Annual Report 2023

Division of Cancer Therapeutics

Hideaki Ogiwara, Mariko Sasaki, Hinako Masuda, Shohei Takase, Keiko Nakazato, Harumi Hirano, Makoto Fukushima

Introduction

 We focus on gene mutations, which are characteristic of cancer, and aim to develop optimal cancer treatment methods according to the genetic mutations of each cancer patient. In particular, we are focusing on the fact that chromatin regulatory genes cause defective gene abnormalities in many cancers, including intractable cancers, and we are working on the search for promising cancer therapeutic targets specific to cancers in which these genes are deficient. We aim to establish new cancer treatments based on scientific evidence by identifying therapeutic targets based on genetic abnormalities in cancer and clarifying the mechanism of the phenomenon. Furthermore, we aim to realize clinical applications by consistently developing new drugs for therapeutic targets in collaboration with pharmaceutical companies.

The Team and What We Do

 We work on identifying promising therapeutic targets based on a loss-of-function mutation in refractory cancers.

Research Activities

 SMARCB1 is the causative gene of highly malignant childhood and juvenile cancers such as malignant rhabdoid tumors and epithelioid sarcoma. To date, we have identified promising target factors for SMARCB1-deficient cancers by developing a SMARCB1-deficient cancer cell line model and a unique synthetic lethal target search method. We elucidated the mechanism of action when the target is inhibited and submitted a paper on the results.

 Diffuse gastric cancer is an undifferentiated and highly malignant gastric cancer that is refractory to standard treatment drugs. In joint research with Dr. Hiroki Sasaki of FIOC, we identified a promising therapeutic agent for ARID1A-deficient diffuse gastric cancer using a cell line model derived from diffuse gastric cancer patients, elucidated its mechanism of action, and explored the construction of a pathological model of diffuse gastric cancer.

Education

 Young researchers were trained to participate in academic conferences.

Future Prospects

 Based on our research, we investigate drug discovery and development of our identified therapeutic targets. We hope that our research translates into clinical applications.