Download CANCER DISCOVERY CONTENTS

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.