ArticleClinical cancer research : an official journal of the American Association for Cancer Research2013
The Janus kinases inhibitor AZD1480 attenuates growth of small cell lung cancers in vitro and in vivo.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 24 citations in OpenAlex.
- Direct and indirect effects of IFN-α2b in malignancy treatment: not only an archer but also an arrow.Biomarker research · 2022Review
- Inhibition of Janus Kinase 1 synergizes docetaxel sensitivity in prostate cancer cells.Journal of cellular and molecular medicine · 2021Article
- Characterization of epidermal growth factor receptor (EGFR) P848L, an unusual EGFR variant present in lung cancer patients, in a murine Ba/F3 model.FEBS open bio · 2019Article
- [Research Advances of JAK/STAT Signaling Pathway in Lung Cancer].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2019Review
- Article
- Targeting the IL-6/JAK/STAT3 signalling axis in cancer.Nature reviews. Clinical oncology · 2018Review
- Inhibitor repurposing reveals ALK, LTK, FGFR, RET and TRK kinases as the targets of AZD1480.Oncotarget · 2017Article
- Janus Kinase 2 (JAK2) Dissociates Hepatosteatosis from Hepatocellular Carcinoma in Mice.The Journal of biological chemistry · 2017Article
- MEDICI: Mining Essentiality Data to Identify Critical Interactions for Cancer Drug Target Discovery and Development.PloS one · 2017Article
- Small Cell Lung Cancer: Can Recent Advances in Biology and Molecular Biology Be Translated into Improved Outcomes?Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2016Review
- JAK2 inhibition sensitizes resistant EGFR-mutant lung adenocarcinoma to tyrosine kinase inhibitors.Science signaling · 2016Article
- Emerging cytokine networks in colorectal cancer.Nature reviews. Immunology · 2015Review
- Targeted Blockade of JAK/STAT3 Signaling Inhibits Ovarian Carcinoma Growth.Molecular cancer therapeutics · 2015Article
- JAK kinase inhibition abrogates STAT3 activation and head and neck squamous cell carcinoma tumor growth.Neoplasia (New York, N.Y.) · 2015Article
- Poly (ADP) ribose polymerase enzyme inhibitor, veliparib, potentiates chemotherapy and radiation in vitro and in vivo in small cell lung cancer.Cancer medicine · 2014Article
- Initial solid tumor testing (stage 1) of AZD1480, an inhibitor of Janus kinases 1 and 2 by the pediatric preclinical testing program.Pediatric blood & cancer · 2014Article
- Protein kinase small molecule inhibitors for rheumatoid arthritis: Medicinal chemistry/clinical perspectives.World journal of orthopedics · 2014Review
- Role of STAT3 in lung cancer.JAK-STAT · 2014Review
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
Abstract
purposeThe prognosis of small cell lung cancer (SCLC) is poor, and there has been very little progress in the medical treatment of SCLC in the past two decades. We investigated the potential of Janus-activated kinases (JAK) inhibitor, AZD1480, for treatment of SCLC in vitro and in vivo. EXPERIMENTAL
designJAK1 and JAK2 were inhibited by AZD1480 or siRNAs, and the effect of inhibition of JAK gene family on SCLC cell viability was evaluated. The effect of AZD1480 on cell-cycle distribution and apoptosis induction was studied. Antitumor effects of AZD1480 in tumor xenografts were assessed.
resultsAZD1480 significantly inhibited growth of six out of 13 SCLC cells with IC50s ranging from 0.73 to 3.08 μmol/L. Knocking down of JAK2 and JAK1 inhibited proliferation of Jak2-positive/Jak1-negative H82 cells and Jak1-positive/Jak2-negative GLC4 cells, respectively. Treatment of SCLC cells with AZD1480 for 24 hours resulted in an increase of 4N DNA content and histone 3 serine 10 phosphorylation, indicative of G2-M phase arrest. Moreover, SCLCs underwent apoptosis after AZD1480 treatment as exemplified by the downregulation of MCL1, the accumulation of cleaved caspase 3, cleaved PARP, and increase of annexin-V-positive cells. Finally, xenograft experiments showed that AZD1480 attenuated the growth of H82 and GLC4 tumors in mice, and we observed stronger apoptosis as well as decreased CD31-positive endothelial cells in H82 and GLC4 xenografts upon AZD1480 treatment.
conclusionsJAK inhibitor AZD1480 attenuated growth of SCLC cells in vitro and in vivo. Clinical development of anti-JAKs therapies in SCLC warrants further investigation.
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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.