title: Trials and tribulations of interrogating biomarkers to define efficacy of cancer risk reductive interventions.
abstract: The challenges of clinical screening of cancer risk reductive interventions ("chemopreventive") have slowed progress in deployment of therapeutics to reverse or delay the carcinogenesis process. The preoperative or window-of-opportunity design clinical trial design enrolls subjects rapidly, has short study periods, and quantifies tissue biomarkers that reflect both anti-carcinogenesis mechanism of the risk reductive intervention and key molecular events of the carcinogenesis process for a specific epithelial target. High subject screened to on study ratios reduce the efficiency and increase cost of this research strategy. Small-sized tissue samples obtained by minimally invasive endoscopic technologies limit the number of biomarkers that can be detected and quantified, forcing investigators into choosing either a broad-based but superficial multi-mechanism exploration of signaling intermediates or a more focused analysis of multiple molecular events in a linear signaling-specific pathway. More efficient strategies of the future might involve isolation and expansion of pluripotent cells from at-risk epithelium or intraepithelial neoplastic lesions. Such a strategy would allow interrogation of key carcinogenesis-associated pathways and mechanisms in representative primary single-cell cultures amenable to genomic, proteomics, or transfection-based technologies.
authors: Departments of Internal Medicine and Pharmacology, University of Michigan, Ann Arbor, USA. dbrenner@umich.edu
authors: Dean E
authors: DE
authors: Brenner
authors: Ernest
authors: E
authors: Hawk
mesh_terms: D000236:Adenoma / Q000188:drug therapy* / Q000601:surgery*; D000493:Allopurinol / Q000008:administration & dosage*; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000601:surgery*; D005260:Female; D006801:Humans; D008297:Male; D011300:Preoperative Care
chemical_list: D000964:Antimetabolites, Antineoplastic; D000493:Allopurinol