Disarm recalcitrants colorectal cancers


Cyril Corbet led the race this year: after receiving the Galen Prize for Pharmacology, he was named FNRS research associate. Quite a haul for this half-marathon enthusiast. And at the finish, always the same goal: to better understand tumour cell behaviour.



He doesn’t really know why he chose biology. It seemed self-evident. ‘I chose it already at the lycée.’ Mr Corbet is from Nantes. ‘There was no particular reason, no trigger.’ It was just one certainty that preceded another: studying cancer mechanisms. ‘I always focused on them, I never let go of this goal.’ He carefully pursued his studies step by step. First, a two-year university degree in bioengineering at Angers. ‘My studies were divided into professional phases, each step allowing me to find a job if I didn’t want to study anymore.’ The next step, in 2004, was in Lille for a master's degree in genomics and proteomics. This is where research hooked him. From 2008 to 2012, within unit U908 of INSERM (National Institute of Health and Medical Research), he completed a PhD thesis on breast cancer.


But like any young researcher, Mr Corbet knew that if he wanted to continue, a research experience abroad was necessary. For family reasons, he didn’t want to go too far, so the US was out. ‘I focused on Britain and Belgium’, he recalls. Enter chance. Prof. Olivier Feron (UCLouvain Pharmacology and Therapeutics Centre, FATH) was preparing to advertise a job offer for a postdoctorate when he received Mr Corbet’s application. The latter's research project interested Prof. Feron, who asked the young researcher to come and explain it in his laboratory. The job offer was never advertised. A postdoctoral fellow from 2012 to 2016, he became an FNRS postdoctoral researcher in 2016; in early 2019, he received the much sought-after Galien Prize for Pharmacology, then was named FNRS research associate – ‘condemned’ to Belgium, which he doesn’t seem to regret. ‘On the contrary,’ he smiled, ‘now that I have a fixed job, I’ll be thinking of living in Belgium. But above all, the research associate appointment will allow me to develop research themes in a more independent way even if it’ll of course always be tied to Prof. Feron’s laboratory. I think that's what all researchers aspire to.’


Cells that cease responding to treatment

What will be his research project in the coming years? Understanding why certain colorectal cancer tumour cells don’t or cease to respond to targeted treatments – which, according to models, they should nevertheless do.


Two words of explanation. UCLouvain's Pharmacology Laboratory studies metabolism, i.e. how cells feed. Cells use sugar, lipids and amino acids to produce the energy they need to divide, move, and produce the essential building blocks during their division for membranes, DNA, etc. The general idea is to cut these metabolic pathways in order to deprive the cells of the possibility of producing either the energy or the buildings blocks for multiplication. Specifically, the metabolism of cells located in very specific tumour areas, at the origin of treatment resistance, is targeted. ‘This is at least the hypothesis that I formulated’, Mr Corbet says.


The treatment in question here is not chemotherapy or radiotherapy, which are heavy treatments applicable to all cancer cases, but individual treatments that complement the former and are prescribed after genetic screening. ‘These are targeted therapies’, Mr Corbet says. ‘When a patient arrives in the clinic, they do a genetic test to see if there are mutations in the DNA. These mutations will guide the choice of treatment.’ An example: injecting an inhibitor of the metabolic pathway that controls cell division and thus inhibit the proliferation of tumour cells.


In colorectal cancer, 20% of patients experience nonresponse to specific treatments (or relapse). ‘I’d like to highlight the presence of highly resistant cells within the tumour cell cluster, in areas that make them very aggressive and hence resistant to treatment. We’ll kill 80% of cells but we’ll also select the remaining 20% which, in the absence of the others, will be able to divide and spread everywhere.’

Mr Corbet will now begin a longer race ... in search of funding. This half-marathoner isn’t discouraged. ‘Even as a postdoc researcher, the side tasks were already taking time. They’ll increase but that’s part of career development.’ Spoken without resignation, rather with the eagerness of a runner in the starting blocks.


Henri Dupuis

Published on October 01, 2019