Development of novel biomarker for cetuximab therapy in lung cancer

2011 Fiscal Year Final Research Report

• Project/Area Number: 21590994
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Respiratory organ internal medicine
• Research Institution: Tottori University
• Principal Investigator: CHIKUMI Hiroki 鳥取大学, 医学部, 講師 (90283994)
• Co-Investigator(Kenkyū-buntansha): SHIMIZU Eiji 鳥取大学, 医学部, 教授 (50187449)
• Project Period (FY): 2009 – 2011
• Keywords: 肺癌 / 薬剤反応性

Research Abstract

An anti-EGFR monoclonal antibody, cetuximab, has been developed as a novel molecular targeting therapy in lung cancer. In this study, we developed a novel biomarker for cetuximab to select the subset of patients who will show a meaningful clinical response, by using our original finding that the main anti-cancer mechanism of cetuximab is immunological antitumor activity such as antibody-dependent cellular cytotoxicity(ADCC). As a result, we revealed that ULBP2 is the most significant NKG2D ligands, which are known as the activating ligands of NK cells, and that soluble form of ULBP2(sULBP2) directly suppresses both the cytolytic activity and cetuximab induced ADCC activity of host NK cells. Therefore, administration of cetuximab to the patients with low levels of sULBP, or the patients after surgery or chemotherapy with lowest sULBP2 levels is the best strategy for cetuximab treatment for lung cancer.

Research Products

• [Journal Article] Diagnostic and Prognostic Impact of Serum Soluble UL16-Binding Protein 2 in Lung Cancer Patients (2012)
  • Author(s): Yamaguchi K, Chikumi H, Shimizu A, Takata M, Kinoshita N, Hashimoto K, Nakamoto M, Matsunaga S, Kurai J, Miyake N, Matsumoto S, Watanabe M, Yamasaki A, Igishi T, Burioka N, Shimizu E
  • Journal Title: Cancer Science Volume: (in press)
  • DOI: DOI:10.1111/j.1349-7006.2012.02330.x
  • Peer Reviewed
• [Journal Article] Lack of AKT activation in lung cancer cells with EGFR mutation is a novel marker of cetuximab sensitivity (2012)
  • Author(s): Takata M, Chikumi H, Miyake N, Adachi K, Kanamori Y, Yamasaki A, Igishi T, Burioka N, Nanba E, Shimizu E
  • Journal Title: Cancer Biol Ther Volume: 13 Pages: 369-378
  • URL: http://dx.doi.org/10.4161/cbt.19238
  • Peer Reviewed
• [Journal Article] Rapamycin induces p53-independent apoptosis through the mitochondrial pathway in non-small cell lung cancer cells Oncology reports
  • Author(s): Miyake N, Chikumi H, Takata M, Nakamoto M, Igishi T, Shimizu E
  • Volume: (in press)
  • URL: http://www.ncbi.nlm.nih.gov/pubmed/22313637
  • Peer Reviewed
• [Presentation] Antibody-dependent cellular cytotoxicity mediated by cetuximab against mesothelioma cells (2010)
  • Author(s): Chikumi H, Kurai J, Kinoshita N, Nakamoto M, Matsumoto S, Igishi T, Hamada H, Yano S, Shimizu E
  • Organizer: The 10th international conference of the international mesothelioma interest group(Workshop : Immunotherapy : bench to bedside-II)
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 2010-09-02
• [Presentation] Soluble UL16 binding protein 2 is elevated in the sera of lung cancer patients (2010)
  • Author(s): Yamaguchi K, Chikumi H, Kinoshita N, Shimizu A, Hashimoto K, Kurai J, Yamasaki A, Nakamoto M, Matsumoto S, Takata M, Igishi T, Burioka N, Shimizu E
  • Organizer: American Association for Cancer Research 101st Annual Meeting 2010
  • Place of Presentation: Washington DC, USA
  • Year and Date: 2010-04-20
• [Presentation] Biomarkers of immunological therapy of lung cancer (2009)
  • Author(s): Chikumi, H., Shimizu, E
  • Organizer: 第49回日本呼吸器学会学術講演会
  • Place of Presentation: 東京
  • Year and Date: 2009-06-13