From cancer genomics to thoracic oncology: discovery of new biomarkers and therapeutic targets for lung and esophageal carcinoma.
Over the last decade, many genetic and epigenetic alterations involved in the development and progression of lung and esophageal cancers have been reported, but their precise molecular mechanisms have remained unclear. Although novel drugs targeting some of these molecular targets have been developed, they provide limited survival benefits to only a small subset of cancer patients, and only a small number of practically useful biomarkers are presently available. To identify the molecules involved in lung and esophageal carcinogenesis and those applicable as novel tumor biomarkers and for the development of new molecular therapies, we performed gene expression profile analysis of 101 archived lung cancers and 19 esophageal squamous cell carcinomas whose tumor cells were purified by laser microdissection. Through a subsequent systematic approach using tissue microarray, RNA interference, and high throughput enzyme-linked immunosorbent assay techniques as well as bioinformatics, we have identified a set of molecules that fall into the category of oncoantigens. These molecules are potentially promising candidates for the development of novel diagnostic biomarkers, therapeutic drugs, and/or immunotherapy; there is also a small subset of biomarkers for predicting the presence of lymph node metastasis in surgically treated patients. In this article, we introduce our sophisticated and integrated cancer genomics strategy for improving the treatment of cancer patients.
Daigo
Yataro
Y
Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
Nakamura
Yusuke
Y
D000970:Antineoplastic Agents / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics*; D019496:Cancer Vaccines / Q000627:therapeutic use; D002294:Carcinoma, Squamous Cell / Q000737:chemistry / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D019295:Computational Biology; D004797:Enzyme-Linked Immunosorbent Assay; D004938:Esophageal Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D023281:Genomics / Q000639:trends; D006801:Humans; D008175:Lung Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D008207:Lymphatic Metastasis; D008495:Medical Oncology / Q000639:trends; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis; D018579:Patient Selection; D010455:Peptides / Q000627:therapeutic use; D011379:Prognosis; D034622:RNA Interference
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D019496:Cancer Vaccines; D010455:Peptides