Modeling and predicting clinical efficacy for drugs targeting the tumor milieu

被引:87
作者
Singh, Mallika [1 ]
Ferrara, Napoleone [2 ]
机构
[1] Novartis Inst Biomed Res, Emeryville, CA USA
[2] Genentech Inc, San Francisco, CA 94080 USA
关键词
ENGINEERED MOUSE MODELS; MATRIX-METALLOPROTEINASE INHIBITORS; TRANSLATIONAL PROFILING APPROACH; PHASE-III TRIAL; PANCREATIC NEUROENDOCRINE; ANTIANGIOGENIC THERAPY; CANCER-IMMUNOTHERAPY; LUNG-CANCER; PRECLINICAL MODELS; PROLONGS SURVIVAL;
D O I
10.1038/nbt.2286
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Disappointing results from most late-stage clinical trials of cancer therapeutics indicate a need for improved and more-predictive animal tumor models. This insufficiency of models, combined with the advent of a class of drugs that target the tumor microenvironment rather than the tumor cell, presents new challenges for designing and interpreting preclinical efficacy studies. A comparison of the clinical efficacy of anti-angiogenic drugs with their corresponding preclinical studies over the past two decades offers many lessons that can inform and improve the design of experiments in existing mouse models. In addition, technological and logistical advances in mouse models of human cancer over the past five years have the potential to increase the clinical translatability of animal studies.
引用
收藏
页码:648 / 657
页数:10
相关论文
共 130 条
[41]   DNA Damage-Mediated Induction of a Chemoresistant Niche [J].
Gilbert, Luke A. ;
Hemann, Michael T. .
CELL, 2010, 143 (03) :355-366
[42]   Does tumour dormancy offer a therapeutic target? [J].
Goss, Paul E. ;
Chambers, Ann F. .
NATURE REVIEWS CANCER, 2010, 10 (12) :871-877
[43]   Molecular targeted therapy of lung cancer: EGFR mutations and response to EGFR inhibitors [J].
Haber, D. A. ;
Bell, D. W. ;
Sordella, R. ;
Kwak, E. L. ;
Godin-Heymann, N. ;
Sharma, S. V. ;
Lynch, T. J. ;
Settleman, J. .
Molecular Approaches to Controlling Cancer, 2005, 70 :419-426
[44]   Hallmarks of Cancer: The Next Generation [J].
Hanahan, Douglas ;
Weinberg, Robert A. .
CELL, 2011, 144 (05) :646-674
[45]   Emerging molecular biomarkers-blood-based strategies to detect and monitor cancer [J].
Hanash, Samir M. ;
Baik, Christina S. ;
Kallioniemi, Olli .
NATURE REVIEWS CLINICAL ONCOLOGY, 2011, 8 (03) :142-150
[46]   A Translational Profiling Approach for the Molecular Characterization of CNS Cell Types [J].
Heiman, Myriam ;
Schaefer, Anne ;
Gong, Shiaoching ;
Peterson, Jayms D. ;
Day, Michelle ;
Ramsey, Keri E. ;
Suarez-farinas, Mayte ;
Schwarz, Cordelia ;
Stephan, Dietrich A. ;
Surmeier, D. James ;
Greengard, Paul ;
Heintz, Nathaniel .
CELL, 2008, 135 (04) :738-748
[47]   Non-germline genetically engineered mouse models for translational cancer research [J].
Heyer, Joerg ;
Kwong, Lawrence N. ;
Lowe, Scott W. ;
Chin, Lynda .
NATURE REVIEWS CANCER, 2010, 10 (07) :470-480
[48]   Improved Survival with Ipilimumab in Patients with Metastatic Melanoma [J].
Hodi, F. Stephen ;
O'Day, Steven J. ;
McDermott, David F. ;
Weber, Robert W. ;
Sosman, Jeffrey A. ;
Haanen, John B. ;
Gonzalez, Rene ;
Robert, Caroline ;
Schadendorf, Dirk ;
Hassel, Jessica C. ;
Akerley, Wallace ;
van den Eertwegh, Alfons J. M. ;
Lutzky, Jose ;
Lorigan, Paul ;
Vaubel, Julia M. ;
Linette, Gerald P. ;
Hogg, David ;
Ottensmeier, Christian H. ;
Lebbe, Celeste ;
Peschel, Christian ;
Quirt, Ian ;
Clark, Joseph I. ;
Wolchok, Jedd D. ;
Weber, Jeffrey S. ;
Tian, Jason ;
Yellin, Michael J. ;
Nichol, Geoffrey M. ;
Hoos, Axel ;
Urba, Walter J. .
NEW ENGLAND JOURNAL OF MEDICINE, 2010, 363 (08) :711-723
[49]   Development of Ipilimumab: Contribution to a New Paradigm for Cancer Immunotherapy [J].
Hoos, Axel ;
Ibrahim, Ramy ;
Korman, Alan ;
Abdallah, Kald ;
Berman, David ;
Shahabi, Vafa ;
Chin, Kevin ;
Canetta, Renzo ;
Humphrey, Rachel .
SEMINARS IN ONCOLOGY, 2010, 37 (05) :533-546
[50]   Mechanisms of drug combinations: interaction and network perspectives [J].
Jia, Jia ;
Zhu, Feng ;
Ma, Xiaohua ;
Cao, Zhiwei W. ;
Li, Yixue X. ;
Chen, Yu Zong .
NATURE REVIEWS DRUG DISCOVERY, 2009, 8 (02) :111-128