ArticleScientific reports2018
Wee1 inhibitor MK1775 sensitizes KRAS mutated NSCLC cells to sorafenib.
Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
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Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 28 citations in OpenAlex.
- An update of predictive biomarkers related to WEE1 inhibition in cancer therapy.Journal of cancer research and clinical oncology · 2024Pooled it
- WEE1 inhibitor exerts synergistic effect with KRAS G12C inhibitor via MYBL2-RRM2 axis in KRASCell death & disease · 2025Article
- WEE1 Inhibitor Adavosertib Exerts Antitumor Effects on Colorectal Cancer, Especially in Cases withCancers · 2024Article
- Harnessing lipid metabolism modulation for improved immunotherapy outcomes in lung adenocarcinoma.Journal for immunotherapy of cancer · 2024Article
- Cell cycle checkpoint revolution: targeted therapies in the fight against malignant tumors.Frontiers in pharmacology · 2024Review
- SOX2 expression in prostate cancer drives resistance to nuclear hormone receptor signaling inhibition through the WEE1/CDK1 signaling axis.Cancer letters · 2023Article
- OverexpressedJournal of thoracic disease · 2023Article
- IDO1 Promotes the Progression of NSCLC by Regulating the Polarization of M2 Macrophages.International journal of general medicine · 2023Article
- The current state of the art and future trends in RAS-targeted cancer therapies.Nature reviews. Clinical oncology · 2022Review
- Analysis of the expression, function and signaling of glycogen phosphorylase isoforms in hepatocellular carcinoma.Oncology letters · 2022Article
- DNA Damage Repair Inhibitor for Breast Cancer Treatment.Advances in experimental medicine and biology · 2021Article
- Pharmacological Inhibition of WEE1 Potentiates the Antitumoral Effect of theInternational journal of molecular sciences · 2020Article
- Overcoming acquired resistance of gefitinib in lung cancer cells without T790M by AZD9291 or Twist1 knockdown in vitro and in vivo.Archives of toxicology · 2019Article
- Generation and characterization of MEK and ERK inhibitors- resistant non-small-cells-lung-cancer (NSCLC) cells.BMC cancer · 2018Article
- Knockdown of lncRNA X inactive specific transcript (XIST) radiosensitizes non-small cell lung cancer (NSCLC) cells through regulation of miR-16-5p/WEE1 G2 checkpoint kinase (WEE1) axis.International journal of immunopathology and pharmacologyArticle
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Non-Small-Cell Lung Cancer (NSCLC) is a poorly chemosensitive tumor and targeted therapies are only used for about 15% of patients where a specific driving and druggable lesion is observed (EGFR, ALK, ROS). KRAS is one of the most frequently mutated genes in NSCLC and patients harboring these mutations do not benefit from specific treatments. Sorafenib, a multi-target tyrosine kinase inhibitor, was proposed as a potentially active drug in KRAS-mutated NSCLC patients, but clinical trials results were not conclusive. Here we show that the NSCLC cells' response to sorafenib depends on the type of KRAS mutation. KRAS G12V cells respond less to sorafenib than the wild-type counterpart, in vitro and in vivo. To overcome this resistance, we used high-throughput screening with a siRNA library directed against 719 human kinases, and Wee1 was selected as a sorafenib response modulator. Inhibition of Wee1 by its specific inhibitor MK1775 in combination with sorafenib restored the KRAS mutated cells' response to the multi-target tyrosine kinase inhibitor. This combination of the Wee1 inhibitor with sorafenib, if confirmed in models with different genetic backgrounds, might be worth investigating further as a new strategy for KRAS mutated NSCLC.
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