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Journal Clin. Cancer Res.

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Next-Generation Sequencing of Cerebrospinal Fluid: How can a liquid be like a solid?

Melina E Marmarelis, Joshua M Bauml,

The APOLLO investigators showed that NGS of cerebrospinal fluid can reveal molecular alterations - how should this affect our management approach? ... Read more >>

Clin. Cancer Res. (Clinical cancer research : an official journal of the American Association for Cancer Research)
[2020, :]

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Selected Articles from This Issue.

Clin. Cancer Res. (Clinical cancer research : an official journal of the American Association for Cancer Research)
[2020, 26(19):5053]

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Delving into Early Onset Pancreatic Ductal Adenocarcinoma: How Does Age Fit In?

Erica S Tsang, James T Topham, Joanna M Karasinska, Michael Kuan-Ching Lee, Laura M Williamson, Shehara Mendis, Robert E Denroche, Gun Ho Jang, Steve E Kalloger, Richard A Moore, Andrew J Mungall, Oliver F Bathe, Patricia A Tang, Faiyaz Notta, Julie M Wilson, Janessa Laskin, Grainne M O'Kane, Jennifer J Knox, Rachel A Goodwin, Jonathan M Loree, Steven Jm Jones, Marco A Marra, Steven Gallinger, David F Schaeffer, Daniel J Renouf,

PURPOSE:With the rising incidence of early-onset pancreatic cancer (EOPC), molecular characteristics that distinguish early onset pancreatic ductal adenocarcinoma (PDAC) tumors from those arising at a later age are not well understood. EXPERIMENTAL DESIGN:We performed bioinformatic analysis of genomic and transcriptomic data generated from 269 advanced (metastatic or locally advanced) and ... Read more >>

Clin. Cancer Res. (Clinical cancer research : an official journal of the American Association for Cancer Research)
[2020, :]

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Siglec-15 as an emerging target for next-generation cancer immunotherapy.

Jingwei Sun, Qiao Lu, Miguel F Sanmanmed, Jun Wang,

Immunomodulatory agents blocking the PD-1/PD-L1 pathway have shown a new way to treat cancer. The explanation underlying the success of these agents may be the selective expression of PD-L1 with dominant immune-suppressive activities in the tumor microenvironment (TME), supporting a more favorable tumor response-to-toxicity ratio. However, despite the big success ... Read more >>

Clin. Cancer Res. (Clinical cancer research : an official journal of the American Association for Cancer Research)
[2020, :]

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Phase Ib Study of Chemoprevention with Green Tea Polyphenon E and Erlotinib in Patients with Advanced Premalignant Lesions (APL) of the Head and Neck.

Dong M Shin, Sreenivas Nannapaneni, Mihir R Patel, Qiuying Shi, Yuan Liu, Zhengjia Chen, Amy Y Chen, Mark W El-Deiry, Jonathan J Beitler, Conor E Steuer, Steven M Roser, Adam M Klein, Taofeek K Owonikoko, Suresh S Ramalingam, Fadlo R Khuri, Zhuo G Chen, Nabil F Saba,

PURPOSE:On the basis of synergistic effects between green tea polyphenon E (PPE) and EGFR-tyrosine kinase inhibitor in preclinical studies, we conducted a phase Ib study of the PPE and erlotinib combination in patients with advanced premalignant lesions (APL) of the oral cavity and larynx. PATIENTS AND METHODS:Patients were treated with ... Read more >>

Clin. Cancer Res. (Clinical cancer research : an official journal of the American Association for Cancer Research)
[2020, :]

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Intratumoral Immunotherapy: from Trial Design to Clinical Practice.

Stephane Champiat, Lambros Tselikas, Siham Farhane, Thibault Raoult, Matthieu Texier, Emilie Lanoy, Christophe Massard, Caroline Robert, Samy Ammari, Thierry De Baere, Aurelien Marabelle,

Systemic immunotherapies such as immune checkpoint blockade targeted at PD(L)1 and CTLA4 have demonstrated their ability to provide durable tumor responses and long term overall survival benefits for some patients in several solid tumor types. However, a majority of patients remain resistant to these treatments and a significant proportion of ... Read more >>

Clin. Cancer Res. (Clinical cancer research : an official journal of the American Association for Cancer Research)
[2020, :]

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Flumatinib versus Imatinib for Newly Diagnosed Chronic Phase Chronic Myeloid Leukemia: A Phase 3, Randomized, Open-label, Multi-center FESTnd Study.

Li Zhang, Li Meng, Bingcheng Liu, Yanli Zhang, Huanling Zhu, Jiuwei Cui, Aining Sun, Yu Hu, Jie Jin, Hao Jiang, Xi Zhang, Yan Li, Li Liu, Wanggang Zhang, Xiaoli Liu, Jian Gu, Jianhui Qiao, Guifang Ouyang, Xin Liu, Jianmin Luo, Ming Jiang, Xiaobao Xie, Jianyong Li, Chunting Zhao, Mei Zhang, Tonghua Yang, Jianxiang Wang,

PURPOSE:Flumatinib has been shown to be a more potent inhibitor of BCR-ABL1 tyrosine kinase than imatinib. We evaluated the efficacy and safety of flumatinib versus imatinib, for first-line treatment of chronic phase Philadelphia chromosome-positive chronic myeloid leukemia (CML-CP). EXPERIMENTAL DESIGN:In this study, 394 patients were randomized 1:1 to flumatinib 600 ... Read more >>

Clin. Cancer Res. (Clinical cancer research : an official journal of the American Association for Cancer Research)
[2020, :]

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Multiplex Immunofluorescence in Formalin-Fixed Paraffin-Embedded Tumor Tissue to Identify Single-Cell-Level PI3K Pathway Activation.

Konrad H Stopsack, Ying Huang, Svitlana Tyekucheva, Travis A Gerke, Clyde Bango, Habiba Elfandy, Michaela Bowden, Kathryn L Penney, Thomas M Roberts, Giovanni Parmigiani, Philip W Kantoff, Lorelei A Mucci, Massimo Loda,

PURPOSE:Identifying cancers with high PI3K pathway activity is critical for treatment selection and eligibility into clinical trials of PI3K inhibitors. Assessments of tumor signaling pathway activity need to consider intratumoral heterogeneity and multiple regulatory nodes. METHODS:We established a novel, mechanistically informed approach to assessing tumor signaling pathways by quantifying single-cell-level ... Read more >>

Clin. Cancer Res. (Clinical cancer research : an official journal of the American Association for Cancer Research)
[2020, :]

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Multimodal CEA-targeted image-guided colorectal cancer surgery using 111In-labeled SGM-101.

Jan Marie de Gooyer, Fortuné M K Elekonawo, Desirée L Bos, Rachel S van der Post, André Pèlegrin, Bérénice Framery, Francoise Cailler, Alexander L Vahrmeijer, Johannes H W de Wilt, Mark Rijpkema,

PURPOSE:Intraoperative image guidance may aid in clinical decision making during surgical treatment of colorectal cancer. We developed the dual-labeled CEA-targeting tracer [111In]In-DTPA-SGM-101 for pre- and intraoperative imaging of colorectal cancer. Subsequently we investigated the tracer in preclinical biodistribution and multimodal image-guided surgery studies, and assessed the clinical feasibility on patient ... Read more >>

Clin. Cancer Res. (Clinical cancer research : an official journal of the American Association for Cancer Research)
[2020, :]

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AsiDNA Is a Radiosensitizer with no Added Toxicity in Medulloblastoma Pediatric Models.

Sofia Ferreira, Chloe Foray, Alberto Gatto, Magalie Larcher, Sophie Heinrich, Mihaela Lupu, Joel Mispelter, François D Boussin, Célio Pouponnot, Marie Dutreix,

PURPOSE:Medulloblastoma is an important cause of mortality and morbidity in pediatric oncology. Here, we investigated whether the DNA repair inhibitor, AsiDNA, could help address a significant unmet clinical need in medulloblastoma care, by improving radiotherapy efficacy without increasing radiation-associated toxicity. EXPERIMENTAL DESIGN:To evaluate the brain permeability of AsiDNA upon systemic ... Read more >>

Clin. Cancer Res. (Clinical cancer research : an official journal of the American Association for Cancer Research)
[2020, :]

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Targeting isocitrate dehydrogenase mutations in cancer: emerging evidence and diverging strategies.

Matthew S Waitkus, Hai Yan,

Isocitrate dehydrogenase active-site mutations cause a neomorphic enzyme activity that results in the formation of supraphysiological concentrations of D-2-hydroxyglutarate (D-2HG). D-2HG is thought to be an oncometabolite that drives the formation of cancers in a variety of tissue types by altering the epigenetic state of progenitor cells by inhibiting enzymes ... Read more >>

Clin. Cancer Res. (Clinical cancer research : an official journal of the American Association for Cancer Research)
[2020, :]

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Editor's Note: The Pivotal Role of Integrin β1 in Metastasis of Head and Neck Squamous Cell Carcinoma.

Dongsheng Wang, Susan Müller, A R M Ruhul Amin, Donghai Huang, Ling Su, Zhongliang Hu, Mohammad Aminur Rahman, Sreenivas Nannapaneni, Lydia Koenig, Zhengjia Chen, Mourad Tighiouart, Dong M Shin, Zhuo G Chen,

Clin. Cancer Res. (Clinical cancer research : an official journal of the American Association for Cancer Research)
[2020, 26(18):5052]

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Selected Articles from This Issue.

Clin. Cancer Res. (Clinical cancer research : an official journal of the American Association for Cancer Research)
[2020, 26(17):4427]

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Correction: Paclitaxel Sensitivity of Ovarian Cancer Can be Enhanced by Knocking Down Pairs of Kinases that Regulate MAP4 Phosphorylation and Microtubule Stability.

Hailing Yang, Weiqun Mao, Cristian Rodriguez-Aguayo, Lingegowda S Mangala, Geoffrey Bartholomeusz, Lakesla R Iles, Nicholas B Jennings, Ahmed Ashour Ahmed, Anil K Sood, Gabriel Lopez-Berestein, Zhen Lu, Robert C Bast,

Clin. Cancer Res. (Clinical cancer research : an official journal of the American Association for Cancer Research)
[2020, 26(18):5050]

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Correction: Safety, Efficacy, and Biomarker Analysis of Toripalimab in Previously Treated Advanced Melanoma: Results of the POLARIS-01 Multicenter Phase II Trial.

Bixia Tang, Zhihong Chi, Yingbo Chen, Xiufeng Liu, Di Wu, Jing Chen, Xin Song, Weifeng Wang, Lihou Dong, Haifeng Song, Hai Wu, Hui Feng, Sheng Yao, Shuikui Qin, Xiaoshi Zhang, Jun Guo,

Clin. Cancer Res. (Clinical cancer research : an official journal of the American Association for Cancer Research)
[2020, 26(18):5048]

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Correction: Alterations in the Transcriptional Programs of Myeloma Cells and the Microenvironment during Extramedullary Progression Affect Proliferation and Immune Evasion.

Daeun Ryu, Seok Jin Kim, Yourae Hong, Areum Jo, Nayoung Kim, Hee-Jin Kim, Hae-Ock Lee, Kihyun Kim, Woong-Yang Park,

Clin. Cancer Res. (Clinical cancer research : an official journal of the American Association for Cancer Research)
[2020, 26(18):5049]

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Correction: Influencing the Tumor Microenvironment: A Phase II Study of Copper Depletion Using Tetrathiomolybdate in Patients with Breast Cancer at High Risk for Recurrence and in Preclinical Models of Lung Metastases.

Nancy Chan, Amy Willis, Naomi Kornhauser, Maureen M Ward, Sharrell B Lee, Eleni Nackos, Bo Ri Seo, Ellen Chuang, Tessa Cigler, Anne Moore, Diana Donovan, Marta Vallee Cobham, Veronica Fitzpatrick, Sarah Schneider, Alysia Wiener, Jessica Guillaume-Abraham, Elnaz Aljom, Richard Zelkowitz, J David Warren, Maureen E Lane, Claudia Fischbach, Vivek Mittal, Linda Vahdat,

Clin. Cancer Res. (Clinical cancer research : an official journal of the American Association for Cancer Research)
[2020, 26(18):5051]

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Selected Articles from This Issue.

Clin. Cancer Res. (Clinical cancer research : an official journal of the American Association for Cancer Research)
[2020, 26(18):4713]

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Immunomodulatory Activity of a Colony-stimulating Factor-1 Receptor Inhibitor in Patients with Advanced Refractory Breast or Prostate Cancer: A Phase I Study.

Karen A Autio, Christopher A Klebanoff, David Schaer, John Sae Wook Kauh, Susan F Slovin, Matthew Adamow, Victoria S Blinder, Manisha Brahmachary, Michelle Carlsen, Elizabeth Comen, Daniel C Danila, Thompson N Doman, Jeremy C Durack, Josef J Fox, Jill S Gluskin, David M Hoffman, Suhyun Kang, Praneet Kang, Jonathan Landa, Philomena F McAndrew, Shanu Modi, Michael J Morris, Ruslan Novosiadly, Dana E Rathkopf, Rachel Sanford, Sonya C Chapman, Courtney M Tate, Danni Yu, Phillip Wong, Heather L McArthur,

PURPOSE:Tumor-associated macrophages correlate with increased invasiveness, growth, and immunosuppression. Activation of the colony-stimulating factor-1 receptor (CSF-1R) results in proliferation, differentiation, and migration of monocytes/macrophages. This phase I study evaluated the immunologic and clinical activity, and safety profile of CSF-1R inhibition with the mAb LY3022855. PATIENTS AND METHODS:Patients with advanced refractory ... Read more >>

Clin. Cancer Res. (Clinical cancer research : an official journal of the American Association for Cancer Research)
[2020, :]

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U.S. Food and Drug Administration: Initial Experience with the Real-Time Oncology Review Program.

R Angelo de Claro, Jennifer J Gao, Tamy Kim, Paul G Kluetz, Marc R Theoret, Julia A Beaver, Richard Pazdur,

The FDA Oncology Center of Excellence (OCE) commenced the Real-Time Oncology Review (RTOR) pilot project in February 2018 to facilitate earlier submission of topline results and datasets to support an earlier start to the FDA application review. RTOR was initially begun to support supplemental drug applications to add new indications, ... Read more >>

Clin. Cancer Res. (Clinical cancer research : an official journal of the American Association for Cancer Research)
[2020, :]

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The XPO1 Inhibitor KPT-8602 Synergizes with Dexamethasone in Acute Lymphoblastic Leukemia.

Delphine Verbeke, Sofie Demeyer, Cristina Prieto, Charles E de Bock, Jolien De Bie, Olga Gielen, Kris Jacobs, Nicole Mentens, Bronte Manouk Verhoeven, Anne Uyttebroeck, Nancy Boeckx, Kim De Keersmaecker, Johan Maertens, Heidi Segers, Jan Cools,

PURPOSE:KPT-8602 (Eltanexor) is a second-generation exportin-1 (XPO1) inhibitor with potent activity against acute lymphoblastic leukemia (ALL) in preclinical models and with minimal effects on normal cells. In this study, we evaluated whether KPT-8602 would synergize with dexamethasone, vincristine, or doxorubicin, three drugs currently used for the treatment of ALL. EXPERIMENTAL ... Read more >>

Clin. Cancer Res. (Clinical cancer research : an official journal of the American Association for Cancer Research)
[2020, :]

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Spatial and temporal heterogeneity of PD-L1 expression and tumor mutational burden in gastroesophageal adenocarcinoma at baseline diagnosis and after chemotherapy.

Katherine I Zhou, Bryan F Peterson, Anthony Serritella, Joseph Thomas, Natalie Reizine, Stephanie Moya, Yi-Hung Carol Tan, Yan Wang, Daniel V T Catenacci,

PURPOSE:Intrapatient heterogeneity of programmed death ligand 1 (PD-L1) expression and tumor mutational burden (TMB) in gastroesophageal adenocarcinoma (GEA) could influence their roles as predictive biomarkers for response to immune checkpoint inhibitors (ICIs). In this retrospective analysis, we evaluated the spatiotemporal heterogeneity and prognostic relevance of PD-L1 expression and TMB in ... Read more >>

Clin. Cancer Res. (Clinical cancer research : an official journal of the American Association for Cancer Research)
[2020, :]

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Biomarkers of osimertinib response in patients with refractory, EGFR-T790M-positive non-small cell lung cancer and central nervous system metastases:the APOLLO study.

Ligang Xing, Yueyin Pan, Yuankai Shi, Yongqian Shu, Jifeng Feng, Wei Li, Lejie Cao, Lifeng Wang, Wei Gu, Yong Song, Puyuan Xing, Yutao Liu, Wen Gao, Jiuwei Cui, Nana Hu, Rutian Li, Hua Bao, Yang Shao, Jinming Yu,

INTRODUCTION:Dynamic biomarker monitoring may inform pathways for treating EGFR-T790M-positive non-small cell lung cancer (NSCLC) and central nervous system (CNS) metastases with osimertinib. This study aimed to determine the efficacy and safety of osimertinib for real-world patients with EGFR-T790M NSCLC and CNS metastases and to explore potential circulating biomarkers of therapeutic ... Read more >>

Clin. Cancer Res. (Clinical cancer research : an official journal of the American Association for Cancer Research)
[2020, :]

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Intratumoral interleukin-12 mRNA therapy promotes TH1 transformation of the tumor microenvironment.

Susannah L Hewitt, Dyane Bailey, John Zielinski, Ameya Apte, Faith Musenge, Russell Karp, Shannon Burke, Fabien Garcon, Ankita Mishra, Sushma Gurumurthy, Amanda Watkins, Kristen Arnold, James Moynihan, Eleanor Clancy-Thompson, Kathy Mulgrew, Grace Adjei, Katharina Deschler, Darren Potz, Gordon Moody, David A Leinster, Steven Novick, Michal Sulikowski, Christopher J Bagnall, Philip Martin, Jean-Martin Lapointe, Han Si, Christopher A Morehouse, Maja Sedic, Robert W Wilkinson, Ronald Herbst, Joshua P Frederick, Nadia Luheshi,

PURPOSE:Whilst immune checkpoint inhibitors such as anti-PD-L1 are rapidly becoming the standard of care in the treatment of many cancers, only a subset of treated patients have long-term responses. Interleukin 12 (IL-12) promotes anti-tumor immunity in mouse models, however systemic recombinant IL-12 had significant toxicity and limited efficacy in early ... Read more >>

Clin. Cancer Res. (Clinical cancer research : an official journal of the American Association for Cancer Research)
[2020, :]

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Immune escape after adoptive T cell therapy for malignant gliomas.

Tyler J Wildes, Kyle A Dyson, Connor P Francis, Brandon M Wummer, Changlin Yang, Oleg Yegorov, David Shin, Adam J Grippin, Bayli DiVita-Dean, Rebecca S Abraham, Christina D Pham, Ginger Moore, Carmelle Kuizon, Duane A Mitchell, Catherine T Flores,

PURPOSE:Immunotherapy is remarkably effective, yet tumor escape is common. It remains unclear how brain tumors escape immunotherapy and how to overcome this immune escape. EXPERIMENTAL DESIGN:We studied KR158B-luc glioma-bearing mice during treatment with adoptive cellular therapy (ACT) with polyclonal tumor-specific T cells. We tested the immunogenicity of primary and escaped ... Read more >>

Clin. Cancer Res. (Clinical cancer research : an official journal of the American Association for Cancer Research)
[2020, :]

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