Translating cancer research into targeted therapeutics

被引：247

作者：

de Bono, J. S. ^{[1
,2
]}

Ashworth, Alan ^{[3
]}

机构：

[1] Inst Canc Res, Sutton SM2 5NG, Surrey, England

[2] Royal Marsden NHS Fdn Trust, Sutton SM2 5PT, Surrey, England

[3] Inst Canc Res, Breakthrough Breast Canc Ctr, London SW3 6JB, England

来源：

NATURE | 2010年 / 467卷 / 7315期

关键词：

CIRCULATING TUMOR-CELLS; RESISTANT PROSTATE-CANCER; PROGRESSION-FREE SURVIVAL; CLINICAL-TRIAL; ABIRATERONE ACETATE; PHASE-I; DRUG; GENE; IMATINIB; INHIBITION;

D O I：

10.1038/nature09339

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The emphasis in cancer drug development has shifted from cytotoxic, non-specific chemotherapies to molecularly targeted, rationally designed drugs promising greater efficacy and less side effects. Nevertheless, despite some successes drug development remains painfully slow. Here, we highlight the issues involved and suggest ways in which this process can be improved and expedited. We envision an increasing shift to integrated cancer research and biomarker-driven adaptive and hypothesis testing clinical trials. The goal is the development of specific cancer medicines to treat the individual patient, with treatment selection being driven by a detailed understanding of the genetics and biology of the patient and their cancer.

引用

页码：543 / 549

页数：7

共 70 条

[61]

Therasse P, 2000, J NATL CANCER I, V92, P205, DOI 10.1093/jnci/92.3.205

[62] Recurrent fusion of TMPRSS2 and ETS transcription factor genes in prostate cancer [J].

Tomlins, SA ;

Rhodes, DR ;

Perner, S ;

Dhanasekaran, SM ;

Mehra, R ;

Sun, XW ;

Varambally, S ;

Cao, XH ;

Tchinda, J ;

Kuefer, R ;

Lee, C ;

Montie, JE ;

Shah, RB ;

Pienta, KJ ;

Rubin, MA ;

Chinnaiyan, AM .

SCIENCE, 2005, 310 (5748) :644-648

[63] Distinct classes of chromosomal rearrangements create oncogenic ETS gene fusions in prostate cancer [J].

Tomlins, Scott A. ;

Laxman, Bharathi ;

Dhanasekaran, Saravana M. ;

Helgeson, Beth E. ;

Cao, Xuhong ;

Morris, David S. ;

Menon, Anjana ;

Jing, Xiaojun ;

Cao, Qi ;

Han, Bo ;

Yu, Jindan ;

Wang, Lei ;

Montie, James E. ;

Rubin, Mark A. ;

Pienta, Kenneth J. ;

Roulston, Diane ;

Shah, Rajal B. ;

Varambally, Sooryanarayana ;

Mehra, Rohit ;

Chinnaiyan, Arul M. .

NATURE, 2007, 448 (7153) :595-U9

[64] Safety and efficacy of imatinib (ST1571) in metastatic gastrointestinal stromal tumours: a phase I study [J].

van Oosterom, AT ;

Judson, I ;

Verweij, J ;

Stroobants, S ;

di Paola, ED ;

Dimitrijevic, S ;

Martens, M ;

Webb, A ;

Sciot, R ;

Van Glabbeke, M ;

Silberman, S ;

Nielsen, OS .

LANCET, 2001, 358 (9291) :1421-1423

[65] Progression-free survival in gastrointestinal stromal tumours with high-dose imatinib: randomised trial [J].

Verweij, J ;

Casali, PG ;

Zalcberg, J ;

LeCesne, A ;

Reichardt, P ;

Blay, JY ;

Issels, R ;

van Oosterom, A ;

Hogendoorn, PCW ;

Van Glabbeke, M ;

Bertulli, R ;

Judson, I .

LANCET, 2004, 364 (9440) :1127-1134

[66] Inhibition of the Hedgehog Pathway in Advanced Basal-Cell Carcinoma. [J].

Von Hoff, Daniel D. ;

LoRusso, Patricia M. ;

Rudin, Charles M. ;

Reddy, Josina C. ;

Yauch, Robert L. ;

Tibes, Raoul ;

Weiss, Glen J. ;

Borad, Mitesh J. ;

Hann, Christine L. ;

Brahmer, Julie R. ;

Mackey, Howard M. ;

Lum, Bertram L. ;

Darbonne, Walter C. ;

Marsters, James C., Jr. ;

de Sauvage, Frederic J. ;

Low, Jennifer A. .

NEW ENGLAND JOURNAL OF MEDICINE, 2009, 361 (12) :1164-1172

[67] Cancer: Addiction to oncogenes - The Achilles heal of cancer [J].

Weinstein, IB .

SCIENCE, 2002, 297 (5578) :63-64

[68] Targeted therapeutics for cancer treatment: major progress towards personalised molecular medicine [J].

Workman, Paul ;

de Bono, Johann .

CURRENT OPINION IN PHARMACOLOGY, 2008, 8 (04) :359-362

[69] Minimally invasive pharmacokinetic and pharmacodynamic technologies in hypothesis-testing clinical trials of innovative therapies [J].

Workman, Paul ;

Aboagye, Eric O. ;

Chung, Yuen-Li ;

Griffiths, John R. ;

Hart, Rachel ;

Leach, Martin O. ;

Maxwell, Ross J. ;

McSheehy, Paul M. J. ;

Price, Pat M. ;

Zweit, Jamal .

JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE, 2006, 98 (09) :580-598

[70] Targeting the PI3K-AKT-mTOR pathway: progress, pitfalls, and promises [J].

Yap, Timothy A. ;

Garrett, Michelle D. ;

Walton, Mike I. ;

Raynaud, Florence ;

de Bono, Johann S. ;

Workman, Paul .

CURRENT OPINION IN PHARMACOLOGY, 2008, 8 (04) :393-412

← 1 2 3 4 5 6 7 →