Cancer Epidemiology and Biomarkers:A Precision Medicine Research Strategy

作者:Curtis C. Harris, M.D.        期刊:2015年-11月(59期)


Curtis C. Harris, M.D.

       The Precision Medicine Research strategy relies on the generation of validated Biomarkers with which to better classify patients and redefine disease taxonomy. Non-small cell lung Cancer patients can now be classified into new subgroups (taxa)based on whether their tumors contain genomic alternations, e.g., in the EGFR or ALK genes and are then eligible for EG⁃FR- or ALK-targeting chemotherapeutics, respectively.


        Advances like these have arisen from improvements in genomic technologies. Other“ -omics” continue to improve and, while only genomic biomarkers are currently used in the clinical management of lung cancer, candidate biomarkers from these other“-omics” are beginning to ac⁃cumulate. Biomarkers can be measured in isolation or added to other validated bio⁃markers to form a biomarker panel. Progress in statistical methodologies has recently allowed for the de novo combination of multiple- “omic” types into putative bio⁃marker panels that promise to be more comprehensive than single-“omics” biomarkers. Using “omics” technologies to generate biomarkers for use in Precision Medicine is currently limited by : ① a lack of large international datasets with“-omics” measurements for validation/longitudinal studies, ②statistical concerns (false positives and lack of power), ③technical reproducibility issues between labs and 4) the need for improved reference libraries. Lung cancer screening and detection of early lung cancer lesions is expected to increase and high false discovery rates associated with low dose CT can lead to over diagnosis; thus necessitating the generation of biomarkers to precisely classify ear⁃ly stage lung cancer patients into those who require surgery only and those who might benefit from surgery with adjuvant treatment.


        Dr. Harris is being recognized for his landmark scientific contributions to the fields of integrative and molecular Epidemiology of human cancer and cancer bio⁃markers. He is particularly renowned for his pioneering studies of gene-environment interactions. For example, his labora⁃tory was one of the first to document the link between the environmental carcinogen aflatoxin B1 and a specific mutation in the TP53 tumor suppressor gene in patients with hepatocellular carcinoma from Qidong, China. They also discovered that secondhand smoke exposure during childhood is associated with increased lung can⁃cer risk among never smokers, particularly those carrying a certain genetic variation in their MBL2 gene. His research on environmental carcinogenesis has significantly impacted the field of cancer risk assessment and our understanding of the molecular pathogenesis of human cancer. (Edited by Yichu Ye).