Now showing items 1-8 of 8

    • ATMIN Is a Tumor Suppressor Gene in Lung Adenocarcinoma. 

      Foster, H; Ruiz, EJ; Moore, C; Stamp, GWH; Nye, EL; Li, N; Pan, Y; He, Y; Downward, J; Behrens, A (2019-10)
      Tumor cells proliferate rapidly and thus are frequently subjected to replication stress and the risk of incomplete duplication of the genome. Fragile sites are replicated late, making them more vulnerable to damage when ...
    • Decreased glutathione biosynthesis contributes to EGFR T790M-driven erlotinib resistance in non-small cell lung cancer. 

      Li, H; Stokes, W; Chater, E; Roy, R; de Bruin, E; Hu, Y; Liu, Z; Smit, EF; Heynen, GJ; Downward, J; Seckl, MJ; Wang, Y; Tang, H; Pardo, OE (2016-01)
      Epidermal growth factor receptor (EGFR) inhibitors such as erlotinib are novel effective agents in the treatment of EGFR-driven lung cancer, but their clinical impact is often impaired by acquired drug resistance through ...
    • Development of combination therapies to maximize the impact of KRAS-G12C inhibitors in lung cancer. 

      Molina-Arcas, M; Moore, C; Rana, S; van Maldegem, F; Mugarza, E; Romero-Clavijo, P; Herbert, E; Horswell, S; Li, L-S; Janes, MR; Hancock, DC; Downward, J (2019-09)
      KRAS represents an excellent therapeutic target in lung cancer, the most commonly mutated form of which can now be blocked using KRAS-G12C mutant-specific inhibitory trial drugs. Lung adenocarcinoma cells harboring KRAS ...
    • Disruption of the Interaction of RAS with PI 3-Kinase Induces Regression of EGFR-Mutant-Driven Lung Cancer. 

      Murillo, MM; Rana, S; Spencer-Dene, B; Nye, E; Stamp, G; Downward, J (2018-12)
      RAS family GTPases contribute directly to the regulation of type I phosphoinositide 3-kinases (PI3Ks) via RAS-binding domains in the PI3K catalytic p110 subunits. Disruption of this domain of p110α impairs RAS-mutant-onc ...
    • Efficient Genotyping of KRAS Mutant Non-Small Cell Lung Cancer Using a Multiplexed Droplet Digital PCR Approach. 

      Pender, A; Garcia-Murillas, I; Rana, S; Cutts, RJ; Kelly, G; Fenwick, K; Kozarewa, I; Gonzalez de Castro, D; Bhosle, J; O'Brien, M; Turner, NC; Popat, S; Downward, J (2015-01)
      Droplet digital PCR (ddPCR) can be used to detect low frequency mutations in oncogene-driven lung cancer. The range of KRAS point mutations observed in NSCLC necessitates a multiplex approach to efficient mutation detection ...
    • IGF1-mediated human embryonic stem cell self-renewal recapitulates the embryonic niche. 

      Wamaitha, SE; Grybel, KJ; Alanis-Lobato, G; Gerri, C; Ogushi, S; McCarthy, A; Mahadevaiah, SK; Healy, L; Lea, RA; Molina-Arcas, M; Devito, LG; Elder, K; Snell, P; Christie, L; Downward, J; Turner, JMA; Niakan, KK (2020-02-07)
      Our understanding of the signalling pathways regulating early human development is limited, despite their fundamental biological importance. Here, we mine transcriptomics datasets to investigate signalling in the human ...
    • Oncogenic RAS Signaling Promotes Tumor Immunoresistance by Stabilizing PD-L1 mRNA. 

      Coelho, MA; de Carné Trécesson, S; Rana, S; Zecchin, D; Moore, C; Molina-Arcas, M; East, P; Spencer-Dene, B; Nye, E; Barnouin, K; Snijders, AP; Lai, WS; Blackshear, PJ; Downward, J (2017-12-12)
      The immunosuppressive protein PD-L1 is upregulated in many cancers and contributes to evasion of the host immune system. The relative importance of the tumor microenvironment and cancer cell-intrinsic signaling in the ...
    • Targeting of Ras-mediated FGF signaling suppresses Pten-deficient skin tumor. 

      Mathew, G; Hannan, A; Hertzler-Schaefer, K; Wang, F; Feng, G-S; Zhong, J; Zhao, JJ; Downward, J; Zhang, X (2016-11)
      Deficiency in PTEN (phosphatase and tensin homolog deleted on chromosome 10) is the underlying cause of PTEN hamartoma tumor syndrome and a wide variety of human cancers. In skin epidermis, we have previously identified ...