Clinical trials and biomarker development with molecularly targeted agents and radiotherapy Neesha Dhani & Lillian L. Siu Published online: 1 April 2008 # Springer Science + Business Media, LLC 2008 Abstract Introduction The conventional paradigm of drug develop- ment used for cytotoxic chemotherapeutic agents may not represent the most effective method of assessing the safety and biological activity of molecularly targeted agents, given that the latter may offer improved therapeutic indices with less toxic effects on normal tissues. Objectives With the number of novel therapeutics in oncology entering the investigative arena, there is a need to expedite the drug development process by allowing for optimal selection of agents with the greatest likelihood of having clinical benefit over those of lower potential utility. Discussion The high throughput techniques now available in genomic, proteomic and metabolomic profiling should allow for more effective preclinical investigation with the identification of biomarkers or indicators of treatment response, leading to increased clinical efficacy with appropriate patient selection. Conclusion With this in mind, current investigation should be directed at validating novel endpoints in order to accelerate the drug development and approval process with targeted therapeutics in oncology. Keywords Clinical trials . Biomarker . Radiotherapy . Genomics . Prognosis . Pharmacokinetics 1 Introduction The National Institute of Health working group defines biomarkers as characteristics that can be objectively measured and evaluated as indicators of normal physiologic or pathologic processes, or as pharmacologic responses to a therapeutic intervention [1]. They can be clinically applied to all stages of disease presentation and treatment from screening and diagnosis to prognostication and monitoring of response to therapeutic intervention. Within the spectrum of oncology drug development, the primary purposes of biomarkers are to assist in deriving the optimal dose and schedule of a therapeutic agent or regimen with acceptable toxicity, to determine if the agent of interest is producing its intended biological effect in its target population and finally, to help predict for therapeutic clinical benefit. Biomarkers as applied to oncology consist of a hetero- geneous group of characteristics and include molecular and biochemical entities such as proteins, nucleic acids (DNA and RNA), lipids and small metabolites as well as on a larger scale, biophysical profiles of whole cells or tissues. The methods of quantification and analysis are just as varied, ranging from genomic assays such as DNA sequencing and epigenetic analysis, to protein and proteo- mic assays such as immunohistochemistry (IHC) and mass spectrometry (MS), to whole body assessment with novel technologies in biomedical imaging. With the significant increase in available options for biomarker characterization and evaluation there is optimism that effective biomarker use will expedite the drug development process in oncology Cancer Metastasis Rev (2008) 27:339–349 DOI 10.1007/s10555-008-9140-0 N. Dhani : L. L. Siu Princess Margaret Hospital, Division of Medical Oncology and Hematology, Department of Medicine, University of Toronto, Toronto, ON, Canada L. L. Siu (*) Princess Margaret Hospital, Division of Medical Oncology and Hematology, 610 University Ave., 5th Floor, Room 718, Toronto, ON M5G 2M9, Canada e-mail: Lillian.Siu@uhn.on.ca