Characterising tumour heterogeneity to improve cancer therapies

Cell heterogeneity in tumours: a barrier to cancer treatment

Tumours are cell clusters that proliferate anarchically due to multiple alterations, especially at the genetic level. Recent progress in deciphering these alterations has led to the development of new targeted compounds to treat advanced cancers, which have permitted the development of some individualised cancer therapies. Unfortunately, the performance of these targeted therapies has not reached initial expectations and advanced tumours frequently reappear after treatment cessation, resulting in very low survival rates for patients.

Genetic and post-genetic differences between cells of a same tumour are one of the reasons for the lack of performance of targeted therapies. Some cells may indeed have molecular characteristics that allow them to be more resistant to therapy. As such, while a treatment will give the impression of effectively curing the disease, these few resistant cells will persist, proliferate, and give rise to a new tumour. The characterisation of cell diversity within a tumour is therefore essential to treat it effectively.

A French-Australian laboratory to better understand the heterogeneity of tumours

Researchers at the International Associated Laboratory (LIA) Heterogeneity of Tumours in Metastatic Cancers are working on this issue. Supported by INSERM and co-directed by Prof. Frédéric Hollande of the University of Melbourne in Australia, and by Profs. Alain Puisieux and Patrick Mehlen of the Lyon Cancer Research Centre (CRCL) in France, this French-Australian laboratory has the following objectives:

1. To analyse the impact of intra-tumour heterogeneity on the response to therapies;

2. To characterise the molecular mechanisms involved in resistance to tumour cell treatments;

3. To target such characterised mechanisms to prevent post-treatment relapses.

Since its creation in July 2017, this laboratory has made it possible to discover the role of several factors, such as the state of differentiation of cells or the content of the Claudine-2, in the genesis and maintenance of breast and colorectal tumours. Recently, the research conducted within this LIA has also highlighted the cellular mechanism underlying the chemotherapy resistance of a subgroup of colorectal cancers, opening the possibility of targeting this process to prevent resistance.

The LIA, a tool for international cooperation

Set up by the National Institute of Health and Medical Research (Inserm), the LIA structures its scientific cooperation around a joint research project between a French Inserm research team and an international team. Funded for a minimum period of 4 years, these laboratories make it possible to facilitate the mobility of researchers and students between the two countries, while funding a part of the research. There are currently several LIAs in Australia, such as the APICOLIPID laboratory on infectious diseases with the University of Melbourne, or the IntegrA laboratory on autism with the Royal Melbourne Institute of Technology (RMIT).

Cell heterogeneity in colorectal metastasis cancer. Colours by fluorescent markers allow to monitor the cells during their proliferation. Photo by C. Shembrey and Frédéric Hollande.