Opportunities and Challenges in the Development of Experimental Drug Combinations for Cancer

被引：99

作者：

Humphrey, Rachel W. ^{[2
]}

Brockway-Lunardi, Laura M. ^{[1
]}

Bonk, David T. ^{[3
]}

Dohoney, Kathleen M. ^{[4
]}

Doroshow, James H. ^{[5
]}

Meech, Sandra J. ^{[6
]}

Ratain, Mark J. ^{[7
,8
]}

Topalian, Suzanne L. ^{[1
]}

Pardoll, Drew M. ^{[9
]}

机构：

[1] Melanoma Res Alliance, Washington, DC 20005 USA

[2] Bristol Myers Squibb Co, Global Dev, Princeton, NJ USA

[3] Bristol Myers Squibb Co, Dept Law, Princeton, NJ USA

[4] Novartis Inst Biomed Res Inc, Oncol Translat Med, Cambridge, MA USA

[5] NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA

[6] Pfizer Inc, Pfizer Oncol, New London, CT USA

[7] Univ Chicago, Canc Res Ctr, Chicago, IL 60637 USA

[8] Univ Chicago, Dept Med, Chicago, IL 60637 USA

[9] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Sch Med, Baltimore, MD 21218 USA

来源：

JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE | 2011年 / 103卷 / 16期

关键词：

MOUSE MODEL; INHIBITION; AGENTS; IMMUNOTHERAPY; RESISTANCE; TRIALS; BRAF; MELANOMA; MEK;

D O I：

10.1093/jnci/djr246

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

It is becoming increasingly evident that cancers are dependent on a number of altered molecular pathways and can develop diverse mechanisms of resistance to therapy with single agents. Therefore, combination regimens may provide the best hope for effective therapies with durable effects. Despite preclinical data to support this notion, there are many challenges to the development of targeted combinations including scientific, economic, legal, and regulatory barriers. A discussion of these challenges and identification of models and best practices are presented with intent of aiding the research community in addressing real and perceived barriers to the development of combination therapies for cancer.

引用

页码：1222 / 1226

页数：5

共 29 条

[1]

[Anonymous], IMPR QUAL CANC CLIN

[2]

[Anonymous], 2010, Cancer Facts Figures 2010

[3]

[Anonymous], SEER CANC STAT REV 1

[4] Melanoma: A model for testing new agents in combination therapies [J].

Ascierto, Paolo A. ;

Streicher, Howard Z. ;

Sznol, Mario .

JOURNAL OF TRANSLATIONAL MEDICINE, 2010, 8

[5]

*ASS U TECHN MAN, TECHN TRANSF RES

[6] Development of Rational Drug Combinations with Investigational Targeted Agents [J].

Clark, Adam ;

Ellis, Matthew ;

Erlichman, Charles ;

Lutzker, Stuart ;

Zwiebel, James .

ONCOLOGIST, 2010, 15 (05) :496-499

[7] PERCEPTIONS OF CANCER-PATIENTS AND THEIR PHYSICIANS INVOLVED IN PHASE-I TRIALS [J].

DAUGHERTY, C ;

RATAIN, MJ ;

GROCHOWSKI, E ;

STOCKING, C ;

KODISH, E ;

MICK, R ;

SIEGLER, M .

JOURNAL OF CLINICAL ONCOLOGY, 1995, 13 (05) :1062-1072

[8] Mutations of the BRAF gene in human cancer [J].

Davies, H ;

Bignell, GR ;

Cox, C ;

Stephens, P ;

Edkins, S ;

Clegg, S ;

Teague, J ;

Woffendin, H ;

Garnett, MJ ;

Bottomley, W ;

Davis, N ;

Dicks, N ;

Ewing, R ;

Floyd, Y ;

Gray, K ;

Hall, S ;

Hawes, R ;

Hughes, J ;

Kosmidou, V ;

Menzies, A ;

Mould, C ;

Parker, A ;

Stevens, C ;

Watt, S ;

Hooper, S ;

Wilson, R ;

Jayatilake, H ;

Gusterson, BA ;

Cooper, C ;

Shipley, J ;

Hargrave, D ;

Pritchard-Jones, K ;

Maitland, N ;

Chenevix-Trench, G ;

Riggins, GJ ;

Bigner, DD ;

Palmieri, G ;

Cossu, A ;

Flanagan, A ;

Nicholson, A ;

Ho, JWC ;

Leung, SY ;

Yuen, ST ;

Weber, BL ;

Siegler, HF ;

Darrow, TL ;

Paterson, H ;

Marais, R ;

Marshall, CJ ;

Wooster, R .

NATURE, 2002, 417 (6892) :949-954

[9] Economics of new oncology drug development [J].

DiMasi, Joseph A. ;

Grabowski, Henry G. .

JOURNAL OF CLINICAL ONCOLOGY, 2007, 25 (02) :209-216

[10] Effective use of PI3K and MEK inhibitors to treat mutant Kras G12D and PIK3CA H1047R murine lung cancers [J].

Engelman, Jeffrey A. ;

Chen, Liang ;

Tan, Xiaohong ;

Crosby, Katherine ;

Guimaraes, Alexander R. ;

Upadhyay, Rabi ;

Maira, Michel ;

McNamara, Kate ;

Perera, Samanthi A. ;

Song, Youngchul ;

Chirieac, Lucian R. ;

Kaur, Ramneet ;

Lightbown, Angela ;

Simendinger, Jessica ;

Li, Timothy ;

Padera, Robert F. ;

Garcia-Echeverria, Carlos ;

Weissleder, Ralph ;

Mahmood, Umar ;

Cantley, Lewis C. ;

Wong, Kwok-Kin .

NATURE MEDICINE, 2008, 14 (12) :1351-1356

← 1 2 3 →