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6. Combinatorial Screening of Pancreatic Adenocarcinoma Reveals Sensitivity to Drug Combinations Including Bromodomain Inhibitor Plus Neddylation Inhibitor

Author

Langdon, Casey G., primary, Platt, James T., additional, Means, Robert E., additional, Iyidogan, Pinar, additional, Mamillapalli, Ramanaiah, additional, Klein, Michael, additional, Held, Matthew A., additional, Lee, Jong Woo, additional, Koo, Ja Seok, additional, Hatzis, Christos, additional, Hochster, Howard S., additional, and Stern, David F., additional

Published
2017
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7. Mutational landscape of EGFR-, MYC-, and Kras-driven genetically engineered mouse models of lung adenocarcinoma

Author

Massachusetts Institute of Technology. Department of Biology, Koch Institute for Integrative Cancer Research at MIT, McFadden, David Glenn, Bhutkar, Arjun, Chen, Frances K., Santiago, Philip M., Jacks, Tyler E., Politi, Katerina, Song, Xiaoling, Pirun, Mono, Kim-Kiselak, Caroline, Platt, James T., Lee, Emily, Hodges, Emily, Rosebrock, Adam P., Bronson, Roderick T., Socci, Nicholas D., Hannon, Gregory J., Varmus, Harold, Massachusetts Institute of Technology. Department of Biology, Koch Institute for Integrative Cancer Research at MIT, McFadden, David Glenn, Bhutkar, Arjun, Chen, Frances K., Santiago, Philip M., Jacks, Tyler E., Politi, Katerina, Song, Xiaoling, Pirun, Mono, Kim-Kiselak, Caroline, Platt, James T., Lee, Emily, Hodges, Emily, Rosebrock, Adam P., Bronson, Roderick T., Socci, Nicholas D., Hannon, Gregory J., and Varmus, Harold

Abstract

Genetically engineered mouse models (GEMMs) of cancer are increasingly being used to assess putative driver mutations identified by large-scale sequencing of human cancer genomes. To accurately interpret experiments that introduce additional mutations, an understanding of the somatic genetic profile and evolution of GEMM tumors is necessary. Here, we performed whole-exome sequencing of tumors from three GEMMs of lung adenocarcinoma driven by mutant epidermal growth factor receptor (EGFR), mutant Kirsten rat sarcoma viral oncogene homolog (Kras), or overexpression of MYC proto-oncogene. Tumors from EGFR- and Kras-driven models exhibited, respectively, 0.02 and 0.07 nonsynonymous mutations per megabase, a dramatically lower average mutational frequency than observed in human lung adenocarcinomas. Tumors from models driven by strong cancer drivers (mutant EGFR and Kras) harbored few mutations in known cancer genes, whereas tumors driven by MYC, a weaker initiating oncogene in the murine lung, acquired recurrent clonal oncogenic Kras mutations. In addition, although EGFR- and Kras-driven models both exhibited recurrent whole-chromosome DNA copy number alterations, the specific chromosomes altered by gain or loss were different in each model. These data demonstrate that GEMM tumors exhibit relatively simple somatic genotypes compared with human cancers of a similar type, making these autochthonous model systems useful for additive engineering approaches to assess the potential of novel mutations on tumorigenesis, cancer progression, and drug sensitivity., United States. National Institutes of Health (NCI K08 160658)

Published
2017

9. SMAC mimetic Debio 1143 synergizes with taxanes, topoisomerase inhibitors and bromodomain inhibitors to impede growth of lung adenocarcinoma cells

Author

Langdon, Casey G., primary, Wiedemann, Norbert, additional, Held, Matthew A., additional, Mamillapalli, Ramanaiah, additional, Iyidogan, Pinar, additional, Theodosakis, Nicholas, additional, Platt, James T., additional, Levy, Frederic, additional, Vuagniaux, Gregoire, additional, Wang, Shaomeng, additional, Bosenberg, Marcus W., additional, and Stern, David F., additional

Published
2015
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10. Abstract 2529: Debio 1143 synergizes with taxanes, topoisomerase and bromodomain inhibitors to inhibit growth of lung adenocarcinoma

Author

Langdon, Casey G., primary, Wiedemann, Norbert, additional, Held, Matthew A., additional, Platt, James T., additional, Mamillapalli, Ramanaiah, additional, Iyidogan, Pinar, additional, Theodosakis, Nicholas, additional, Levy, Frederic, additional, Robichon, Denis, additional, Zanna, Claudio, additional, Vuagniaux, Gregoire, additional, Sorensen, Mel, additional, Wang, Shaomeng, additional, Bosenberg, Marcus W., additional, and Stern, David F., additional

Published
2015
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11. PDK1 and SGK3 Contribute to the Growth of BRAF-Mutant Melanomas and Are Potential Therapeutic Targets

Author

Scortegagna, Marzia, primary, Lau, Eric, additional, Zhang, Tongwu, additional, Feng, Yongmei, additional, Sereduk, Chris, additional, Yin, Hongwei, additional, De, Surya K., additional, Meeth, Katrina, additional, Platt, James T., additional, Langdon, Casey G., additional, Halaban, Ruth, additional, Pellecchia, Maurizio, additional, Davies, Michael A., additional, Brown, Kevin, additional, Stern, David F., additional, Bosenberg, Marcus, additional, and Ronai, Ze'ev A., additional

Published
2015
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14. Abstract A16: A drug combination screen identifies taxanes as synergistic agents with the oral IAP inhibitor Debio 1143 in non-small cell lung cancer cells.

Author

Langdon, Casey G., primary, Wiedemann, Norbert, additional, Held, Mathew A., additional, Platt, James T., additional, Lévy, Frédéric, additional, Zanna, Claudio, additional, Vuagniaux, Grégoire, additional, Sorensen, Mel, additional, Wang, Shaomeng, additional, Bosenberg, Marcus W., additional, and Stern, David F., additional

Published
2013
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