ArticleOncotarget2015
Mutant HRAS as novel target for MEK and mTOR inhibitors.
Article in Oncotarget, 2015. 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
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Who cites it
30 citing papers in PubMed, 59 citations in OpenAlex.
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- Tiered Group of Disease Driven Oncogene Informs Survival Outcome of Taiwanese and Japanese Patients with Advanced NSCLC in the LC-SCRUM-Asia Study.Lung Cancer (Auckland, N.Z.) · 2026Article
- IκBα kinase inhibitor BAY 11-7082 promotes anti-tumor effect in RAS-driven cancers.Journal of translational medicine · 2024Article
- NPRL2 is required for proliferation of oncogenic Ras-transformed bronchial epithelial cells.Cell division · 2024Article
- Article
- Functional proteomics of patient derived head and neck squamous cell carcinoma cells reveal novel applications of trametinib.Cancer biology & therapy · 2022Article
- HRAS Q61L Mutation as a Possible Target for Non-Small Cell Lung Cancer: Case Series and Review of Literature.Current oncology (Toronto, Ont.) · 2022Review
- Article
- Potential of Farnesyl Transferase Inhibitors in Combination Regimens in Squamous Cell Carcinomas.Cancers · 2021Article
- BRAP2 inhibits the Ras/Raf/MEK and PI3K/Akt pathways in leukemia cells, thereby inducing apoptosis and inhibiting cell growth.Experimental and therapeutic medicine · 2021Article
- Genomic and pathological heterogeneity in clinically diagnosed small cell lung cancer in never/light smokers identifies therapeutically targetable alterations.Molecular oncology · 2021Article
- Poor Prognosis of Pulmonary Adenosquamous Carcinoma withOncoTargets and therapy · 2021Article
- MEK is a promising target in the basal subtype of bladder cancer.Oncotarget · 2020Article
- Adenomyoepithelial tumors of the breast: molecular underpinnings of a rare entity.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2020Article
- Tipifarnib as a Precision Therapy forMolecular cancer therapeutics · 2020Article
- Ex vivo assessment of targeted therapies in a rare metastatic epithelial-myoepithelial carcinoma.Neoplasia (New York, N.Y.) · 2020Article
- Capturing the primordial Kras mutation initiating urethane carcinogenesis.Nature communications · 2020Article
- The paradox of cancer genes in non-malignant conditions: implications for precision medicine.Genome medicine · 2020Review
- LEF1/Id3/HRAS axis promotes the tumorigenesis and progression of esophageal squamous cell carcinoma.International journal of biological sciences · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
HRAS is a frequently mutated oncogene in cancer. However, mutant HRAS as drug target has not been investigated so far. Here, we show that mutant HRAS hyperactivates the RAS and the mTOR pathway in various cancer cell lines including lung, bladder and esophageal cancer. HRAS mutation sensitized toward growth inhibition by the MEK inhibitors AZD6244, MEK162 and PD0325901. Further, we found that MEK inhibitors induce apoptosis in mutant HRAS cell lines but not in cell lines lacking RAS mutations. In addition, knockdown of HRAS by siRNA blocked cell growth in mutant HRAS cell lines. Inhibition of the PI3K pathway alone or in combination with MEK inhibitors did not alter signaling nor had an impact on viability. However, inhibition of mTOR or combined inhibition of MEK and mTOR reduced cell growth in a synergistic manner. Finally, Ba/F3 cells transformed with mutant HRAS isoforms Q61L, Q61R and G12V demonstrated equal sensitivity towards MEK and mTOR inhibition. Our results show that HRAS mutations in cancer activate the RAS and mTOR pathways which might serve as a therapeutic option for patients with HRAS mutant tumors.
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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.