A/Prof. Johnny ONG National Cancer Centre Singapore Link to biosketch

Abstract

Peritoneal carcinomatosis (PC) is a common form of metastases for many gastrointestinal and uro-gynaecological malignancies. The tumour microenvironment in PC is largely composed of tumour cells, other cell types such as stromal and immune cells, as well as ascites, which is the fluid component of the tumour microenvironment. Much of the research performed in the recent years have focused on the cellular components of the tumour, using multi-omics technology to decipher genomic and transcriptomic profiles of PC. However, little emphasis has been placed on the fluid microenvironment. Enriched in paracrine factors, the fluid microenvironment has the potential to be exploited for the development of novel therapeutic options for PC. Our group in the Laboratory of Applied Human Genetics in the National Cancer Centre Singapore has recently demonstrated that PC tumour cells are addicted to paracrine factors found within the fluid microenvironment of the peritoneal cavity. We termed this phenomenon “paracrine addiction” and demonstrated proof of concept that direct inhibition of a key paracrine ligand was therapeutically efficacious. Additionally, the contribution of immune and stromal cells in tumour metastasis goes beyond paracrine addiction. We propose that identification of key paracrine ligands found within the fluid microenvironment in conjunction with the understanding of the biology of tumour cells, may provide the foundation to a paradigm shift in the way PC can be treated.