Tag Archives: KRAS

The Improbable Targeted Therapy: KRAS as an Emerging Target in Non-Small Cell Lung Cancer (NSCLC)

The authors review promising therapeutics tested for KRAS mutant non-small cell lung cancer.
[Cell Reports Medicine]
Salgia, R., Pharaon, R., Mambetsariev, I., Nam, A., & Sattler, M. (2021). The improbable targeted therapy: KRAS as an emerging target in non-small cell lung cancer (NSCLC). Cell Reports Medicine, 2(1). https://doi.org/10.1016/j.xcrm.2020.100186 Cite
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Assessing ZNF154 Methylation in Patient Plasma as a Multicancer Marker in Liquid Biopsies from Colon, Liver, Ovarian and Pancreatic Cancer Patients

Investigators assessed the effectiveness of hypermethylation at the CpG island of ZNF154, a previously reported multi-cancer specific signature for use in a blood-based cancer detection assay.
[Scientific Reports]
Miller, B. F., Petrykowska, H. M., & Elnitski, L. (2021). Assessing ZNF154 methylation in patient plasma as a multicancer marker in liquid biopsies from colon, liver, ovarian and pancreatic cancer patients. Scientific Reports, 11(1), 221. https://doi.org/10.1038/s41598-020-80345-7 Cite
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The Amino Acid Transporter SLC7A5 Is Required for Efficient Growth of KRAS-Mutant Colorectal Cancer

The authors showed that concomitant mutation of Apc and Kras in the mouse intestinal epithelium profoundly rewires metabolism, increasing glutamine consumption.
[Nature Genetics]
Najumudeen, A. K., Ceteci, F., Fey, S. K., Hamm, G., Steven, R. T., Hall, H., Nikula, C. J., Dexter, A., Murta, T., Race, A. M., Sumpton, D., Vlahov, N., Gay, D. M., Knight, J. R. P., Jackstadt, R., Leach, J. D. G., Ridgway, R. A., Johnson, E. R., Nixon, C., … Sansom, O. J. (2021). The amino acid transporter SLC7A5 is required for efficient growth of KRAS-mutant colorectal cancer. Nature Genetics, 53(1), 16–26. https://doi.org/10.1038/s41588-020-00753-3 Cite
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Dual Inhibition of MEK and AXL Targets Tumor Cell Heterogeneity and Prevents Resistant Outgrowth Mediated by the Epithelial-to-Mesenchymal Transition in NSCLC

Researchers integrated the data from a selective drug screen in epithelial and mesenchymal Kras/p53 mutant lung tumor cells with separate datasets including reverse phase protein array and an in vivo shRNA dropout screen.
[Cancer Research]
Konen, J. M., Rodriguez, B. L., Padhye, A., Ochieng, J. K., Gibson, L., Diao, L., Fowlkes, N. W., Fradette, J. J., Peng, D. H., Cardnell, R. J., Kovacs, J. J., Wang, J., Byers, L. A., & Gibbons, D. L. (2021). Dual inhibition of MEK and AXL targets tumor cell heterogeneity and prevents resistant outgrowth mediated by the epithelial-to-mesenchymal transition in NSCLC. Cancer Research. https://doi.org/10.1158/0008-5472.CAN-20-1895 Cite
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A RAC-GEF Network Critical for Early Intestinal Tumourigenesis

Transcriptional profiling of Apc deficient intestinal tissue identified Vav3 and Tiam1 as key targets.
[Nature Communications]
Pickering, K. A., Gilroy, K., Cassidy, J. W., Fey, S. K., Najumudeen, A. K., Zeiger, L. B., Vincent, D. F., Gay, D. M., Johansson, J., Fordham, R. P., Miller, B., Clark, W., Hedley, A., Unal, E. B., Kiel, C., McGhee, E., Machesky, L. M., Nixon, C., Johnsson, A. E., … Sansom, O. J. (2021). A RAC-GEF network critical for early intestinal tumourigenesis. Nature Communications, 12(1), 56. https://doi.org/10.1038/s41467-020-20255-4 Cite
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Dysfunctional EGFR and Oxidative Stress-Induced PKD1 Signaling Drive Formation of DCLK1+ Pancreatic Stem Cells

While PanIN cells expressed oncogenic KRas and have increased activity of epidermal growth factor receptor (EGFR), the authors demonstrated that in doublecortin-like kinase 1 (DCLK1+) PanIN cells EGFR signaling was not propagated to the nucleus.
[iScience]
Martinez, A. K. F., Döppler, H. R., Bastea, L. I., Edenfield, B., Patel, T., Leitges, M., Liou, G.-Y., & Storz, P. (2021). Dysfunctional EGFR and oxidative stress-induced PKD1 signaling drive formation of DCLK1+ pancreatic stem cells. IScience, 0(0). https://doi.org/10.1016/j.isci.2020.102019 Cite
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Deciphering the Genomic and lncRNA Landscapes of Aerobic Glycolysis Identifies Potential Therapeutic Targets in Pancreatic Cancer

Integrated analysis of transcriptional profiles revealed many differentially expressed long non-coding RNAs involved in PDAC aerobic glycolysis.
[International Journal of Biological Sciences]
Zhu, L.-L., Wu, Z., Li, R.-K., Xing, X., Jiang, Y.-S., Li, J., Wang, Y.-H., Hu, L.-P., Wang, X., Qin, W.-T., Sun, Y.-W., Zhang, Z.-G., Yang, Q., & Jiang, S.-H. (2021). Deciphering the genomic and lncRNA landscapes of aerobic glycolysis identifies potential therapeutic targets in pancreatic cancer. International Journal of Biological Sciences, 17(1), 107–118. https://doi.org/10.7150/ijbs.49243 Cite
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The Novel Rexinoid MSU-42011 Is Effective for the Treatment of Preclinical Kras-Driven Lung Cancer

Investigators used MSU-42011 to treat established tumors in a clinically relevant Kras-driven mouse model of lung cancer.
[Scientific Reports]
Moerland, J. A., Zhang, D., Reich, L. A., Carapellucci, S., Lockwood, B., Leal, A. S., Krieger-Burke, T., Aleiwi, B., Ellsworth, E., & Liby, K. T. (2020). The novel rexinoid MSU-42011 is effective for the treatment of preclinical Kras-driven lung cancer. Scientific Reports, 10(1), 22244. https://doi.org/10.1038/s41598-020-79260-8 Cite
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Amgen Submits Sotorasib New Drug Application to US FDA for Advanced or Metastatic Non-Small Cell Lung Cancer with KRAS G12C Mutation

Amgen announced submission of a New Drug Application to the for sotorasib, an investigational KRASG12C inhibitor for the treatment of patients with KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer, as determined by an FDA-approved test, following at least one prior systemic therapy.
[Amgen]
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Durable Suppression of Acquired MEK Inhibitor Resistance in Cancer by Sequestering MEK from ERK and Promoting Anti-Tumor T-cell Immunity

Scientists showed that combining a type II RAFi with an allosteric MEKi durably prevents and overcomes acquired resistance among cancers with KRAS, NRAS, NF1, BRAFnon-V600 and BRAFV600 mutations.
[Cancer Discovery]
Hong, A., Piva, M., Liu, S., Hugo, W., Lomeli, S. H., Zoete, V., Randolph, C. E., Yang, Z., Wang, Y., Lee, J. J., Lo, S. J., Sun, L., Vega-Crespo, A., Garcia, A. J., Shackelford, D. B., Dubinett, S. M., Scumpia, P. O., Byrum, S. D., Tackett, A. J., … Lo, R. S. (2020). Durable Suppression of Acquired MEK Inhibitor Resistance in Cancer by Sequestering MEK from ERK and Promoting Anti-Tumor T-cell Immunity. Cancer Discovery. https://doi.org/10.1158/2159-8290.CD-20-0873 Cite
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The Hexosamine Biosynthesis Pathway Is a Targetable Liability in KRAS/LKB1 Mutant Lung Cancer

Glutamine-fructose-6-phosphate transaminase [isomerizing] 2 inhibition selectively reduced KRAS/LKB1 co-mutant tumour cell growth in culture, xenografts and genetically modified mice.
[Nature Metabolism]
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