Tissue-based predictive biomarkers

Aart Mookhoek, H-ECCO Committee Chair

Aart Mookhoek

The last decade has seen a dramatic increase in drugs available for the treatment of IBD. However, each of these novel biologics or small molecules achieves disease remission in only a relatively small proportion of patients [1].To date, implementation in clinical practice of evidence that assists in better evaluating the chance of therapy success in a particular patient for a particular drug is limited. Therefore, when choosing a drug for a patient with IBD who is starting therapy or needs to switch drugs, a trial-and-error approach may be unavoidable.

To address this unmet clinical need, several research groups have now turned their attention to biomarker discovery to allow development of an evidence-based personalised treatment strategy [2]. At this year’s Congress of ECCO in Stockholm, I had the opportunity to provide an update on the field of biomarker discovery from the perspective of a pathologist. In this issue of ECCO News, I want  to share with you the most important points from that H-ECCO Masterclass talk.

Although the sources of potential biomarkers are many, I will limit my overview to tissue-based biomarkers. This choice is driven by the hypothesis that directly studying the complex interactions between the microbiome and the innate and adaptive immune system is key to biomarker discovery in IBD.

Biomarkers have been reported in different omics layers. As a pathologist, my interest, however, is first drawn to observations in H&E-stained slides. Several studies have shown that eosinophils in the lamina propria have a predictive value. However, whereas one study has reported a high eosinophil number in association with therapy response [3], another has reported the opposite [4].Assessment of the proteome reveals a similar problem when studying the level of α4β7+ mucosal immune cells [5, 6]. In transcriptomics, the now publicly available dataset from the GEMINI II trial on vedolizumab has led different groups to publish marker sets with marked heterogeneity regarding marker number and with limited marker overlap between studies.

The above examples illustrate why implementation of biomarkers in clinical practice is problematic. Several problems in the field were already highlighted in an ECCO publication on precision medicine [7]. One major problem is the heterogeneity regarding how (clinically, endoscopically or histologically) and when therapy response is measured. Moreover, only a handful of studies have validated their biomarker or set of markers.

The ECCO Community is the perfect platform to reshape the field and work towards a future of biomarker-driven treatment strategies.

Posted in ECCO News, Committee News, Volume 19, Issue 2, H-ECCO