Journal ArticleDOI
Drug penetration in solid tumours
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TLDR
The evidence that indicates that the distribution of many anticancer drugs in tumours is incomplete is summarized, and strategies that might be used either to improve drug penetration through tumour tissue or to select compounds based on their abilities to penetrate tissue are suggested, thereby increasing the therapeutic index.Abstract:
To be most effective anticancer drugs must penetrate tissue efficiently, reaching all the cancer cells that comprise the target population in a concentration sufficient to exert a therapeutic effect. Most research into the resistance of cancers to chemotherapy has concentrated on molecular mechanisms of resistance, whereas the role of limited drug distribution within tumours has been neglected. We summarize the evidence that indicates that the distribution of many anticancer drugs in tumour tissue is incomplete, and we suggest strategies that might be used either to improve drug penetration through tumour tissue or to select compounds based on their abilities to penetrate tissue, thereby increasing the therapeutic index.read more
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Inhibition of Hedgehog Signaling Enhances Delivery of Chemotherapy in a Mouse Model of Pancreatic Cancer
Kenneth P. Olive,Michael A. Jacobetz,Christian Davidson,Aarthi Gopinathan,Aarthi Gopinathan,Dominick J.O. McIntyre,Davina J. Honess,Basetti Madhu,Mae A. Goldgraben,Meredith E. Caldwell,David Allard,Kristopher K. Frese,Gina M. DeNicola,Gina M. DeNicola,Christine Feig,Chelsea Combs,Stephen P. Winter,Heather Ireland-Zecchini,Stefanie Reichelt,William J. Howat,Alex R. Chang,Mousumi Dhara,Lifu Wang,Lifu Wang,Felix Rückert,Robert Grützmann,Christian Pilarsky,Kamel Izeradjene,Sunil R. Hingorani,Pearl S. Huang,Susan E. Davies,William Plunkett,Merrill J. Egorin,Ralph H. Hruban,Nigel Whitebread,Karen McGovern,Julian Adams,Christine A. Iacobuzio-Donahue,John R. Griffiths,David A. Tuveson +39 more
TL;DR: Studying a mouse model of PDA that is refractory to the clinically used drug gemcitabine, it is found that the tumors in this model were poorly perfused and poorly vascularized, properties that are shared with human PDA.
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Bevacizumab plus Irinotecan,Fluorouracil,and Leucovorin for Metastatic Colorectal Cancer
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Targeting hypoxia in cancer therapy
William R. Wilson,Michael P. Hay +1 more
TL;DR: The two main approaches, namely bioreductive prodrugs and inhibitors of molecular targets upon which hypoxic cell survival depends are reviewed, and the particular challenges and opportunities these overlapping strategies present are addressed.
Journal ArticleDOI
Drug Resistance and the Solid Tumor Microenvironment
TL;DR: How the tumor microenvironment may be involved in the resistance of solid tumors to chemotherapy and potential strategies to improve the effectiveness of drug treatment by modifying factors relating to the tumormicroenvironment are described.
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A Tense Situation: Forcing Tumour Progression
TL;DR: The changing force that cells experience needs to be considered when trying to understand the complex nature of tumorigenesis.
References
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Journal ArticleDOI
Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer
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TL;DR: Tastuzumab combined with paclitaxel after doxorubicin and cyclophosphamide improves outcomes among women with surgically removed HER2-positive breast cancer.
Journal ArticleDOI
Hypoxia — a key regulatory factor in tumour growth
TL;DR: Cells undergo a variety of biological responses when placed in hypoxic conditions, including activation of signalling pathways that regulate proliferation, angiogenesis and death, and many elements of the hypoxia-response pathway are good candidates for therapeutic targeting.
Journal ArticleDOI
Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer
Martine Piccart-Gebhart,Marion Procter,Brian Leyland-Jones,Aron Goldhirsch,Michael Untch,Ian E. Smith,Luca Gianni,José Baselga,Richard Bell,Christian Jackisch,David Cameron,Mitch Dowsett,Carlos H. Barrios,Günther G. Steger,Chiun-Shen Huang,Martin Andersson,Moshe Inbar,Mikhail Lichinitser,István Láng,U. Nitz,Hiroji Iwata,C Thomssen,Caroline Lohrisch,Thomas M. Suter,Josef Rüschoff,Tamás Süto ý,Victoria Greatorex,Carol Ward,Eleanor McFadden,M. Stella Dolci,Richard D. Gelber +30 more
TL;DR: One year of treatment with trastuzumab after adjuvant chemotherapy significantly improves disease-free survival among women with HER2-positive breast cancer.
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