3747 Rethinking T Cells in Pancreas CancerBenjamin D. Medina and George MillerSee related article, p. 3934
3750 Overcoming the Blood–Brain Barrier with anImplantable Ultrasound DeviceAdam M. Sonabend and Roger StuppSee related article, p. 3793
CCR Drug Updates
3753 FDA Approval Summary: Pembrolizumab for theTreatment of Microsatellite Instability-High SolidTumorsLeigh Marcus, Steven J. Lemery, Patricia Keegan, andRichard Pazdur
Review
3759 PARP Inhibitors: Extending Benefit Beyond BRCA-Mutant CancersPatrick G. Pili�e, Carl M. Gay, Lauren A. Byers,Mark J. O'Connor, and Timothy A. Yap
CLINICAL TRIAL BRIEF REPORT
3772 Randomized, Double-Blind, Placebo-Controlled,Multicenter Study of Siltuximab in High-RiskSmoldering Multiple MyelomaTimothy A. Brighton, Amit Khot, Simon J. Harrison,David Ghez, BrendanM.Weiss, Andres Kirsch, Hila Magen,Mercedes Gironella, Albert Oriol, Matthew Streetly,Britte Kranenburg, Xiang Qin, Rajesh Bandekar, Peter Hu,Mary Guilfoyle, Ming Qi, Sepideh Nemat, andHartmut Goldschmidt
CLINICAL TRIALS: TARGETED THERAPY
3776 A Phase I/II Trial of Carfilzomib, PegylatedLiposomal Doxorubicin, and Dexamethasone forthe Treatment of Relapsed/Refractory MultipleMyelomaMark A. Schroeder, Mark A. Fiala, Eric Huselton,Michael H. Cardone, Savina Jaeger, Sae Rin Jean,Kathryn Shea, Armin Ghobadi, Tanya Wildes,Keith E. Stockerl-Goldstein, and Ravi Vij
3784 Phase I Study of Intermittent High-Dose LapatinibAlternating with Capecitabine for HER2-PositiveBreast Cancer Patients with Central NervousSystem MetastasesAki Morikawa, Elisa de Stanchina, Elena Pentsova,Margaret M. Kemeny, Bob T. Li, Kendrick Tang, Sujata Patil,Martin Fleisher, Catherine Van Poznak, Larry Norton, andAndrew D. Seidman
3793 Safety and Feasibility of Repeated and TransientBlood–Brain Barrier Disruption by PulsedUltrasound in Patients with RecurrentGlioblastomaAhmed Idbaih, Michael Canney, Lisa Belin,Carole Desseaux, Alexandre Vignot, Guillaume Bouchoux,Nicolas Asquier, Bruno Law-Ye, Delphine Leclercq,Anne Bissery, Yann De Rycke, Clementine Trosch,Laurent Capelle, Marc Sanson, Khe Hoang-Xuan,Caroline Dehais, Caroline Houillier,Florence Laigle-Donadey, Bertrand Mathon, Arthur Andr�e,Cyril Lafon, Jean-Yves Chapelon, Jean-Yves Delattre, andAlexandre CarpentierSee related commentary, p. 3750
3802 Alpha Particle Radium 223 Dichloride in High-riskOsteosarcoma: A Phase I Dose Escalation TrialVivek Subbiah, Pete M. Anderson, Kalevi Kairemo,KennethHess, WinstonW. Huh, Vinod Ravi, Najat C. Daw,Neeta Somaiah, Joseph A. Ludwig, Robert S. Benjamin,Sant Chawla, David S. Hong, Funda Meric-Bernstam,Gregory Ravizzini, Eugenie Kleinerman,Homer Macapinlac, and Eric Rohren
3811 Efficacy of Combined VEGFR1-3, PDGFa/b, andFGFR1-3 Blockade Using Nintedanib forEsophagogastric CancerElizabeth Won, Azfar Basunia, Walid K. Chatila,Jaclyn F. Hechtman, Joanne F. Chou, Geoffrey Y. Ku,Sree B. Chalasani, Michelle S. Boyar, Zoe Goldberg,Avni M. Desai, Yaelle Tuvy, Michael F. Berger, Laura Tang,David P. Kelsen, Mark Schattner, David H. Ilson,Marinela Capanu, David B. Solit, Nikolaus Schultz, andYelena Y. Janjigian
3818 Oxygen-enhanced MRI Is Feasible, Repeatable,and Detects Radiotherapy-induced Change inHypoxia in Xenograft Models and in Patientswith Non–small Cell Lung CancerAhmed Salem, Ross A. Little, Ayse Latif,Adam K. Featherstone, Muhammad Babur, Isabel Peset,Susan Cheung, Yvonne Watson, Victoria Tessyman,Hitesh Mistry, Garry Ashton, Caron Behan,Julian C. Matthews, Marie-Claude Asselin,Robert G. Bristow, Alan Jackson, Geoff J.M. Parker,Corinne Faivre-Finn, Kaye J. Williams, andJames P.B. O'Connor
3830 miR-31-3p Expression and Benefit from Anti-EGFR Inhibitors in Metastatic Colorectal CancerPatients Enrolled in the Prospective Phase IIPROSPECT-C TrialGayathri Anandappa, Andrea Lampis,David Cunningham, Khurum H. Khan,Kyriakos Kouvelakis, Georgios Vlachogiannis,Somaieh Hedayat, Nina Tunariu, Sheela Rao,David Watkins, Naureen Starling, Chiara Braconi,Mahnaz Darvish-Damavandi, Hazel Lote, Janet Thomas,Clare Peckitt, Ria Kalaitzaki, Nasir Khan, Nicos Fotiadis,Massimo Rugge, Ruwaida Begum, Isma Rana,Annette Bryant, Jens C. Hahne, Ian Chau, Matteo Fassan,and Nicola Valeri
3839 Association of Systemic Inflammation Index andBody Mass Index with Survival in Patients withRenal Cell Cancer Treated with NivolumabUgo De Giorgi, Giuseppe Procopio, Diana Giannarelli,Roberto Sabbatini, Alessandra Bearz, Sebastiano Buti,Umberto Basso, Manfred Mitterer, Cinzia Ortega,Paolo Bidoli, Francesco Ferraù, Lucio Crin�o,Antonio Frassoldati, Paolo Marchetti, Enrico Mini,Alessandro Scoppola, Claudio Verusio,Giuseppe Fornarini, Giacomo Cartenì, Claudia Caserta,and Cora N. Sternberg
3847 Radiomics on Gadoxetic Acid–EnhancedMagnetic Resonance Imaging for Prediction ofPostoperative Early and Late Recurrence of SingleHepatocellular CarcinomaSungwon Kim, Jaeseung Shin, Do-Young Kim,Gi Hong Choi, Myeong-Jin Kim, and Jin-Young Choi
3856 Comparative Analysis of AR Variant AR-V567esmRNA Detection Systems Reveals EminentVariability and Questions the Role as a ClinicalBiomarker in Prostate CancerChristof Bernemann, Verena Humberg, Barbara Thielen,Julie Steinestel, Xin Chen, Stefan Duensing,Andres J. Schrader, and Martin Boegemann
3865 Prediction of Distant Recurrence UsingEndoPredict Among Women with ERþ, HER2�
Node-Positive and Node-Negative Breast CancerTreated with Endocrine Therapy OnlyMartin Filipits, Peter Dubsky, Margaretha Rudas,Richard Greil, Marija Balic, Zsuzsanna Bago-Horvath,Christian F. Singer, Dominik Hlauschek, Krystal Brown,Ryan Bernhisel, Ralf Kronenwett, JohnathanM. Lancaster,Florian Fitzal, and Michael Gnant
3873 Breast Phyllodes Tumors Recruit and RepolarizeTumor-Associated Macrophages via SecretingCCL5 to Promote Malignant Progression, WhichCan Be Inhibited by CCR5 Inhibition TherapyYan Nie, Hongyan Huang, Mingyan Guo, Jiewen Chen,Wei Wu, Wende Li, Xiaoding Xu, Xiaorong Lin,Wenkui Fu, Yandan Yao, Fang Zheng, Man-Li Luo,Phei Er Saw, Herui Yao, Erwei Song, and Hai Hu
3887 Plasma miRNA Levels for Predicting TherapeuticResponse to Neoadjuvant Treatment in HER2-positive Breast Cancer: Results from theNeoALTTO TrialSerena Di Cosimo, Valentina Appierto, Sara Pizzamiglio,Paola Tiberio, Marilena V. Iorio, Florentine Hilbers,Evandro de Azambuja, Lorena de la Pe~na,Miguel Izquierdo, Jens Huober, Jos�e Baselga,Martine Piccart, Filippo G. de Braud, Giovanni Apolone,Paolo Verderio, and Maria Grazia Daidone
3896 Tumor-associated Macrophages as Prognosticand Predictive Biomarkers for PostoperativeAdjuvant Chemotherapy in Patients with Stage IIColon CancerQingyang Feng, Wenju Chang, Yihao Mao, Guodong He,Peng Zheng, Wentao Tang, Ye Wei, Li Ren, Dexiang Zhu,Meiling Ji, Yongjiu Tu, Xinyu Qin, and Jianmin Xu
3908 Molecular Characterization of Neuroendocrine-like Bladder CancerJos�e Batista da Costa, Ewan A. Gibb, Trinity J. Bivalacqua,Yang Liu, Htoo Zarni Oo, David T. Miyamoto,Mohammed Alshalalfa, Elai Davicioni, Jonathan Wright,Marc A. Dall'Era, James Douglas, Joost L. Boormans,Michiel S. Van der Heijden, Chin-Lee Wu,Bas W.G. van Rhijn, Shilpa Gupta, Petros Grivas,Kent W. Mouw, Paari Murugan, Ladan Fazli, Seong Ra,Badrinath R. Konety, Roland Seiler, Siamak Daneshmand,Omar Y. Mian, Jason A. Efstathiou, Yair Lotan, andPeter C. Black
3921 Targeting Multiple Myeloma with AMG 424, aNovel Anti-CD38/CD3 Bispecific T-cell–recruiting Antibody Optimized for Cytotoxicityand Cytokine ReleaseChristina L. Zuch de Zafra, Flordeliza Fajardo,Wendy Zhong, Matthew J. Bernett, Umesh S. Muchhal,Gregory L. Moore, Jennitte Stevens, Ryan Case,Joshua T. Pearson, Siyuan Liu, Patricia L. McElroy,Jude Canon, John R. Desjarlais, Angela Coxon,Mercedesz Balazs, and Olivier Nolan-Stevaux
3934 Mobilization of CD8þ T Cells via CXCR4Blockade Facilitates PD-1 Checkpoint Therapy inHuman Pancreatic CancerYongwoo David Seo, Xiuyun Jiang, Kevin M. Sullivan,Florencia G. Jalikis, Kimberly S. Smythe, Arezou Abbasi,Marissa Vignali, James O. Park, Sara K. Daniel,Seth M. Pollack, Teresa S. Kim, Raymond Yeung,Ian Nicholas Crispe, Robert H. Pierce, Harlan Robins, andVenu G. PillarisettySee related commentary, p. 3747
3946 Combination of Trastuzumab Emtansine andStereotactic Radiosurgery Results in High Ratesof Clinically Significant Radionecrosis andDysregulation of Aquaporin-4Priscilla K. Stumpf, Diana M. Cittelly, Tyler P. Robin,Julie A. Carlson, Kelly A. Stuhr,Maria Jose Contreras-Zarate, Steven Lai, D. RyanOrmond,ChadG. Rusthoven, Laurie E. Gaspar, Rachel Rabinovitch,Brian D. Kavanagh, Arthur Liu, Jennifer R. Diamond,Peter Kabos, and Christine M. Fisher
3954 Class 1, 2, and 3 BRAF-Mutated MetastaticColorectal Cancer: A Detailed Clinical,Pathologic, and Molecular CharacterizationMarta Schirripa, PaolaBiason, SaraLonardi,NicolettaPella,Maria Simona Pino, Federica Urbano, Carlotta Antoniotti,Chiara Cremolini, Salvatore Corallo, Filippo Pietrantonio,Fabio Gelsomino, Stefano Cascinu, Armando Orlandi,Giada Munari, Umberto Malapelle, Serena Saggio,Gabriella Fontanini, Massimo Rugge, Claudia Mescoli,Stefano Lazzi, Luca Reggiani Bonetti, Giovanni Lanza,Angelo Paolo Dei Tos, Giovanna De Maglio,Maurizio Martini, Francesca Bergamo, Vittorina Zagonel,Fotios Loupakis, and Matteo Fassan
3962 Survival FollowingChemotherapy inOvarianClearCell Carcinoma IsNotAssociatedwithPathologicalMisclassification of Tumor HistotypeMasataka Takenaka, Martin K€obel, Dale W. Garsed,Sian Fereday, Ahwan Pandey, Dariush Etemadmoghadam,Joy Hendley, Ayako Kawabata, Daito Noguchi,NozomuYanaihara,Hiroyuki Takahashi, TakakoKiyokawa,Masahiro Ikegami, Hirokuni Takano, Seiji Isonishi,Kazuhiko Ochiai, Nadia Traficante for the AustralianOvarian Cancer Study Group, Sreeja Gadipally,Timothy Semple, Dane Vassiliadis, Kausyalya Amarasinghe,Jason Li, Gisela Mir Arnau, Aikou Okamoto,Michael Friedlander, and David D. L. Bowtell
3974 Targeting CD38 Enhances the AntileukemicActivity of Ibrutinib in Chronic LymphocyticLeukemiaAlak Manna, Sonikpreet Aulakh, Prachi Jani,Salman Ahmed, Sharoon Akhtar, Marie Coignet,Michael Heckman, Zahara Meghji, Kirtipal Bhatia,Aarushi Sharma, Taimur Sher, Victoria Alegria,Fabio Malavasi, Eduardo N. Chini, Asher Chanan-Khan,Sikander Ailawadhi, and Aneel Paulus
3986 Mutational Diversity and Therapy Response inBreast Cancer: A Sequencing Analysis in theNeoadjuvant GeparSepto TrialSibylle Loibl, Denise Treue, Jan Budczies, Karsten Weber,Albrecht Stenzinger, Wolfgang D. Schmitt,Wilko Weichert, Paul Jank, Jenny Furlanetto,Frederick Klauschen, Thomas Karn, Nicole Pfarr,Gunter von Minckwitz, Markus M€obs, Christian Jackisch,Christine Sers, Andreas Schneeweiss, Peter A. Fasching,Christian Schem, Michael Hummel,Marion van Mackelenbergh, Valentina Nekljudova,Michael Untch, and Carsten Denkert
3996 Combined Inhibition of STAT3 and DNA Repairin Palbociclib-Resistant ER-Positive BreastCancerNicole M. Kettner, Smruthi Vijayaraghavan,Merih Guray Durak, Tuyen Bui, Mehrnoosh Kohansal,Min Jin Ha, Bin Liu, Xiayu Rao, Jing Wang, Min Yi,Jason P.W. Carey, Xian Chen, T. Kris Eckols,Akshara S. Raghavendra, Nuhad K. Ibrahim,Meghan Sri Karuturi, Stephanie S. Watowich,Aysegul Sahin, David J. Tweardy, Kelly K. Hunt,Debu Tripathy, and Khandan Keyomarsi
4014 Combined CD28 and 4-1BB CostimulationPotentiates Affinity-tuned Chimeric AntigenReceptor–engineered T CellsEsther Drent, Ren�ee Poels, Ruud Ruiter,NielsW.C.J. van de Donk, Sonja Zweegman, Huipin Yuan,Joost de Bruijn, Michel Sadelain, Henk M. Lokhorst,Richard W.J. Groen, Tuna Mutis, and Maria Themeli
4026 IL23-Producing Human Lung Cancer CellsPromote Tumor Growth via Conversion ofInnate Lymphoid Cell 1 (ILC1) into ILC3Jaemoon Koh, Hye Young Kim, Youngha Lee,In Kyu Park, Chang Hyun Kang, Young Tae Kim,Ji-Eun Kim, Murim Choi, Won-Woo Lee,Yoon Kyung Jeon, and Doo Hyun Chung
4038 Functional and Mechanistic Interrogation of BETBromodomain Degraders for the Treatment ofMetastatic Castration-resistant Prostate CancerSteven Kregel, Rohit Malik, Irfan A. Asangani,Kari Wilder-Romans, Thekkelnaycke Rajendiran,Lanbo Xiao, Josh N. Vo, Tanu Soni, Marcin Cieslik,Ester Fernadez-Salas, Bing Zhou, Xuhong Cao,Corey Speers, Shaomeng Wang, and Arul M. Chinnaiyan
4049 Polo-like Kinase 1 Inhibition as a TherapeuticApproach to Selectively Target BRCA1-DeficientCancer Cells by Synthetic Lethality InductionSofía Carbajosa, María Florencia Pansa, Natalia Paviolo,Andr�es M. Castellaro, Diego L. Andino, Ayel�en D. Nigra,Iris Alejandra García, Ana C. Racca,Lucía Rodriguez-Berdini, Virginia Angiolini,Laura Guantay, Florencia Villafa~nez,María Bel�en Federico, María Celeste Rodríguez-Baili,Beatriz L. Caputto, Gerard Drewes, Kevin P. Madauss,Israel Gloger, Elmer Fernandez, Germ�an A. Gil,Jos�e Luis Bocco, Vanesa Gottifredi, and Gast�on Soria
4063 Therapeutic Targeting of Non-oncogeneDependencies in High-risk NeuroblastomaChen-Tsung Huang, Chiao-Hui Hsieh, Wen-Chi Lee,Yen-Lin Liu, Tsai-Shan Yang, Wen-Ming Hsu,Yen-Jen Oyang, Hsuan-Cheng Huang, andHsueh-Fen Juan
4079 Targeting Glutamine Metabolism and RedoxState for Leukemia TherapyMark A. Gregory, Travis Nemkov, Hae J. Park,Vadym Zaberezhnyy, Sarah Gehrke, Biniam Adane,Craig T. Jordan, Kirk C. Hansen, Angelo D'Alessandro,and James DeGregori
4091 LIMS1 Promotes Pancreatic Cancer Cell Survivalunder Oxygen–Glucose Deprivation Conditionsby Enhancing HIF1A Protein TranslationChongbiao Huang, Yang Li, Zengxun Li, Yang Xu, Na Li,Yi Ge, Jie Dong, Antao Chang, Tiansuo Zhao,Xiuchao Wang, Hongwei Wang, Shengyu Yang,Keping Xie, Jihui Hao, and He Ren
4104 Clinical and Genome-wide Analysis of Cisplatin-induced Tinnitus Implicates Novel OtotoxicMechanismsOmar El Charif, BrandonMapes, Matthew R. Trendowski,Heather E. Wheeler, Claudia Wing, Paul C. Dinh Jr,Robert D. Frisina, Darren R. Feldman, Robert J. Hamilton,David J. Vaughn, Chunkit Fung,Christian Kollmannsberger, Taisei Mushiroda,Michiaki Kubo, Eric R. Gamazon, Nancy J. Cox,Robert Huddart, Shirin Ardeshir-Rouhani-Fard,Patrick Monahan, Sophie D. Fossa, Lawrence H. Einhorn,Lois B. Travis, and M. Eileen Dolan
4117 Targeted Inhibition of the Dual SpecificityPhosphatases DUSP1 and DUSP6 SuppressMPNST Growth via JNKAnnmarie Ramkissoon, Katherine E. Chaney,David Milewski, Kyle B. Williams, Rory L. Williams,Kwangmin Choi, Adam Miller, Tanya V. Kalin,Joseph G. Pressey, Sara Szabo, Mohammad Azam,David A. Largaespada, and Nancy Ratner
4128 Leukemia Inhibitory Factor Promotes Castration-resistant Prostate Cancer and NeuroendocrineDifferentiation by Activated ZBTB46Yen-Nien Liu, Shaoxi Niu, Wei-Yu Chen, Qingfu Zhang,Yulei Tao,Wei-Hao Chen, Kuo-Ching Jiang, Xufeng Chen,Huaiyin Shi, Aijun Liu, Jinhang Li, Yanjing Li,Yi-Chao Lee, Xu Zhang, and Jiaoti Huang
4141 CKLF1 Enhances Inflammation-MediatedCarcinogenesis and Prevents Doxorubicin-Induced Apoptosis via IL6/STAT3 Signaling inHCCYouyi Liu, Lijuan Liu, Yan Zhou, Ping Zhou, Qiujin Yan,Xiaobei Chen, Shuang Ding, and Fan Zhu
4155 Targeting High Mobility Group Box-1 (HMGB1)Promotes Cell Death in MyelodysplasticSyndromeAngel Y.F. Kam, Sadhna O. Piryani, Chad M. McCall,Hee Su Park, David A. Rizzieri, and Phuong L. Doan
4168 L-Type Cav 1.2 Calcium Channel-a-1C RegulatesResponse to Rituximab in Diffuse Large B-CellLymphomaJiu-Yang Zhang, Pei-Pei Zhang,Wen-Ping Zhou, Jia-Yu Yu,Zhi-Hua Yao, Jun-Feng Chu, Shu-Na Yao, Cheng Wang,Waseem Lone, Qing-Xin Xia, Jie Ma, Shu-Jun Yang,Kang-Dong Liu, Zi-Gang Dong, Yong-Jun Guo,Lynette M. Smith, Timothy W. McKeithan, Wing C. Chan,Javeed Iqbal, and Yan-Yan Liu
4179 Unexpected Activities in Regulating CiliationContribute to Off-target Effects of Targeted DrugsAnna A. Kiseleva, Vladislav A. Korobeynikov,Anna S. Nikonova, Peishan Zhang, Petr Makhov,Alexander Y. Deneka, Margret B. Einarson,Ilya G. Serebriiskii, Hanqing Liu, Jeffrey R. Peterson, andErica A. Golemis
4194 Editor's Note: The Efficacy of the Novel Dual PI3-Kinase/mTOR Inhibitor NVP-BEZ235 Comparedwith Rapamycin in Renal Cell CarcinomaDaniel C. Cho, Matthew B. Cohen, David J. Panka,Michael Collins, Musie Ghebremichael, Michael B. Atkins,Sabina Signoretti, and James W. Mier
4195 Editor's Note: Cotreatment with STI-571Enhances Tumor Necrosis Factor a-relatedApoptosis-inducing Ligand (TRAIL or Apo-2L)–induced Apoptosis of Bcr-Abl–positive HumanAcute Leukemia CellsRamadevi Nimmanapalli, Mercedes Porosnicu,Diep Nguyen, Elizabeth Worthington, Erica O'Bryan,Charles Perkins, and Kapil Bhalla
ABOUT THE COVER
Immunofluorescence staining from a case of castration-resistant prostate cancer for theexpression of leukemia inhibitory factor (LIF) with neuroendocrine (NE) markerchromogranin A (CgA). LIF expression partially colocalizes with CgA expression,demonstrating that it is produced by NE tumor cells. For details, see the article by Liu andcolleagues on page 4128 of this issue.
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