Unveiling heterogeneity: the pressing challenge to cancer diagnosis and therapy

Since the pioneering studies of Heppner and co-workers on mouse mammary cancer, the presence of heterogeneous phenotypes and genotypes within the cancer bulk has been clearly demonstrated in several types of malignancies. Different co-existing sub-populations, arising from both genetic and non-genetic variability and providing both heritable and non-heritable clones, give rise to an organized community in which not only cooperative but also conflicting interactions may set up. The resulting clonal crosstalk guarantees tumour growth, helping its spread through metastasis and the emergence of resistance to the commonly exploited anti-cancer treatments. Although aware of tumour heterogeneity, we are still far from understanding how different phenotypes and genotypes interact, thus allowing the whole community to survive therapeutic selection and/or suppression. This is why we failed so far to fine-tune a long-lasting, effective treatment for this kind of pathology. Accordingly, untangle tumour complexity is a basic and urgent challenge scientists should not work around anymore.