3rd EurocanPlatform Translational Research Course

From genotype to molecular phenotype by proteomics

Dr Janne Lehtiö - Karolinska Institutet, Stockholm, Sweden

I would say the main message is that cancer proteomics is really entering the big time, the cancer research field. The methods have developed a lot in the past only a few years. We have published draft maps of the human proteome now out there and there is virtually in all the issues of high impact cancer journals and other journals proteomics data. So you should get interested in proteomics and look what’s going on the field; it’s looking at the molecular phenotype. So I guess that one of the main messages is that all of the genomic aberrations and transcriptomics events are converted to effects at the protein level and if we connect that to the cancer genome effect we can understand better the connection between the genotype and molecular phenotype.

What significance does this have for clinical practice?

I think that one of the big issues is how do we combine the current cancer treatments. We are actually developing a large number of drugs that are hitting protein targets. So we should look at the proteins and the protein signalling. So if we couple that information by doing proteomics, phosphoproteomics, other types of proteomics, we can be better to understand how to treat the cancer and how to combine the targeted therapies.

What are the next steps?

I would say that the next step is to actually move it to analyse in the large clinical materials, first retrospective cohorts and run proteomics and different types of protein level analysis on the large cohorts and then convert that into a sort of routine analysis by, first, in a research setting to take samples and analyse them, analyse the proteome of the samples in a day to day basis, and when we gain information and knowledge how we can use that then I think we should add that as an omics measurement in the clinical setting.

What will the eventual benefit be of this work?

The benefit is that we will understand how to treat cancer and how to combine the targeted drugs in a patient benefit. We will also be able to convert the protein level measurements into biomarkers, monitoring biomarkers, predictive biomarkers and eventually when the methods get more sensitive to early detection markers.

What would be your take home message?

You should really get interested to look at the proteome right now. Methods have developed and matured and we can definitely start analysing large clinical materials. If you are planning to do genomics and transcriptomics you should talk to your proteomics collaborator or find one and do proteomics as well.