In primary NSCLC cells and established cell lines ASP4132 potently inhibited cell growth, proliferation and cell cycle progression as well as cell migration and invasion.
[Cell Death & Disease]
The authors report that C3G downregulation promoted the acquisition of a more mesenchymal phenotype that enhanced the migratory and invasive capacity of glioblastoma cells.
[Cell Death & Disease]
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Manzano, S., Gutierrez-Uzquiza, A., Bragado, P., Sequera, C., Herranz, Ó., Rodrigo-Faus, M., Jauregui, P., Morgner, S., Rubio, I., Guerrero, C., & Porras, A. (2021). C3G downregulation induces the acquisition of a mesenchymal phenotype that enhances aggressiveness of glioblastoma cells. Cell Death & Disease, 12(4), 1–17. https://doi.org/10.1038/s41419-021-03631-w Cite
Roche announced that the European Medicines Agency’s Committee for Medicinal Products for Human Use has recommended the approval of Tecentriq® as a first-line treatment for adults with metastatic non-small cell lung cancer whose tumors have high PD-L1 expression, with no epidermal growth factor receptor or anaplastic lymphoma kinase genomic tumor aberrations.
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To elucidate the interplay between epidermal growth factor signaling and extracellular-regulated kinase activation in tumors, scientists used patient-derived organoids from KRAS and BRAF mutant colorectal cancer.
[Nature Cell Biology]
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Ponsioen, B., Post, J. B., Buissant des Amorie, J. R., Laskaris, D., van Ineveld, R. L., Kersten, S., Bertotti, A., Sassi, F., Sipieter, F., Cappe, B., Mertens, S., Verlaan-Klink, I., Boj, S. F., Vries, R. G. J., Rehmann, H., Vandenabeele, P., Riquet, F. B., Trusolino, L., Bos, J. L., & Snippert, H. J. G. (2021). Quantifying single-cell ERK dynamics in colorectal cancer organoids reveals EGFR as an amplifier of oncogenic MAPK pathway signalling. Nature Cell Biology, 1–14. https://doi.org/10.1038/s41556-021-00654-5 Cite
Scientists performed the basal-like breast cancers (BLBC) tissue microarray–based immunohistochemical analysis and showed that Faciogenital Dysplasia 5 (FGD5) abundance is associated with poor prognosis in BLBCs. FGD5 deletion decreased the proliferation, invasion, and tumorsphere formation capacity of BLBC cells.
[Science Translational Medicine]
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Li, K., Zhang, T., Zhao, C., Wang, F., Cui, B., Yang, Z., Lv, X., Yeerjiang, Z., Yuan, Y., Yu, J., Wang, Z., Zhang, X., Yu, J., Liu, S., Shang, S., Huang, B., Hua, F., & Hu, Z. (2021). Faciogenital Dysplasia 5 supports cancer stem cell traits in basal-like breast cancer by enhancing EGFR stability. Science Translational Medicine, 13(586). https://doi.org/10.1126/scitranslmed.abb2914 Cite
Using a CRISPR activation screening, scientists identified genes involved in BRAF inhibitor (BRAFi) resistance in cutaneous melanoma. Their upregulation promoted tumour growth of therapy‐naïve melanoma cells and BRAFi‐resistance.
[EMBO Molecular Medicine]
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CRISPR screens identify tumor‐promoting genes conferring melanoma cell plasticity and resistance | EMBO Molecular Medicine. (n.d.). Retrieved March 22, 2021, from https://www.embopress.org/doi/full/10.15252/emmm.202013466 Cite
Musashi-2 (MSI2) control of epidermal growth factor receptor (EGFR) expression and activity in an NSCLC cell line panel was studied using RT-PCR, Western blots, and RNA immunoprecipitation. Functional consequences of MSI2 depletion were explored for cell growth and response to EGFR-targeting drugs, in vitro and in vivo.
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Makhov, P., Bychkov, I., Faezov, B., Deneka, A., Kudinov, A., Nicolas, E., Brebion, R., Avril, E., Cai, K. Q., Kharin, L. V., Voloshin, M., Frantsiyants, E., Karnaukhov, N., Kit, O. I., Topchu, I., Fazliyeva, R., Nikonova, A. S., Serebriiskii, I. G., Borghaei, H., … Boumber, Y. (2021). Musashi-2 (MSI2) regulates epidermal growth factor receptor (EGFR) expression and response to EGFR inhibitors in EGFR-mutated non-small cell lung cancer (NSCLC). Oncogenesis, 10(3), 1–14. https://doi.org/10.1038/s41389-021-00317-y Cite
In this review, scientists discuss some uncommon alterations in NSCLC such as ROS1, BRAF, RET, HER2, NTRK, MET and other targets that are in an early evaluation phase.
[Critical Reviews in Oncology/Hematology]
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De Toma, A., Lo Russo, G., Signorelli, D., Pagani, F., Randon, G., Galli, G., Prelaj, A., Ferrara, R., Proto, C., Ganzinelli, M., Zilembo, N., de Braud, F., & Garassino, M. C. (2021). Uncommon targets in non-small cell lung cancer: Everyone wants a slice of cake. Critical Reviews in Oncology/Hematology, 160, 103299. https://doi.org/10.1016/j.critrevonc.2021.103299 Cite
Investigators report that EGFRvIII demonstrated a reliance on PDGFRA co-stimulatory signaling during the tumorigenic process in a genetically engineered autochthonous glioblastoma model.
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The authors report an activation mechanism of EGFR signaling in glioblastoma (GBM) by a secretory E-cadherin protein variant (C-E-Cad) encoded by a circular E-cadherin RNA through multiple-round open reading frame translation. C-E-Cad variant was overexpressed in GBM and promoted glioma stem cell tumorigenicity.
[Nature Cell Biology]
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Gao, X., Xia, X., Li, F., Zhang, M., Zhou, H., Wu, X., Zhong, J., Zhao, Z., Zhao, K., Liu, D., Xiao, F., Xu, Q., Jiang, T., Li, B., Cheng, S.-Y., & Zhang, N. (2021). Circular RNA-encoded oncogenic E-cadherin variant promotes glioblastoma tumorigenicity through activation of EGFR–STAT3 signalling. Nature Cell Biology, 1–14. https://doi.org/10.1038/s41556-021-00639-4 Cite
The authors found that EGFR expression begins to sharply increase after gestational week 20, which corresponds to the beginning stages of human gliogenesis.
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Fu, Y., Yang, M., Yu, H., Wang, Y., Wu, X., Yong, J., Mao, Y., Cui, Y., Fan, X., Wen, L., Qiao, J., & Tang, F. (2021). Heterogeneity of glial progenitor cells during the neurogenesis-to-gliogenesis switch in the developing human cerebral cortex. Cell Reports, 34(9). https://doi.org/10.1016/j.celrep.2021.108788 Cite