Whole Genome Sequencing Finds Therapeutic Targets for Linitis Plastica-type Gastric CancerProspects towards developing treatments for intractable cancer

17 August 2021

National Cancer Center Japan
Keio University School of Medicine
Japan Agency for Medical Research and Development

in Japanese

Highlights

A group comprising Division of Cellular Signaling (Chief: Hiroyuki Mano) and Department of Translational Oncology, Fundamental Innovative Oncology Core (Chief: Fumitaka Takeshita) at the Research Institute, National Cancer Center Japan (President: Hitoshi Nakagama) and Department of Pathology, Keio University School of Medicine (Professor Yae Kanai) analyzed the whole genome of cancerous cells of ascitic fluids to elucidate the carcinogenic mechanism of linitis plastica-type (also known as scirrhous-type) gastric cancer (LPGC) and to look for targets for its treatment. LPGC is difficult to treat, and little is known of its associated genetic alterations.

The study found many genetic abnormalities associated with LPGC, a quarter of them very likely to respond to molecularly targeted drugs already available. Model mice were implanted with cell lines derived from cancerous cells from the ascites. When specific inhibitors were given, suppression of cancer progression or disappearance of peritoneal dissemination was observed.

Rarely diagnosed early, and often disseminating in the peritoneal cavity, LPGC treatments are challenging, summoning measures to contain peritoneal dissemination, and for prevention. The findings will be directly taken to a wide range of clinical development, from off-label use of molecular targeting drugs, to implementation in cancer gene panel tests and to developing novel compounds.

The results have been published online at Nature Cancer on 17 August 2021.

Prospects

The study found detailed genomic information on LPGC, of which highly amplified genes in the receptor-type tyrosine kinase-RAS-MAPK pathway stand out. As mouse models responded to corresponding targeted drugs, inclusion in cancer gene panel tests and development of target drugs are anticipated. A TEAD pathway inhibitor could be the new LPGC treatment drug.

Publication

Journal

Nature Cancer

Title

Multi-omics profiling of peritoneal metastases in gastric cancer identifies molecular subtypes and therapeutic vulnerabilities

Authors

Yosuke Tanaka, Fumiko Chiwaki, Shinya Kojima, Masahito Kawazu, Masayuki Komatsu, Toshihide Ueno, Satoshi Inoue, Shigeki Sekine, Keisuke Matsusaki, Hiromichi Matsushita, Narikazu Boku, Yae Kanai, Yasushi Yatabe, Hiroki Sasaki, Hiroyuki Mano

DOI

10.1038/s43018-021-00240-6

URL

https://www.nature.com/articles/s43018-021-00240-6 (linked at external link)

Support

The following funding from Japan Agency for Medical Research and Development (AMED) were utilized for this research:

• Elucidation of initiation and progression mechanism of human epithelial tumors towards identification of novel therapeutic targets, Project for Cancer Research and Therapeutic Evolution
• Development of advanced medical technology for cancer, psychiatric disorders and renal diseases by multi-omics analyses, Research on Development of New Drugs

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