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CANCER DISCOVERY DECEMBER 2016 ≠ VOLUME 6 ≠ CONTENTS NUMBER 12 IN THIS Highlighted research ISSUE articles . . . . . . . . . . . . . . . . . . . . . . . .1293 NEWS Important news stories IN BRIEF affecting the community . . . . . . . . 1296 NEWS Q&A: Omid Farokhzad on IN DEPTH Nanomedicine in Cancer . . . . . .1300 RESEARCH Selected highlights of recent articles WATCH of exceptional significance from the cancer literature . . . . . . . . . . . . 1301 ONLINE For more News and Research Watch, visit Cancer Discovery online at http://cancerdiscovery.aacrjournals.org/ content/early/by/section. VIEWS In The Spotlight Oncogenic MET as an Effective Therapeutic Target in Non–Small Cell Lung Cancer Resistant to EGFR Inhibitors: The Rise of the Phoenix . . . . . . . . . . . . . . . . . . . . . . 1306 L. Trusolino See article, p. 1334 Culprit or Bystander? The Role of the Fallopian Tube in “Ovarian” High-Grade Serous Carcinoma . . . . . . . . . . . 1309 E.M. Swisher, R.L. Garcia, M.R. Kilgore, and B.M. Norquist REVIEW Targeting Cancer Metabolism: Dietary and Pharmacologic Interventions . . . . . . . . . . . . . . . . 1315 C. Vernieri, S. Casola, M. Foiani, F. Pietrantonio, F. de Braud, and V. Longo RESEARCH Acquired METD1228V Mutation and BRIEFS Resistance to MET Inhibition in Lung Cancer . . . . . . . . . . . . . . . . . . 1334 M. Bahcall, T. Sim, C.P. Paweletz, J.D. Patel, R.S. Alden, Y. Kuang, A.G. Sacher, N.D. Kim, C.A. Lydon, M.M. Awad, M.T. Jaklitsch, L.M. Sholl, P.A. Jänne, and G.R. Oxnard Précis: A patient with NSCLC responded to a type II MET inhibitor in combination with an EGFR TKI after acquisition of a METD1228V mutation conferred resistance to a type I MET inhibitor. See commentary, p. 1306 Genomics of Ovarian Cancer Progression Reveals Diverse Metastatic Trajectories Including Intraepithelial Metastasis to the Fallopian Tube . . . . . . . . . . . . . . . . . . . . . . . . . . 1342 M.A. Eckert, S. Pan, K.M. Hernandez, R.M. Loth, J. Andrade, S.L. Volchenboum, P. Faber, A. Montag, R. Lastra, M.E. Peter, S.D. Yamada, and E. Lengyel Précis: Multisite sequencing of high-grade serous ovarian cancers highlights genomic instability as an early event in disease progression and identifies a subset of serous tubal intraepithelial carcinomas as metastases rather than precursor lesions. See commentary, p. 1309 See article, p. 1342 Making the Most of Cancer Surgery with Neoadjuvant Immunotherapy . . . . . . . . . . . . . . 1312 I. Melero, P. Berraondo, M.E. Rodríguez-Ruiz, and J.L. Pérez-Gracia See article, p. 1382 ii | CANCER DISCOVERYDECEMBER 2016 www.aacrjournals.org Downloaded from cancerdiscovery.aacrjournals.org on May 12, 2017. © 2016 American Association for Cancer Research. RESEARCH Phase IB Study of Vemurafenib in ARTICLES Combination with Irinotecan and Cetuximab in Patients with Metastatic Colorectal Cancer with BRAFV600E Mutation . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1352 D.S. Hong, V.K. Morris, B. El Osta, A.V. Sorokin, F. Janku, S. Fu, M.J. Overman, S. Piha-Paul, V. Subbiah, B. Kee, A.M. Tsimberidou, D. Fogelman, J. Bellido, I. Shureiqi, H. Huang, J. Atkins, G. Tarcic, N. Sommer, R. Lanman, F. Meric-Bernstam, and S. Kopetz Précis: Vemurafenib plus irinotecan and cetuximab was generally well tolerated and achieved a 35% response rate in patients with BRAFV600E metastatic colorectal cancer, and responses correlated with BRAFV600E cfDNA levels. TGFa1-Mediated SMAD3 Enhances PD-1 Expression on Antigen-Specific T Cells in Cancer . . . . . . . . . . . . . . . . . . . . . 1366 B.V. Park, Z.T. Freeman, A. Ghasemzadeh, M.A. Chattergoon, A. Rutebemberwa, J. Steigner, M.E. Winter, T.V. Huynh, S.M. Sebald, S.-J. Lee, F. Pan, D.M. Pardoll, and A.L. Cox Précis: TGFβ1 promotes a SMAD3-dependent increase in PD-1 expression on TILs, suppressing antitumor immunity and increasing tumor growth in vivo. Improved Efficacy of Neoadjuvant Compared to Adjuvant Immunotherapy to Eradicate Metastatic Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1382 J. Liu, S.J. Blake, M.C.R. Yong, H. Harjunpää, S.F. Ngiow, K. Takeda, A. Young, J.S. O’Donnell, S. Allen, M.J. Smyth, and M.W.L. Teng Précis: Neoadjuvant immunotherapy extends survival and reduces metastatic disease more effectively than adjuvant immunotherapy in mouse models of metastatic triple-negative breast cancer. See commentary, p. 1312 Acknowledgment to Reviewers . . . . . . 1400 Correction Correction: Molecular Heterogeneity and Receptor Coamplification Drive Resistance to Targeted Therapy in MET-Amplified Esophagogastric Cancer . . . . . . . . . . . . .1402 AC icon indicates Author Choice For more information please visit http://www.aacrjournals.org ON THE COVER Bahcall and colleagues report the case of a patient with recurrent non–small cell lung cancer (NSCLC) harboring an EGFR exon 19 deletion mutation and high-level MET amplification who initially responded to a type I MET inhibitor combined with an EGFR inhibitor but acquired a METD1228V mutation that promoted resistance. Protein modeling predicted that METD1228V would not alter sensitivity to type II MET inhibitors, which bind the inactive conformation of MET. Consequently, the patient was treated with a type II MET inhibitor combined with an EGFR inhibitor and achieved an ongoing response. These results indicate that MET may be therapeutically targeted in NSCLC, and type II MET inhibitor sensitivity may be maintained even in cells resistant to type I MET inhibitors. Therefore, determining MET inhibitor resistance mechanisms may guide drug selection in patients. For details, please see the article by Bahcall and colleagues on page 1334. DECEMBER 2016CANCER DISCOVERY | iii Downloaded from cancerdiscovery.aacrjournals.org on May 12, 2017. © 2016 American Association for Cancer Research. 6 (12) Cancer Discov 2016;6:OF17-1402. Updated version E-mail alerts Reprints and Subscriptions Permissions Access the most recent version of this article at: http://cancerdiscovery.aacrjournals.org/content/6/12 Sign up to receive free email-alerts related to this article or journal. To order reprints of this article or to subscribe to the journal, contact the AACR Publications Department at [email protected]. To request permission to re-use all or part of this article, contact the AACR Publications Department at [email protected]. Downloaded from cancerdiscovery.aacrjournals.org on May 12, 2017. © 2016 American Association for Cancer Research.