The authors report a physiologically relevant assay enabling quantitative analysis of metastatic capacity of tumor cells following implantation into the CAM. Engraftment of as few as 103 non-small cell lung cancer and prostate cancer cell lines was sufficient for both primary tumor and metastasis formation.
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Pawlikowska, P., Tayoun, T., Oulhen, M., Faugeroux, V., Rouffiac, V., Aberlenc, A., Pommier, A. L., Honore, A., Marty, V., Bawa, O., Lacroix, L., Scoazec, J. Y., Chauchereau, A., Laplace-Builhe, C., & Farace, F. (2020). Exploitation of the chick embryo chorioallantoic membrane (CAM) as a platform for anti-metastatic drug testing. Scientific Reports, 10(1), 16876. https://doi.org/10.1038/s41598-020-73632-w Cite
The role of S6K1 in tyrosine kinase inhibitor resistance was determined in in vitro gain-and-loss of function studies and confirmed in subcutaneous and orthotopic mouse lung cancer models.
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Shen, H., Wang, G.-C., Li, X., Ge, X., Wang, M., Shi, Z.-M., Bhardwaj, V., Wang, Z.-X., Zinner, R. G., Peiper, S. C., Aplin, A. E., Jiang, B.-H., & He, J. (2020). S6K1 blockade overcomes acquired resistance to EGFR-TKIs in non-small cell lung cancer. Oncogene, 1–15. https://doi.org/10.1038/s41388-020-01497-4 Cite
Investigators showed that the presence of the tumor suppressor fragile-site associated tumor suppressor in non-small-cell lung cancer cells led to apoptosis by inducing pro-death autophagy.
[Cell Death & Disease]
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Qiu, L., Hu, L., Wang, H., Li, J., Ruan, X., Sun, B., Zhi, J., Zheng, X., Gu, L., Gao, M., Kong, P., & Zhang, J. (2020). FATS regulates polyamine biosynthesis by promoting ODC degradation in an ERβ-dependent manner in non-small-cell lung cancer. Cell Death & Disease, 11(10), 1–17. https://doi.org/10.1038/s41419-020-03052-1 Cite
The authors identified a 23-hydroxybetulinic acid derivative, namely DPBA, as a novel epidermal growth factor receptor (EGFR) small-molecule ligand. It exerted potent in vitro and in vivo anticancer activity in both EGFR wild type and mutant non-small cell lung cancer by degrading EGFR.
[Signal Transduction and Targeted Therapy]
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Yao, N., Wang, C.-R., Liu, M.-Q., Li, Y.-J., Chen, W.-M., Li, Z.-Q., Qi, Q., Lu, J.-J., Fan, C.-L., Chen, M.-F., Qi, M., Li, X.-B., Hong, J., Zhang, D.-M., & Ye, W.-C. (2020). Discovery of a novel EGFR ligand DPBA that degrades EGFR and suppresses EGFR-positive NSCLC growth. Signal Transduction and Targeted Therapy, 5(1), 1–13. https://doi.org/10.1038/s41392-020-00251-2 Cite
The authors discuss the programmed cell death-1 (PD-1)/programmed death-ligand 1 (PD-L1) blockade in combination with conventional chemotherapy, targeted therapy or immunotherapy. Meanwhile, they illustrate their underlying mechanisms in regulating the process of the cancer-immunity cycle, providing the rationale for the PD-1/PD-L1 blockade-based combination therapy.
[Pharmacology & Therapeutics]
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Bristol Myers Squibb announced that the Phase III CheckMate-816 trial met a primary endpoint of pathologic complete response in resectable non-small cell lung cancer.
[Bristol Myers Squibb]
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Amgen announced positive topline Phase II results from the CodeBreaK 100 clinical study, evaluating sotorasib in 126 patients with KRAS G12C-mutant advanced non-small cell lung cancer, who had failed a median of two prior lines of anti-cancer therapies.
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Investigators established a functional correlation between thymidylate synthase (TS), epithelial-to-mesenchymal transition (EMT), chemotherapy and metastasis and propose a network for TS mediated EMT.
[British Journal of Cancer]
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Siddiqui, M. A., Gollavilli, P. N., Ramesh, V., Parma, B., Schwab, A., Vazakidou, M. E., Natesan, R., Saatci, O., Rapa, I., Bironzo, P., Schuhwerk, H., Asangani, I. A., Sahin, O., Volante, M., & Ceppi, P. (2020). Thymidylate synthase drives the phenotypes of epithelial-to-mesenchymal transition in non-small cell lung cancer. British Journal of Cancer, 1–9. https://doi.org/10.1038/s41416-020-01095-x Cite
75% of adenocarcinomas lack targeted therapies due to scarcity of druggable drivers. The authors classified tumors based on signaling similarities and discovered subgroups within this unmet patient population.
[Clinical Cancer Research]
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Daemen, A., Cooper, J., Myrta, S., Wongchenko, M. J., Lin, E., Long, J. E., Foreman, O., Modrusan, Z., Tremayne, J. R., Cruz, C. C. de la, Merchant, M., Martin, S. E., Yan, Y., & Junttila, M. R. (2020). Transcriptional subtypes resolve tumor heterogeneity and identify vulnerabilities to MEK inhibition in lung adenocarcinoma. Clinical Cancer Research. https://doi.org/10.1158/1078-0432.CCR-20-1835 Cite
EGFR mutations are the most common oncogenic drivers in NSCLC. Significant developments have taken place which highlight the differences in tumor biology that exist between the mutant and wild-type subtypes of NSCLC.
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The generation of a tightly controlled ObLiGaRe doxycycline inducible SpCas9 (ODInCas9) transgene and its use in targeted ObLiGaRe resulted in functional integration into both human and mouse cells culminating in the generation of the ODInCas9 mouse.
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Lundin, A., Porritt, M. J., Jaiswal, H., Seeliger, F., Johansson, C., Bidar, A. W., Badertscher, L., Wimberger, S., Davies, E. J., Hardaker, E., Martins, C. P., James, E., Admyre, T., Taheri-Ghahfarokhi, A., Bradley, J., Schantz, A., Alaeimahabadi, B., Clausen, M., Xu, X., … Maresca, M. (2020). Development of an ObLiGaRe Doxycycline Inducible Cas9 system for pre-clinical cancer drug discovery. Nature Communications, 11(1), 4903. https://doi.org/10.1038/s41467-020-18548-9 Cite