According to a report by the Spanish Society of Medical Oncology (SEOM), colorectal cancer is the cancer with the highest incidence rate (15%) in both sexes in Spain. This datum, together with its high mortality rate after five years (it is the second most worrying tumour, surpassed only by lung cancer), obliges the scientific community to step up its efforts to obtain better diagnostic methods and treatments for this oncological disease.
It is precisely the big data analysis that has generated one of the most important recent breakthroughs in the treatment of colorectal cancer. An international consortium, led by the Oncology Data Science Group of the Vall d’Hebrón Instituto de Oncología (VHIO), has published the first international and ground-breaking consensus in the genomic classification of this type of tumours in Nature Medicine.
After studying 4000 patient samples, the team managed to determine four distinguishable subtypes depending on their molecular characteristics. Thus, in Nature Medicine, the investigators assert that the six colorectal cancer classification systems that formerly existed may now be grouped together into the new consensus. This will allow us to leave all the past inconsistencies and uncertainties in clinical practice behind us, since colorectal tumours can respond very differently to the same treatment. This variability can now be explained by the biology of the different tumours, which, in the words of Dr Rodrigo Dienstmann, is "radically different".
Photograph of Dr Rodrigo Dienstmann. Source: Vall d’Hebrón Instituto de Oncología (VHIO)
The new “disease taxonomy” (as defined by the authors of the proposed classification), achieved through the big data analysis regarding tumour gene expression, also correlates this information to clinical behaviour and patient prognosis. The four subtypes (Consensus Molecular Subtypes, CMS) present a different incidence rate and traits: 14% were CMS1 (microsatellite instability immune), 37% were CMS2 (canonical epithelial, with activation of WNT, MYC and EGFR signalling), 13% were CMS3 (metabolic epithelial, of the metabolic pathways associated with mutations of the KRAS gene) and 23% were CMS4 (mesenchymal, with prominent activation of TGF–β, the presence of stromal invasion and angiogenesis). The remaining percentage (13% of the samples analysed) possibly correspond, according to the authors, to a transition phenotype or to the intratumoral heterogeneity observed.
The characteristics of the subtypes described by the international consensus have major clinical relevance. For example, the CMS1 is characterised by having great immune system activation, whereby immunotherapy would deliver greater benefits to patients in these cases. On the contrary, the CMS4 subtype has a very negative prognosis for conventional colorectal cancer therapies, as it is described with a prominent activation of the TGF–β pathways. Nevertheless, these initial deductions must be confirmed with clinical trials, which are already ongoing in organisations such as the VHIO itself, or the Catalan Institute of Oncology, in order to "study the clinical applicability of this classification”, says Dienstmann.
For these first conclusions to reach clinical practice quickly, the consortium has developed Open-Access-type biocomputing tools that will be used to classify colorectal tumours if microarray genetic data are available. The VHIO's joint work, which also featured the participation of SAGE Bionetworks of Seattle, will permit a paradigm shift in the approach to colorectal cancer, in a way similar to what has occurred with breast tumours in recent years. In the latter, the analysis of the patients' genetic big data resulted in a consensus-based classification that subsequently translated into personalised patient treatment. Scientific and clinical breakthroughs in breast cancer are largely responsible for the fact that this tumour now presents a mean relative survival rate of 89.2% after five years, according to the SEOM. Could something similar occur in the future with colorectal cancer?