MA11.01 Development of Novel EGFR Mutant NSCLC Mouse Models and Murine Cell Lines: New Tools for NSCLC Research

2021 ◽  
Vol 16 (10) ◽  
pp. S917-S918
Author(s):  
E. Kleczko ◽  
A. Le ◽  
C. Hu ◽  
M. Weiser-Evans ◽  
L. Heasley ◽  
...  
MedChemComm ◽  
2018 ◽  
Vol 9 (6) ◽  
pp. 1076-1082 ◽  
Author(s):  
Mohammad Abdel-Halim ◽  
Ashraf H. Abadi ◽  
Matthias Engel

A new focused library of PKCζ inhibitors was synthesized, leading to the identification of compound2h. Owing to its improved cellular potency in human and murine cell lines, this new lead compound opens up the possibility to evaluate allosteric PKCζ inhibitors in rat or mouse models.


Cancers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 460
Author(s):  
Beatriz Medeiros-Fonseca ◽  
Antonio Cubilla ◽  
Haissa Brito ◽  
Tânia Martins ◽  
Rui Medeiros ◽  
...  

Penile cancer is an uncommon malignancy that occurs most frequently in developing countries. Two pathways for penile carcinogenesis are currently recognized: one driven by human papillomavirus (HPV) infection and another HPV-independent route, associated with chronic inflammation. Progress on the clinical management of this disease has been slow, partly due to the lack of preclinical models for translational research. However, exciting recent developments are changing this landscape, with new in vitro and in vivo models becoming available. These include mouse models for HPV+ and HPV− penile cancer and multiple cell lines representing HPV− lesions. The present review addresses these new advances, summarizing available models, comparing their characteristics and potential uses and discussing areas that require further improvement. Recent breakthroughs achieved using these models are also discussed, particularly those developments pertaining to HPV-driven cancer. Two key aspects that still require improvement are the establishment of cell lines that can represent HPV+ penile carcinomas and the development of mouse models to study metastatic disease. Overall, the growing array of in vitro and in vivo models for penile cancer provides new and useful tools for researchers in the field and is expected to accelerate pre-clinical research on this disease.


Author(s):  
Miyuki Hirabayashi ◽  
James K. Chambers ◽  
Takuya E. Kishimoto ◽  
Nguyen V. Son ◽  
Yuichi Ishikawa ◽  
...  

2003 ◽  
Vol 106 (5) ◽  
pp. 690-698 ◽  
Author(s):  
James P. Moran ◽  
Scott A. Gerber ◽  
Celeste A. Martin ◽  
John G. Frelinger ◽  
Edith M. Lord

Oncotarget ◽  
2016 ◽  
Vol 7 (34) ◽  
pp. 54137-54156 ◽  
Author(s):  
Abhilash Venugopalan ◽  
Min-Jung Lee ◽  
Gang Niu ◽  
José Medina-Echeverz ◽  
Yusuke Tomita ◽  
...  

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Xuexia Tong ◽  
Ryosuke Tanino ◽  
Rong Sun ◽  
Yukari Tsubata ◽  
Tamio Okimoto ◽  
...  

Abstract Background Protein tyrosine kinase 2 (PTK2) expression has been reported in various types of human epithelial cancers including lung cancer; however, the role of PTK2 in epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) has not been elucidated. We previously reported that pemetrexed-resistant NSCLC cell line PC-9/PEM also acquired EGFR-TKI resistance with constitutive Akt activation, but we could not find a therapeutic target. Methods Cell viability in EGFR-mutant NSCLC cell lines was measured by the WST-8 assay. Phosphorylation antibody array assay for receptor tyrosine kinases was performed in PC-9 and PC-9/PEM cell lines. We evaluated the efficacy of EGFR and PTK2 co-inhibition in EGFR-TKI-resistant NSCLC in vitro. Oral defactinib and osimertinib were administered in mice bearing subcutaneous xenografts to evaluate the efficacy of the treatment combination in vivo. Both the PTK2 phosphorylation and the treatment combination efficacy were evaluated in erlotinib-resistant EGFR-mutant NSCLC cell lines. Results PTK2 was hyperphosphorylated in PC-9/PEM. Defactinib (PTK2 inhibitor) and PD173074 (FGFR inhibitor) inhibited PTK2 phosphorylation. Combination of PTK2 inhibitor and EGFR-TKI inhibited Akt and induced apoptosis in PC-9/PEM. The combination treatment showed improved in vivo therapeutic efficacy compared to the single-agent treatments. Furthermore, erlotinib-resistant NSCLC cell lines showed PTK2 hyperphosphorylation. PTK2 inhibition in the PTK2 hyperphosphorylated erlotinib-resistant cell lines also recovered EGFR-TKI sensitivity. Conclusion PTK2 hyperphosphorylation occurs in various EGFR-TKI-resistant NSCLCs. Combination of PTK2 inhibitor and EGFR-TKI (defactinib and osimertinib) recovered EGFR-TKI sensitivity in the EGFR-TKI-resistant NSCLC. Our study result suggests that this combination therapy may be a viable option to overcome EGFR-TKI resistance in NSCLC.


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