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Developments for Personalized Medicine of Lung Cancer Subtypes: Mass Spectrometry-Based Clinical Proteogenomic Analysis of Oncogenic Mutations

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Proteogenomics

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 926))

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, EML4-ALK) 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).

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Acknowledgments

TN and HN thank Professor Emeritus Dr. Harubumi Kato at Tokyo Medical University for his valuable guidance regarding to clinical study designs, and Drs. Melinda Rezeli, Charlotte Welinder, Johan Malm, the late Thomas E. Fehniger, and György Marko-Varga at the Center of Excellence in Biological and Medical Mass Spectrometry, Biomedical Center, Lund University for their collaborative developments of MS-based technologies. TN especially thanks Dr. Ákos Végvári at Pharmacology & Toxicology, University of Texas Medical Branch, Galveston TX USA, for his instruction to MS-based protein-mutation studies by utilizing the MuPdb.

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Authors and Affiliations

  1. Translational Medicine Informatics, St. Mariana University School of Medicine, Kanagawa, Japan

    Toshihide Nishimura & Haruhiko Nakamura

  2. Research & Development, Biosys Technologies Inc., Tokyo, Japan

    Toshihide Nishimura

  3. Center of Excellence in Biological and Medical Mass Spectrometry, BMC, Lund University, Lund, Sweden

    Toshihide Nishimura

  4. Chest Surgery, St. Mariana University School of Medicine, Kanagawa, Japan

    Haruhiko Nakamura

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  1. Toshihide Nishimura
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Correspondence to Toshihide Nishimura .

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  1. Department of Pharmacology & Toxicology, University of Texas Medical Branch, Galveston, Texas, USA

    Ákos Végvári

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Nishimura, T., Nakamura, H. (2016). Developments for Personalized Medicine of Lung Cancer Subtypes: Mass Spectrometry-Based Clinical Proteogenomic Analysis of Oncogenic Mutations. In: Végvári, Á. (eds) Proteogenomics. Advances in Experimental Medicine and Biology, vol 926. Springer, Cham. https://doi.org/10.1007/978-3-319-42316-6_8

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