Hokkaido University Research Profiles

Life Sciences

Susceptibility Testing of Molecular-targeted Therapeutic Drugs

Visualization technique of drug responsiveness in individual cells using fluorescence bioimaging

Fluorescence bioimaging is a technique to visualize the cell behavior at the single cell level. Using this method, we have applied the imaging technology to visualize drug responsiveness and resistance, and to predict future drug responsiveness of patients.

Content of research

This diagnostic technique uses fluorescent proteins and a fluorescent biosensor based on the principle of F?rster resonance energy transfer (FRET).
By visualizing the drug responsiveness at the single cell level with this biosensor, it has become possible to detect a very small number of drug-resistant cells. As a result, we have achieved a high concordance rate with the clinical course after administration and prediction of future drug responsiveness, both of which were not possible with conventional technology. This technology is not only the world’s first clinical application of fluorescent proteins, but also expected to help assure safety by selecting therapies with guaranteed efficacy. This will also bring economic benefits to medicine by reducing the financial burden on patients and the medical costs. We are now proceeding with this project for chronic myeloid leukemia, which is a blood cancer, as a model. In principle, this technology can be applied to various cancers.

  • Pickles, a fluorescent biosensor for the measurement of BCR-ABL activity

  • Assessment of drug efficacy using Pickles at the single cell level

  • Examples of drug efficacy assessment using this technology. The course of cases determined to be susceptible and resistant with this test are shown in blue and red, respectively. The bold line shows the average of each.

Potential for social implementation

  • ・Prediction of drug responsiveness
  • ・Detection of drug-resistant cells
  • ・Early detection of cancer cells

Appealing points to industry and local governments

Research activities at the Department of Cell Physiology are focused on signal transduction studies using fluorescence bioimaging. Application of the knowledge obtained from these activities and the biosensors used there are also explored. The keyword is “Seeing is believing.”

Intellectual property related to this research

特願2015-511267  「フェルスター共鳴エネルギー移動用ポリペプチド」
特許第5665262号 「BCR-ABLチロシンキナーゼ活性測定試薬」