The World’s First Successful Development of a Screening Platform that Promotes the Discovery of Cancer Preventive Drugs

By identifying small chemical compounds that promote the anti-tumor activity of normal epithelial cells, the elimination of transformed cells from normal cell layers is promoted.

Key Points
・First successful development of a small chemical compound screening assay platform1 that promotes the discovery of cancer preventive drugs.・The research group was highly original in focusing on the anti-tumor activity2 of normal epithelial cells that does not involve the immune system.

・It was verified that the small chemical compounds that were identified by using this screening platform actually do promote extrusion of transformed cells from normal cell layers.

Overview

By focusing on the anti-tumor activity of normal epithelial cells, we have succeeded for the first time in the world in constructing a small chemical compound screening assay platform that can lead to the discovery of cancer preventive drugs. Furthermore, we verified that the small chemical compounds that were identified by screening with this platform promote the extrusion of transformed cells from normal cell layers.

This research was conducted with a grant-in-aid from the Creation of Innovation Centers for Advanced Interdisciplinary Research Areas Program of the Ministry of Education, Culture, Sports, Science, and Technology.

Background

One out of three Japanese persons dies of cancer. In order to improve cancer therapy, early detection and prophylactic treatment is a must. However, at present, there exists no cancer prophylactic medicine of which effect has been scientifically proven.

When malignant cancer occurs in humans, multiple carcinogenic mutations accumulate in cells. In many cases our bodies harbor precancerous lesions that have a small number of mutations, but so far no treatment methods have been found for prophylactically eliminating them. In the latest research, our research group has clarified that, at the very early cancer stage, normal cells have the ability to recognize neighboring transformed cells and actively eliminate them.

Research Methods

Our research group has used a mammalian cell culture system that was uniquely established in prior research, to work toward the establishment of a screening platform to identify small chemical compounds that promote the anti-tumor activity of normal epithelial cells. The effect of the small chemical compounds that were identified by the screening was verified in the mammalian cultivated cell culture system and in a mouse organ culture system.

Research Results

We have succeeded in establishing a screening platform for small chemical compounds that have the effect of promoting the elimination of transformed cells from normal cell layers. In addition, by performing screening with this platform, we have identified VC1-8, which is a derivative of Rebeccamycin3, and we have verified that VC1-8 has the effect of promoting the elimination of transformed cells.

Anticipated Outcomes

At this time there is no cancer preventive medicine whose effect has been scientifically demonstrated. We believe that further development of the research presented at this time will result in the discovery of cancer preventive medicines in the near future, leading to the use of medicines to prevent cancer.