Creation of a tool for the study of new treatments for liver cancer

The team of Sylvain Meloche, professor at the Faculty of Medicine of the University of Montreal and director of the Cell Signaling and Growth Research Unit at the Institute for Research in Immunology and Cancer (IRIC), has designed a preclinical model for the study of the most common subtype of liver cancer.

The work, the results of which were published in the journal Disease Models & Mechanisms, was jointly conducted by research associate Laure Voisin and research advisor Marjorie Lapouge. Researcher Vincent Trinh, director of the IRIC Digital Histology and Advanced Pathology Research Unit, also contributed to the study.

In search of a clinically relevant study model

From left to right: Marjorie Lapouge, Sylvain Meloche and Laure Voisin

Credit: Mathilde Soulez

Liver cancer is a major health concern worldwide: it ranks sixth among the most common cancers and third in terms of cancer mortality. One subtype in particular, hepatocellular carcinoma (HCC), alone accounts for 80 to 90% of liver cancers. Often diagnosed at an advanced stage, ineffectively targeted by the few existing treatments, HCCs do not carry favorable prognoses for those affected.

The team in Sylvain Meloche’s laboratory wanted to fill a critical need in the development of new therapies targeting HCCs: the design of a preclinical model that mimics advanced human HCCs as closely as possible. To do this, the team established a cell line from genetically modified murine liver tumors: the HepYF line.

Reproduce the pathophysiological characteristics of aggressive and metastatic HCCs

Scientific creation named “Lunar Landscape”, by Marjorie Lapouge. Histological section of a cancerous liver. This creation is representative of the disorders and disturbances that occur in organs affected by cancer.

Credit: Marjorie Lapouge

Several advantages make the HepYF line a good model for the study of liver cancers. It allows to obtain tumors whose growth is rapid, predictable and reproducible, and which are representative of the most aggressive forms of metastatic HCC.

Furthermore, the HepYF line offers a syngeneic model: it comes from murine specimens that have the same genetic background as those into which it will be injected for carcinogenesis analyses or preclinical studies. Perceived as “self” by the immune system, it is one of the rare models that can analyze the immune response against the tumor and evaluate immunotherapy options.

With these characteristics, the HepYF model developed by Sylvain Meloche’s laboratory will allow us to better understand the pathogenesis of HCC. It will also be very useful for testing new molecules and immunotherapies that could improve the range of treatments available for liver cancers.

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