Lung Cancer Program
The DF/HCC Lung Cancer Program conducts innovative research on the causes and pathogenesis of lung cancer, focusing on discoveries that will ultimately lead to improvements in prevention, diagnosis, prognosis, and therapy. The Program has continued to make strides in areas of lung cancer susceptibility using molecular epidemiology. Investigators in the Program are carrying out systematic genomic characterization of lung cancers to identify therapeutic targets, employing structural biology and medicinal chemistry to effectively target the genomic changes, and defining mechanisms of resistance to develop therapeutic strategies to overcome the acquired resistance.
Program members (approximately 60 researchers in total) are based in multiple institutions, departments, and disciplines and have expertise in smoking cessation, genetic susceptibility to tobacco smoke, the genetic changes in lung cancer, mRNA expression patterns, and novel therapeutic approaches, including pre-clinical modeling, conducting clinical trials of novel therapies, and characterization of acquired resistance.
- Fillmore CM, Xu C, Desai PT, Berry JM, Rowbotham SP, Lin YJ, Zhang H, Marquez VE, Hammerman PS, Wong KK, Kim CF. EZH2 inhibition sensitizes BRG1 and EGFR mutant lung tumours to TopoII inhibitors. Nature 2015; 520:239-42. PubMed
- Wilson FH, Johannessen CM, Piccioni F, Tamayo P, Kim JW, Van Allen EM, Corsello SM, Capelletti M, Calles A, Butaney M, Sharifnia T, Gabriel SB, Mesirov JP, Hahn WC, Engelman JA, Meyerson M, Root DE, Jänne PA, Garraway LA. A Functional Landscape of Resistance to ALK Inhibition in Lung Cancer. Cancer Cell 2015; 27:397-408. PubMed
- Crystal AS, Shaw AT, Sequist LV, Friboulet L, Niederst MJ, Lockerman EL, Frias RL, Gainor JF, Amzallag A, Greninger P, Lee D, Kalsy A, Gomez-Caraballo M, Elamine L, Howe E, Hur W, Lifshits E, Robinson HE, Katayama R, Faber AC, Awad MM, Ramaswamy S, Mino-Kenudson M, Iafrate AJ, Benes CH, Engelman JA. Patient-derived models of acquired resistance can identify effective drug combinations for cancer. Science 2014; 346:1480-6. PubMed
- Christensen CL, Kwiatkowski N, Abraham BJ, Carretero J, Al-Shahrour F, Zhang T, Chipumuro E, Herter-Sprie GS, Akbay EA, Altabef A, Zhang J, Shimamura T, Capelletti M, Reibel JB, Cavanaugh JD, Gao P, Liu Y, Michaelsen SR, Poulsen HS, Aref AR, Barbie DA, Bradner JE, George RE, Gray NS, Young RA, Wong KK. Targeting transcriptional addictions in small cell lung cancer with a covalent CDK7 inhibitor. Cancer Cell 2014; 26:909-22. PubMed
- Shaw AT, Ou SH, Bang YJ, Camidge DR, Solomon BJ, Salgia R, Riely GJ, Varella-Garcia M, Shapiro GI, Costa DB, Doebele RC, Le LP, Zheng Z, Tan W, Stephenson P, Shreeve SM, Tye LM, Christensen JG, Wilner KD, Clark JW, Iafrate AJ. Crizotinib in ROS1-Rearranged Non-Small-Cell Lung Cancer. N Engl J Med 2014. PubMed
- Zhao R, Fallon TR, Saladi SV, Pardo-Saganta A, Villoria J, Mou H, Vinarsky V, Gonzalez-Celeiro M, Nunna N, Hariri LP, Camargo F, Ellisen LW, Rajagopal J. Yap tunes airway epithelial size and architecture by regulating the identity, maintenance, and self-renewal of stem cells. Dev Cell 2014; 30:151-65. PubMed
- Xu C, Fillmore CM, Koyama S, Wu H, Zhao Y, Chen Z, Herter-Sprie GS, Akbay EA, Tchaicha JH, Altabef A, Reibel JB, Walton Z, Ji H, Watanabe H, Jänne PA, Castrillon DH, Rustgi AK, Bass AJ, Freeman GJ, Padera RF, Dranoff G, Hammerman PS, Kim CF, Wong KK. Loss of Lkb1 and Pten leads to lung squamous cell carcinoma with elevated PD-L1 expression. Cancer Cell 2014; 25:590-604. PubMed
- Shaw AT, Kim DW, Mehra R, Tan DS, Felip E, Chow LQ, Camidge DR, Vansteenkiste J, Sharma S, De Pas T, Riely GJ, Solomon BJ, Wolf J, Thomas M, Schuler M, Liu G, Santoro A, Lau YY, Goldwasser M, Boral AL, Engelman JA. Ceritinib in ALK-rearranged non-small-cell lung cancer. N Engl J Med 2014; 370:1189-97. PubMed
- Yasuda H, Park E, Yun CH, Sng NJ, Lucena-Araujo AR, Yeo WL, Huberman MS, Cohen DW, Nakayama S, Ishioka K, Yamaguchi N, Hanna M, Oxnard GR, Lathan CS, Moran T, Sequist LV, Chaft JE, Riely GJ, Arcila ME, Soo RA, Meyerson M, Eck MJ, Kobayashi SS, Costa DB. Structural, biochemical, and clinical characterization of epidermal growth factor receptor (EGFR) exon 20 insertion mutations in lung cancer. Sci Transl Med 2013; 5:216ra177. PubMed
- Akbay EA, Koyama S, Carretero J, Altabef A, Tchaicha JH, Christensen CL, Mikse OR, Cherniack AD, Beauchamp EM, Pugh TJ, Wilkerson MD, Fecci PE, Butaney M, Reibel JB, Soucheray M, Cohoon TJ, Janne PA, Meyerson M, Hayes DN, Shapiro GI, Shimamura T, Sholl LM, Rodig SJ, Freeman GJ, Hammerman PS, Dranoff G, Wong KK. Activation of the PD-1 pathway contributes to immune escape in EGFR-driven lung tumors. 2013. PubMed
- Tata PR, Mou H, Pardo-Saganta A, Zhao R, Prabhu M, Law BM, Vinarsky V, Cho JL, Breton S, Sahay A, Medoff BD, Rajagopal J. Dedifferentiation of committed epithelial cells into stem cells in vivo. Nature 2013; 503:218-23. PubMed