tumor progression. Because these pathways appear to enhance tumor growth and metastasis, molecularly targeted agents for both pathways are currently being evaluated in early-phase clinical trials. EXPERIMENTAL
designWe used colorectal cancer cell lines and a patient-derived explant model to investigate the efficacy of saracatinib. Mutations in the PIK3CA were evaluated to examine the association between mutations in the PIK3CA gene and sensitivity to saracatinib.
resultsWe have identified a subset of patients with a PIK3CA (exon 9 and 20) mutation with increased sensitivity to saracatinib. A novel 3' untranslated region (UTR) mutation was also shown to be associated with increased sensitivity to saracatinib and have a reduced affinity for miR-520a and miR-525a. Importantly, we show that Src inhibition reduces the interaction between Src and p85, subsequently decreasing Akt-dependent signaling.
conclusionThese results indicate that a personalized approach in targeting Src in PIK3CA-mutant patients with colorectal cancers may prove effective in a subset of patients with this genetic alteration.
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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.