TY - JOUR
T1 - Trials and tribulations of interrogating biomarkers to define efficacy of cancer risk reductive interventions
AU - Brenner, Dean E.
AU - Hawk, Ernest
PY - 2013/2
Y1 - 2013/2
N2 - 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.
AB - 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.
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U2 - 10.1158/1940-6207.CAPR-12-0499
DO - 10.1158/1940-6207.CAPR-12-0499
M3 - Review article
C2 - 23333813
AN - SCOPUS:84874486867
SN - 1940-6207
VL - 6
SP - 71
EP - 73
JO - Cancer Prevention Research
JF - Cancer Prevention Research
IS - 2
ER -