14.2.2018 General

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11 thoughts on “14.2.2018 General”

  1. Targeting KRAS Mutant Cancers with a Covalent G12C-Specific Inhibitor

    Matthew R. Janes, Jingchuan Zhang5, Lian-Sheng Li5, Rasmus Hansen, Ulf Peters, Xin Guo, Yuching Chen, Anjali Babbar, Sarah J. Firdaus, Levan Darjania, Jun Feng, Jeffrey H. Chen, Shuangwei Li, Shisheng Li, Yun O. Long, Carol Thach, Yuan Liu, Ata Zarieh, Tess Ely, Jeff M. Kucharski, Linda V. Kessler, Tao Wu, Ke Yu, Yi Wang, Yvonne Yao, Xiaohu Deng, Patrick P. Zarrinkar, Dirk Brehmer, Dashyant Dhanak, Matthew V. Lorenzi, Dana Hu-Lowe, Matthew P. Patricelli, Pingda Ren, Yi Liu6

    http://www.cell.com/cell/fulltext/S0092-8674(18)30041-2

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  2. Epigenetic Therapy Ties MYC Depletion to Reversing Immune Evasion and Treating Lung Cancer

    https://www.sciencedirect.com/science/article/pii/S0092867417312448?via%3Dihub

    Highlights
    •Azacitidine depletes MYC and sensitizes NSCLC to HDACi
    •Combination epigenetic treatment induces a potent anti-tumor response in vivo
    •Epigenetic treatment potentiates anti-tumor responses by modulating T cell phenotypes
    • MYC status determines tumor immunophenotype

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  3. The BET bromodomain inhibitor CPI203 overcomes resistance to ABT-199 (venetoclax) by downregulation of BFL-1/A1 in in vitro and in vivo models of MYC+/BCL2+ double hit lymphoma
    A. Esteve-Arenys, J. G. Valero, A. Chamorro-Jorganes, D. Gonzalez, V. Rodriguez, I. Dlouhy, I. Salaverria, E. Campo, D. Colomer, A. Martinez, G. Rymkiewicz, P. Pérez-Galán, A. Lopez-Guillermo & G. Roué

    https://www.nature.com/articles/s41388-017-0111-1

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  4. MSK1 regulates luminal cell differentiation and metastatic dormancy in ER+ breast cancer

    https://www.nature.com/articles/s41556-017-0021-z?WT.ec_id=NCB-201802&spMailingID=55874285&spUserID=NTU1Mzc3MjA5NwS2&spJobID=1324813989&spReportId=MTMyNDgxMzk4OQS2

    Sylwia Gawrzak, Lorenzo Rinaldi, […]Roger R. Gomis
    Nature Cell Biologyvolume 20, pages211–221 (2018)
    doi:10.1038/s41556-017-0021-z

    “Using an in vivo genome-wide short hairpin RNA screening, we identified the kinase MSK1 as an important regulator of metastatic dormancy in breast cancer. In patients with ER+ breast cancer, low MSK1 expression associates with early metastasis. We show that MSK1 downregulation impairs the differentiation of breast cancer cells, increasing their bone homing and growth capacities.” “Our results indicate that MSK1 prevents metastatic progression of ER+ breast cancer, suggesting that stratifying patients with breast cancer as high or low risk for early relapse based on MSK1 expression could improve prognosis.”
    _______________

    EXTRA: A maybe useful manuscript for those struggling to match their mouse samples with human pathologic features in breast cancer

    https://www.sciencedirect.com/science/article/pii/S1875918117301423?via%3Dihub

    Genotype-Phenotype Correlations in Breast Cancer
    Jonathan D.Marotti MD ; Stuart J.Schnitt MD
    Surgical Pathology Clinics
    Volume 11, Issue 1, March 2018, Pages 199-211

    “We review the clinical and pathologic features and underlying genetic alterations of those breast cancer subtypes with established genotype-phenotype correlations and discuss the phenotypes associated with germline mutations in genes associated with hereditary breast cancer.”

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  5. Eradication of Triple-Negative Breast Cancer Cells by Targeting Glycosylated PD-L1

    Chia-Wei Li13, Seung-Oe Lim13, Ezra M. Chung, Yong-Soo Kim, Andrew H. Park, Jun Yao, Jong-Ho Cha, Weiya Xia, Li-Chuan Chan, Taewan Kim, Shih-Shin Chang, Heng-Huan Lee, Chao-Kai Chou, Yen-Liang Liu, Hsin-Chih Yeh, Evan P. Perillo, Andrew K. Dunn, Chu-Wei Kuo, Kay-Hooi Khoo, Jennifer L. Hsu, Yun Wu, Jung-Mao Hsu, Hirohito Yamaguchi, Tzu-Hsuan Huang, Aysegul A. Sahin, Gabriel N. Hortobagyi, Stephen S. Yoo, Mien-Chie Hung1

    http://www.cell.com/cancer-cell/fulltext/S1535-6108(18)30009-6

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  6. Modulating the therapeutic response of tumours to dietary serine and glycine starvation

    Oliver D. K. Maddocks1,2, Dimitris Athineos1, Eric C. Cheung1, pearl Lee1†, Tong Zhang2, Niels J. F. van den Broek1, Gillian M. Mackay1, Christiaan F. Labuschagne1, David Gay1, Flore Kruiswijk1, Julianna Blagih1, David F. Vincent1, Kirsteen J. Campbell1, Fatih Ceteci1†, Owen J. Sansom1,2, Karen Blyth1 & Karen H. Vousden1†

    https://www.nature.com/articles/nature22056.pdf

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  7. http://www.cell.com/cell/fulltext/S0092-8674(17)31506-4

    LXR/ApoE Activation Restricts Innate Immune Suppression in Cancer
    Masoud F. Tavazoie9,’Correspondence information about the author Masoud F. TavazoieEmail the author Masoud F. Tavazoie, Ilana Pollack10, Raissa Tanqueco10, Benjamin N. Ostendorf, Bernardo S. Reis, Foster C. Gonsalves, Isabel Kurth, Celia Andreu-Agullo, Mark L. Derbyshire, Jessica Posada, Shugaku Takeda, Kimia N. Tafreshian, Eric Rowinsky, Michael Szarek, Roger J. Waltzman, Elizabeth A. Mcmillan, Connie Zhao, Monica Mita, Alain Mita, Bartosz Chmielowski, Michael A. Postow, Antoni Ribas, Daniel Mucida’Correspondence information about the author Daniel MucidaEmail the author Daniel Mucida,

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  8. Cell. 2017 Dec 14;171(7):1611-1624.e24. doi: 10.1016/j.cell.2017.10.044. Epub 2017 Nov 30.
    Single-Cell Transcriptomic Analysis of Primary and Metastatic Tumor Ecosystems in Head and Neck Cancer.
    Puram SV1, Tirosh I2, Parikh AS1, Patel AP3, Yizhak K4, Gillespie S4, Rodman C5, Luo CL6, Mroz EA7, Emerick KS8, Deschler DG8, Varvares MA8, Mylvaganam R6, Rozenblatt-Rosen O5, Rocco JW7, Faquin WC6, Lin DT9, Regev A10, Bernstein BE11.
    Author information
    Abstract

    The diverse malignant, stromal, and immune cells in tumors affect growth, metastasis, and response to therapy. We profiled transcriptomes of ∼6,000 single cells from 18 head and neck squamous cell carcinoma (HNSCC) patients, including five matched pairs of primary tumors and lymph node metastases. Stromal and immune cells had consistent expression programs across patients. Conversely, malignant cells varied within and between tumors in their expression of signatures related to cell cycle, stress, hypoxia, epithelial differentiation, and partial epithelial-to-mesenchymal transition (p-EMT). Cells expressing the p-EMT program spatially localized to the leading edge of primary tumors. By integrating single-cell transcriptomes with bulk expression profiles for hundreds of tumors, we refined HNSCC subtypes by their malignant and stromal composition and established p-EMT as an independent predictor of nodal metastasis, grade, and adverse pathologic features. Our results provide insight into the HNSCC ecosystem and define stromal interactions and a p-EMT program associated with metastasis.

    https://pdfs.semanticscholar.org/6dc2/dc471c7b927eb46fff14911c4aef2ae1afaf.pdf

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