• Gary J Kelloff and Caroline C Sigman.
• Division of Cancer Treatment and Diagnosis, Cancer Imaging Program, National Cancer Institute, Executive Plaza North Room 6038, 9000 Rockville Pike, Bethesda, MD 20892, USA. kelloffg@mail.nih.gov
• Eur. J. Cancer. 2005 Mar 1; 41 (4): 491-501.

AbstractAlthough several new oncology drugs have reached the market, more than 80% of drugs for all indications entering clinical development do not get marketing approval, with many failing late in development often in Phase III trials, because of unexpected safety issues or difficulty determining efficacy, including confounded outcomes. These factors contribute to the high costs of oncology drug development and clearly show the need for faster, more cost-effective strategies for evaluating oncology drugs and better definition of patients who will benefit from treatment. Remarkable advances in the understanding of neoplastic progression at the cellular and molecular levels have spurred the discovery of molecularly targeted drugs. This progress along with advances in imaging and bioassay technologies are the basis for describing and evaluating new biomarker endpoints as well as for defining other biomarkers for identifying patient populations, potential toxicity, and providing evidence of drug effect and efficacy. Definitions and classifications of these biomarkers for use in oncology drug development are presented in this paper. Science-based and practical criteria for validating biomarkers have been developed including considerations of mechanistic plausibility, available methods and technology, and clinical feasibility. New promising tools for measuring biomarkers have also been developed and are based on genomics and proteomics, direct visualisation by microscopy (e.g., confocal microscopy and computer-assisted image analysis of cellular features), nanotechnologies, and direct and remote imaging (e.g., fluorescence endoscopy and anatomical, functional and molecular imaging techniques). The identification and evaluation of potential surrogate endpoints and other biomarkers require access to and analysis of large amounts of data, new technologies and extensive research resources. Further, there is a requirement for a convergence of research, regulatory and drug developer thinking - an effort that will not be accomplished by individual scientists or research institutions. Research collaborations are needed to foster development of these new endpoints and other biomarkers and, in the United States (US), include ongoing efforts among the Food and Drug Administration (FDA), National Cancer Institute (NCI), academia, and industry.

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