2. Academic Validation
  3. Functional dissection of the KRAS G12C mutation by comparison among multiple oncogenic driver mutations in a lung cancer cell line model

Functional dissection of the KRAS G12C mutation by comparison among multiple oncogenic driver mutations in a lung cancer cell line model

  • Biochem Biophys Res Commun. 2021 Jan 1;534:1-7. doi: 10.1016/j.bbrc.2020.11.110.
Keigo Kobayashi 1,  Hideki Terai 2,  Hiroyuki Yasuda 1,  Junko Hamamoto 3,  Yuichiro Hayashi 4,  Osamu Takeuchi 5,  Yoichiro Mitsuishi 6,  Keita Masuzawa 1,  Tadashi Manabe 1,  Shinnosuke Ikemura 7,  Ichiro Kawada 1,  Yukio Suzuki 8,  Kenzo Soejima 9,  Koichi Fukunaga 1
Affiliations

Affiliations

  • 1 Division of Pulmonary Medicine, Department of Medicine, Keio University, School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.
  • 2 Division of Pulmonary Medicine, Department of Medicine, Keio University, School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan; Clinical and Translational Research Center, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan; Division of Bioreguratory Medicine, Kitasato University School of Pharmacy, 5-9-1, Shirokane, Minato-ku, Tokyo, 108-8641, Japan. Electronic address: [email protected].
  • 3 Division of Pulmonary Medicine, Department of Medicine, Keio University, School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan; Division of Bioreguratory Medicine, Kitasato University School of Pharmacy, 5-9-1, Shirokane, Minato-ku, Tokyo, 108-8641, Japan.
  • 4 Department of Diagnostic Pathology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.
  • 5 BioMedical Laboratory, Department of Research, Kitasato University, Kitasato Institute Hospital, 5-9-1, Shirokane, Minato-ku, Tokyo, 108-8642, Japan.
  • 6 Division of Pulmonary Medicine, Department of Medicine, Juntendo University, School of Medicine, 2-1-1, Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan.
  • 7 Division of Pulmonary Medicine, Department of Medicine, Keio University, School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan; Keio Cancer Center, Keio University, School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.
  • 8 Division of Bioreguratory Medicine, Kitasato University School of Pharmacy, 5-9-1, Shirokane, Minato-ku, Tokyo, 108-8641, Japan.
  • 9 Division of Pulmonary Medicine, Department of Medicine, Keio University, School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan; Clinical and Translational Research Center, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.
PMID: 33302159 DOI: 10.1016/j.bbrc.2020.11.110
Abstract

The development of molecular targeted therapy has improved clinical outcomes in patients with life-threatening advanced lung cancers with driver oncogenes. However, selective treatment for KRAS-mutant lung Cancer remains underdeveloped. We have successfully characterised specific molecular and pathological features of KRAS-mutant lung Cancer utilising newly developed cell line models that can elucidate the differences in driver oncogenes among tissues with identical genetic backgrounds. Among these KRAS-mutation-associated specific features, we focused on the IGF2-IGF1R pathway, which has been implicated in the drug resistance mechanisms to AMG 510, a recently developed selective inhibitor of KRAS G12C lung Cancer. Experimental data derived from our cell line model can be used as a tool for clinical treatment strategy development through understanding of the biology of lung Cancer. The model developed in this paper may help understand the mechanism of Anticancer drug resistance in KRAS-mutated lung Cancer and help develop new targeted therapies to treat patients with this disease.

Keywords

AMG510; IGF1R; KRAS G12C; Lung cancer.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-114277
    99.94%, KRAS G12C Inhibitor
    Ras