Skip to main content

We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.

Close cookie message
Cancel
×
×
Home
  • Home
Chapter
  • Print publication year: 2011
  • Online publication date: April 2011

7 - TRANSLATIONAL MEDICINE IN ONCOLOGY

Export citation
Summary

Translational medicine (TM) has many definitions in many settings, but a common theme is to take biomedical research from “bench-to- bedside” using various classes of biomarkers to speed drug-development decisions. For a variety of reasons that will be discussed in this chapter, TM and biomarkers have arguably had their greatest impact in the area of oncology. Cancer drug development differs in many ways from drug development in other therapeutic areas, and the use of biomarkers as surrogates for clinical benefit has had a long history in oncology. In this chapter, we will explore the use of various classes of biomarkers in oncologic drug development and establish some general principles and points to consider when using translational approaches to cancer therapeutics.

A biomarker is defined as “a characteristic that is measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacological responses to a therapeutic intervention.” For the purposes of this chapter, three major classes of biomarkers are defined based on how they are used in the development of cancer drugs: pharmacodynamic (PD) biomarkers, outcome biomarkers, and patient selection biomarkers.

Pharmacodynamic Biomarkers

PD biomarkers, sometimes called “target” or “mechanism” biomarkers, are largely concerned with direct biochemical or physiologic effects of drugs on their intended targets (e.g., enzyme inhibition, receptor antagonism) independent of any relationship to potential clinical benefit.

Recommend this book

Email your librarian or administrator to recommend adding this book to your organisation's collection.

Translational Medicine and Drug Discovery
  • Online ISBN: 9780511976087
  • Book DOI: https://doi.org/10.1017/CBO9780511976087
Please enter your name
Please enter a valid email address
Who would you like to send this to *

CAPTCHA *

Skip to the audio challenge
×
References
,Biomarkers Definitions Working Group. (2001). Biomarkers and surrogate endpoints: Preferred definitions and conceptual framework. Clin. Pharmacol. Ther. 69, 89–95.
Horstmann, E, McCabe, MS, Grochow, L, Yamamoto, S, Rubinstein, L, Budd, T, et al. (2005). Risks and benefits of phase 1 oncology trials, 1991 through 2002. N. Engl. J. Med. 352, 895–904.
Calabrese, EJ. (2005). Cancer biology and hormesis: Human tumor cell lines commonly display hormetic (biphasic) dose responses. Crit. Rev. Toxicol. 35(6), 463–582.
Kola, I, & Landis, J. (2004). Can the pharmaceutical industry reduce attrition rates? Nat. Rev. Drug Discovery. 3, 711–716.
Heldin, C-H, Rubin, K, Pietras, K, & Östman, A. (2004). High interstitial fluid pressure – an obstacle in cancer therapy. Nat. Rev. Cancer. 4, 806–813.
Jain, RK. (1998). The next frontier of molecular medicine: Delivery of therapeutics. Nat. Med. 4, 655–657.
Fletcher, JI, Haber, M, Henderson, MJ, & Norris, MD. (2010). ABC transporters in cancer: More than just drug efflux pumps. Nat. Rev. Cancer. 10, 147–156.
Munn, LL. (2003). Aberrant vascular architecture in tumors and its importance in drug-based therapies. DDT 8 (9), 396–403.
Therasse, P, Arbuck, SG, Eisenhauer, EA, Wanders, J, Kaplan, RS, Rubinstein, L, et al. (2000). New guidelines to evaluate the response to treatment in solid tumors: European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J. Natl. Cancer Inst. 92, 205–216.
Michaelis, LC, & Ratain, MJ. (2006). Measuring response in a post-RECIST world: From black and white to shades of grey. Nat. Rev. Cancer. 6, 409–414.
Hillner, BE, Siegel, BA, Shields, AF, Liu, D, Gareen, IF, Hunt, E, et al. (2008). Relationship between cancer type and impact of PET and PET/CT on intended management: Findings of the National Oncologic PET Registry. J. Nuclear Med. 49(12), 1928–1935.
Nagrath, S, Sequist, LV, Maheswaran, S, Bell, DW, Irimia, D, Ulkus, L, et al. (2007). Microchip-based isolation of rare circulating epithelial cells in cancer patients. Nature. 450, 1235–1239.
Amado, RG, Wolf, M, Peeters, M, Cutsem, E, Siena, S, Freeman, DJ, et al. (2008). Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer. J. Clin. Oncol. 26, 1626–1634.
Khambata-Ford, S, Garrett, CR, Meropol, NJ, Basik, M, Harbison, CT, Wu, S, et al. (2007). Expression of epiregulin and amphiregulin and K-ras mutation status predict disease control in metastatic colorectal cancer patients treated with cetuximab. J. Clin. Oncol. 25, 3230–3237.
Ross, JS, & Fletcher, JA. (1999). The HER-2/Neu oncogene: Prognostic factor, predictive factor and target for therapy. Semin. Cancer Biol. 9(2), 125–138.
Kwak, EL, Camidge, DR, Clark, J, Shapiro, GI, Maki, RG, Ratain, MJ, et al. (2009). Clinical activity observed in a phase I dose escalation trial of an oral c-met and ALK inhibitor, PF-02341066. Journal of Clinical Oncology, ASCO Annual Meeting Proceedings. 27(15S), 3509.
Ratain, MJ, & Sargent, DJ. (2009). Optimising the design of phase II oncology trials: The importance of randomization. Eur. J. Cancer. 45, 275–280.
Cancel
Confirm
×