Highlights of This Issue 4245

SPECIAL FEATURES

Editorial

4247 AACR Cancer Progress Report 2015: TransformingLives Through Precision MedicineKenneth C. Anderson

CCR 20th Anniversary Commentary

4248 CCR 20th Anniversary Commentary: Bevacizumabin the Treatment of Glioblastoma—The Progressand the LimitationsNataliya Mar, Annick Desjardins, and James J. Vredenburgh

CCR Translations

4251 Translating Pembrolizumab to Clinical Practice:Speak Immunology and Learn Fast!Andrea van Elsas, Hans van Eenennaam, andJohn B. HaanenSee related article, p. 4286

4254 Next Generation of Preclinical Liver CancerModelsAchimWeber, Tracy O0Connor, and Mathias HeikenwalderSee related article, p. 4440

CCR Perspectives in Drug Approval

4257 FDA Approval Summary: Olaparib Monotherapyin Patients with Deleterious Germline BRCA-Mutated Advanced Ovarian Cancer Treated withThree or More Lines of ChemotherapyGeoffrey Kim, Gwynn Ison, Amy E. McKee, Hui Zhang,Shenghui Tang, Thomas Gwise, Rajeshwari Sridhara,Eunice Lee, Abraham Tzou, Reena Philip, Haw-Jyh Chiu,Tiffany K. Ricks, Todd Palmby, Anne Marie Russell,Gaetan Ladouceur, Elimika Pfuma, Hongshan Li,Liang Zhao, Qi Liu, Rajesh Venugopal, Amna Ibrahim, andRichard Pazdur

CCR Drug Updates

4262 Blinatumomab for the Treatment of PhiladelphiaChromosome–Negative, Precursor B-cell AcuteLymphoblastic LeukemiaOfir Wolach and Richard M. Stone

Molecular Pathways

4270 Molecular Pathways: Clinical Applications andFuture Direction of Insulin-like Growth Factor-1Receptor Pathway BlockadeWade T. Iams and Christine M. Lovly

4278 Molecular Pathways: Targeting the CXCR4–CXCL12 Axis—Untapped Potential in the TumorMicroenvironmentStefania Scala

CANCER THERAPY: CLINICAL

4286 Phase I Study of Pembrolizumab (MK-3475;Anti–PD-1 Monoclonal Antibody) in Patients withAdvanced Solid TumorsAmita Patnaik, S. Peter Kang, Drew Rasco,Kyriakos P. Papadopoulos, Jeroen Elassaiss-Schaap,Muralidhar Beeram, Ronald Drengler, Cong Chen,Lon Smith, Guillermo Espino, Kevin Gergich,Liliana Delgado, Adil Daud, Jill A. Lindia,Xiaoyun Nicole Li, Robert H. Pierce, Jennifer H. Yearley,Dianna Wu, Omar Laterza, Manfred Lehnert,Robert Iannone, and Anthony W. TolcherSee related commentary, p. 4251

4294 Analysis of Inflammatory and Anemia-RelatedBiomarkers in a Randomized, Double-Blind,Placebo-Controlled Study of Siltuximab(Anti-IL6 Monoclonal Antibody) in PatientsWith Multicentric Castleman DiseaseCorey Casper, Shalini Chaturvedi, Nikhil Munshi,Raymond Wong, Ming Qi, Michael Schaffer,Rajesh Bandekar, Brett Hall, Helgi van de Velde,Jessica Vermeulen, Manjula Reddy, and Frits van Rhee

4305 Patients with Slowly Proliferative Early BreastCancer Have Low Five-Year Recurrence Rates in aPhase III Adjuvant Trial of CapecitabineJoyce O0Shaughnessy, Hartmut Koeppen, Yuanyuan Xiao,Mark R. Lackner, Devchand Paul, Christopher Stokoe,John Pippen Jr, Lea Krekow, Frankie Ann Holmes,Svetislava Vukelja, Deborah Lindquist, Scot Sedlacek,Ragene Rivera, Robert Brooks, Kristi McIntyre,Carrie Brownstein, Silke Hoersch, Joanne L. Blum, andStephen Jones

October 1, 2015 � Volume 21 � Number 19

Clinical Cancer Research

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4312 High-Dose Sirolimus and Immune-SelectivePentostatin plus CyclophosphamideConditioning Yields Stable Mixed Chimerism andInsufficient Graft-versus-Tumor ResponsesMiriam E. Mossoba, David C. Halverson,Roger Kurlander, Bazetta Blacklock Schuver,Ashley Carpenter, Brenna Hansen, Seth M. Steinberg,Syed Abbas Ali, Nishant Tageja, Frances T. Hakim,Juan Gea-Banacloche, Claude Sportes, Nancy M. Hardy,Dennis D. Hickstein, Steven Z. Pavletic, Hanh Khuu,Marianna Sabatini, David Stroncek, Bruce L. Levine,Carl H. June, Jacopo Mariotti, Olivier Rixe,Antonio Tito Fojo, Michael R. Bishop, Ronald E. Gress,and Daniel H. Fowler

4321 Phase II Study of the AKT Inhibitor MK-2206 plusErlotinib in Patients with Advanced Non–SmallCell Lung Cancer Who Previously Progressed onErlotinibPrimo N. Lara Jr, Jeff Longmate, Philip C. Mack,Karen Kelly, Mark A. Socinski, Ravi Salgia, Barbara Gitlitz,Tianhong Li, Mariana Koczywas, Karen L. Reckamp, andDavid R. Gandara

4327 Phase Ia Study of FoxP3þ CD4 Treg Depletion byInfusion of a Humanized Anti-CCR4 Antibody,KW-0761, in Cancer PatientsKoji Kurose, Yoshihiro Ohue, Hisashi Wada,Shinsuke Iida, Takashi Ishida, Takashi Kojima,Toshihiko Doi, Susumu Suzuki, Midori Isobe,Takeru Funakoshi, Kazuhiro Kakimi,Hiroyoshi Nishikawa, Heiichiro Udono, Mikio Oka,Ryuzo Ueda, and Eiichi Nakayama

PERSONALIZED MEDICINE AND IMAGING

4337 Pharmacoethnicity in Paclitaxel-Induced SensoryPeripheral NeuropathyMasaaki Komatsu, Heather E. Wheeler, Suyoun Chung,Siew-Kee Low, Claudia Wing, Shannon M. Delaney,Lidija K. Gorsic, Atsushi Takahashi, Michiaki Kubo,Deanna L. Kroetz, Wei Zhang, Yusuke Nakamura, andM. Eileen Dolan

4347 Rectal Optical Markers for In Vivo RiskStratification of Premalignant Colorectal LesionsAndrew J. Radosevich, Nikhil N. Mutyal, Adam Eshein,The-Quyen Nguyen, Bradley Gould, Jeremy D. Rogers,Michael J. Goldberg, Laura K. Bianchi, Eugene F. Yen,Vani Konda, Douglas K. Rex, Jacques Van Dam,Vadim Backman, and Hemant K. Roy

4356 FGFR1 Expression Levels Predict BGJ398Sensitivity of FGFR1-Dependent Head and NeckSquamous Cell CancersFriederike G€oke, Alina Franzen, Trista K. Hinz,Lindsay A. Marek, Petros Yoon, Rakesh Sharma,Maike Bode, Anne von Maessenhausen,Brigitte Lankat-Buttgereit, Antonia G€oke, Carsten Golletz,Robert Kirsten, Diana Boehm, Wenzel Vogel,Emily K. Kleczko, Justin R. Eagles, Fred R. Hirsch,Tobias Van Bremen, Friedrich Bootz, Andreas Schroeck,Jihye Kim, Aik-Choon Tan, Antonio Jimeno,Lynn E. Heasley, and Sven Perner

4365 Association of PIK3CA Mutation Status beforeand after Neoadjuvant Chemotherapy withResponse to Chemotherapy in Women withBreast CancerHua Yuan, Jiuan Chen, Yiqiang Liu, Tao Ouyang,Jinfeng Li, Tianfeng Wang, Zhaoqing Fan, Tie Fan,Benyao Lin, and Yuntao Xie

4373 Quantification of Nonenhancing Tumor Burdenin Gliomas Using Effective T2 Maps Derived fromDual-Echo Turbo Spin-Echo MRIBenjamin M. Ellingson, Albert Lai, Huytram N. Nguyen,Phioanh L. Nghiemphu, Whitney B. Pope, andTimothy F. Cloughesy

4384 PET/CT Improves the Definition of CompleteResponse and Allows to Detect OtherwiseUnidentifiable Skeletal Progression in MultipleMyelomaElena Zamagni, Cristina Nanni, Katia Mancuso,Paola Tacchetti, Annalisa Pezzi, Lucia Pantani,Beatrice Zannetti, Ilaria Rambaldi, Annamaria Brioli,Serena Rocchi, Carolina Terragna, Marina Martello,Giulia Marzocchi, Enrica Borsi, Ilaria Rizzello,Stefano Fanti, and Michele Cavo

CANCER THERAPY: PRECLINICAL

4391 Ofatumumab Exhibits Enhanced In Vitro andIn Vivo Activity Compared to Rituximab inPreclinical Models of Mantle Cell LymphomaMatthew J. Barth, Cory Mavis, Myron S. Czuczman, andFrancisco J. Hernandez-Ilizaliturri

4398 b-Cryptoxanthin Synergistically Enhances theAntitumoral Activity of Oxaliplatin throughDNP73 Negative Regulation in Colon CancerCoral San Mill�an, Beatriz Soldevilla, Paloma Martín,Beatriz Gil-Calder�on, Marta Compte,Bel�en P�erez-Sacrist�an, Encarnaci�on Donoso,Cristina Pe~na, Jesús Romero,Fernando Granado-Lorencio, F�elix Bonilla, andGemma Domínguez

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4410 Tumor-Targeted Synergistic Blockade of MAPKand PI3K from a Layer-by-Layer NanoparticleErik C. Dreaden, Yi Wen Kong, Stephen W. Morton,Santiago Correa, Ki Young Choi, Kevin E. Shopsowitz,Kasper Renggli, Ronny Drapkin, Michael B. Yaffe, andPaula T. Hammond

4420 Hepatitis B Virus X Protein (HBx) Is Responsiblefor Resistance to Targeted Therapies inHepatocellular Carcinoma: Ex Vivo CultureEvidencePinbo Huang, Baoxiong Zhuang, Heyun Zhang,Haiyan Yan, Zhiyu Xiao, Wenbin Li, Jianlong Zhang,Qibin Tang, Kaishun Hu, H. Phillip Koeffler, Jie Wang,and Dong Yin

4431 Targeting of HPV-16þ Epithelial Cancer Cells byTCR Gene Engineered T Cells Directed against E6Lindsey M. Draper, Mei Li M. Kwong, Alena Gros,Sanja Stevanovi�c, Eric Tran, Sid Kerkar, Mark Raffeld,Steven A. Rosenberg, and Christian S. Hinrichs

4440 Model Matters: Differences in Orthotopic RatHepatocellular Carcinoma Physiology DetermineTherapy Response to SorafenibClaudia Groß, Katja Steiger, Sufyan Sayyed, Irina Heid,Annette Feuchtinger, Axel Walch, Julia Heß,Kristian Unger, Horst Zitzelsberger, Marcus Settles,Anna Melissa Schlitter, Juliane Dworniczak,Jennifer Altomonte, Oliver Ebert, Markus Schwaiger,Ernst Rummeny, Andreas Steing€otter, Irene Esposito, andRickmer BrarenSee related commentary, p. 4254

BIOLOGY OF HUMAN TUMORS

4451 Spatiotemporal Heterogeneity Characterizes theGenetic Landscape of Pheochromocytoma andDefines Early Events in TumorigenesisJoakim Crona, Samuel Backman, Rajani Maharjan,Markus Mayrhofer, Peter Sta

�lberg, Anders Isaksson,

Per Hellman, and Peyman Bj€orklund

4461 Subclonal Genomic Architectures of Primary andMetastatic Colorectal Cancer Based onIntratumoral Genetic HeterogeneityTae-Min Kim, Seung-Hyun Jung, Chang Hyeok An,Sung Hak Lee, In-Pyo Baek, Min Sung Kim,Sung-Won Park, Je-Keun Rhee, Sug-Hyung Lee, andYeun-Jun Chung

4473 New DNA Methylation Markers for PancreaticCancer: Discovery, Tissue Validation, and PilotTesting in Pancreatic JuiceJohn B. Kisiel, Massimo Raimondo, William R. Taylor,Tracy C. Yab, Douglas W. Mahoney, Zhifu Sun,Sumit Middha, Saurabh Baheti, Hongzhi Zou,Thomas C. Smyrk, Lisa A. Boardman, Gloria M. Petersen,and David A. Ahlquist

4482 Tissue Transglutaminase Mediated Tumor–Stroma Interaction Promotes Pancreatic CancerProgressionJiyoon Lee, Salvatore Condello, Bakhtiyor Yakubov,Robert Emerson, Andrea Caperell-Grant,Kiyotaka Hitomi, Jingwu Xie, and Daniela Matei

LETTER TO THE EDITOR

4494 Ancient Retrovirus Targeted by EngineeredT Cells in Melanoma—LetterJohn M. Grange and Bernd Krone

CORRECTIONS

4495 Correction: Pancreatic Cancer-Derived ExosomesCauses Paraneoplastic b-cell Dysfunction

4496 Correction: The Prostate Cancer SusceptibilityVariant rs2735839 Near KLK3 Gene Is Associatedwith Aggressive Prostate Cancer and Can StratifyGleason Score 7 Patients

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ABOUT THE COVER

The cover depicts a tumor-targeting nanoscale drug formulation based on layer-by-layer (LbL) self-assembly, here penetrating deeply through a dense tumor spheroid as imaged by confocal fluorescencemicroscopy. The authors show that these nanotechnologies can further enhance drug synergy associatedwith simultaneous blockade of MAPK and PI3K pathway signaling in tumor cells, eliciting diseasestabilization in vivo in the absence of dose-limiting toxic effects observed from the free drug combination.For details, see the article by Dreaden and colleagues on page 4410 of this issue.

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