Developments for Personalized Medicine of Lung Cancer Subtypes: Mass Spectrometry-Based Clinical Proteogenomic Analysis
Molecular therapies targeting lung cancers with mutated epidermal growth factor receptor (EGFR) by EGFR-tyrosin kinase inhibitors (EGFR-TKIs), gefitinib and erlotinib, changed the treatment system of lung cancer. It was revealed that drug efficacy differs
- PDF / 1,514,055 Bytes
- 23 Pages / 504.57 x 720 pts Page_size
- 45 Downloads / 160 Views
Developments for Personalized Medicine of Lung Cancer Subtypes: Mass Spectrometry-Based Clinical Proteogenomic Analysis of Oncogenic Mutations Toshihide Nishimura and Haruhiko Nakamura
Abstract
Molecular therapies targeting lung cancers with mutated epidermal growth factor receptor (EGFR) by EGFR-tyrosin kinase inhibitors (EGFR-TKIs), gefitinib and erlotinib, changed the treatment system of lung cancer. It was revealed that drug efficacy differs by race (e.g., Caucasians vs. Asians) due to oncogenic driver mutations specific to each race, exemplified by gefitinib / erlotinib. The molecular target drugs for lung cancer with anaplastic lymphoma kinase (ALK) gene translocation (the fusion gene, EML4ALK) was approved, and those targeting lung cancers addicted ROS1, RET, and HER2 have been under development. Both identification and quantification of gatekeeper mutations need to be performed using lung cancer tissue specimens obtained from patients to improve the treatment for lung cancer patients: (1) identification and quantitation data of targeted mutated proteins, including investigation of mutation heterogeneity within a tissue; (2) exploratory mass spectrometry (MS)-based clinical proteogenomic analysis of mutated proteins; and also importantly (3) analysis of dynamic protein–protein interaction (PPI) networks of proteins significantly related to a subgroup of patients with lung cancer not only with good efficacy but also with acquired resistance. MS-based proteogenomics is a promising approach to directly capture mutated and fusion proteins expressed in a clinical sample. Technological developments are further expected, which will provide a powerful solution for the stratification of patients and drug discovery (Precision Medicine).
T. Nishimura (*) Translational Medicine Informatics, St. Mariana University School of Medicine, Kanagawa, Japan Research & Development, Biosys Technologies Inc., Tokyo, Japan
H. Nakamura Translational Medicine Informatics, St. Mariana University School of Medicine, Kanagawa, Japan
Center of Excellence in Biological and Medical Mass Spectrometry, BMC, Lund University, Lund, Sweden e-mail: [email protected]
Chest Surgery, St. Mariana University School of Medicine, Kanagawa, Japan e-mail: [email protected]
© Springer International Publishing Switzerland 2016 Á. Végvári (ed.), Proteogenomics, Advances in Experimental Medicine and Biology 926, DOI 10.1007/978-3-319-42316-6_8
115
T. Nishimura and H. Nakamura
116
Keywords
Lung adenocarcinoma • Clinical proteogenomics • Oncogenic driver mutation • Fusion gene • Mass spectrometry (MS) • Third-generation EGFR tyrosine kinase inhibitor (TKI) • Protein-protein interaction (PPI) network • Drug resistance • Precision medicine
8.1
Introduction
Lung cancer is the most prevalent type of cancer in the world and it is a leading cause of death (Jemal et al. 2011; the data base of Japanese Ministry of Health and Labor and Welfare 2013). In Japan, annual deaths from lung cancer are increasing and currently approach 70,000 (The data
Data Loading...
