The National Clinical Target Validation Laboratory (NCTVL) was established in FY2006 at the request of the Division of Cancer Treatment & Diagnosis (DCTD), NCI, for its collaboration with the Center for Cancer Research (CCR) to address the mechanistic gap in oncologic drug development that frequently occurs due to the difficulties inherent in determining the effect of a therapeutic intervention on its putative site of action in patients. The laboratory serves as an alpha site for the elucidation of novel target tissue methodologies specifically applicable to human cancer Phase 0 and Phase I/II clinical trials in the CCR Developmental Therapeutics Clinic, confirming the therapeutic effects of small molecule anticancer agents on specific signal transduction pathways of interest in humans that were observed during preclinical development. As part of the DCTD's early therapeutics clinical development program, the NCTVL also serves as a national resource for early clinical trials in the extramural clinical cancer research community by providing validated assay procedures and/or access to laboratory and/or clinical resources that are critically needed to evaluate molecular targets of interest. The mission of the NCTVL is to conduct validated assay procedures to test tumor or surrogate tissues for effects of molecularly targeted therapies. Within the NCTVL, SAIC-Frederick, Inc., provides scientific expertise in the development, testing, and further refinement of novel methodologies for use in target tissues specifically applicable to human cancer clinical trials. The laboratory assesses drug effects on molecular targets in patients treated within the CCR using validated target assays, many of which will be transferred from the pharmacodynamic assay development and implementation section of the Laboratory of HumanToxicology and Pharmacology. Essential to the evaluation of drug efficacy, the laboratory creates and develops QA/QC programs for correlative clinical investigations that utilize small, and difficult to obtain, patient specimens, and then assists investigators in acquiring the necessary skills and expertise to allow transfer of the validated laboratory procedures for their own investigations at NCI-designated clinical cancer research venues (NCI-funded Phase I and II programs, Cancer Centers, Cooperative Groups, andSPORES). It also provides target validation assays for patient samples from NCI-funded extramural investigators lacking the resources or expertise to conduct such assays on site.