Unveiling the molecular pathogenesis of chordoma: a new paradigm for molecular targeting of rare cancers
'Chordoma' represents orphan sarcoma subtypes in which systemic treatments have so far proved ineffective. Two original papers in the Journal of Pathology have recently elucidated important steps of its molecular oncogenesis. The demonstration of gains of copy number of both T (brachyury homologue) and EGFR (epidermal growth factor receptor) genes in chordoma, as well as of their role in promoting cell proliferation, offers a strong preclinical rationale for exploring the inhibition of their products as a credible therapeutic strategy. When dealing with rare cancers, clinical trials based on a frequency-based statistical methodology are hardly feasible. To override the limitations of rarity, the clinical community is suggesting the adoption of a Bayesian methodology. The success of innovative clinical trials strongly depends upon the availability of preclinical evidences of efficacy. The papers discussed herein represent good examples of what is actually needed to set up a solid prior probability.