The landscape of rare cancer : a sea of opportunity Boyd, Niki; Dancey, Janet E.; Gilks, C. Blake; Huntsman, David G.
Rare cancers, as a collective, account for approximately one-quarter of all cancer diagnoses and deaths. Historically, they have been divided into two groups. The first was defined by their unusual histogenesis (cell of origin or differentiation state), and include chordomas or adult granulosa cell tumours (aGCT). Most tumour types from this first group are still clinically and biologically relevant and have been disproportionally important as sources of insight into cancer biology. The second grouping of rare cancers were histologically defined subtypes of common cancers, most of which have been shown to have neither defining molecular features, nor clinical utility. ‘Omics based analyses has splintered common cancers into a myriad of molecularly rather than histologically, defined subsets of common cancers, many of which have immediate clinical relevance. Today, almost all rare cancers are either histomolecular entities, which often have pathognomonic mutations, or molecularly defined subsets of more common cancers. The presence of specific genetic variants provides rationale for testing targeted agents in rare cancers, however, the essential contributions of both mutation and cell context in the development, biology, and behaviour of these cancers suggest that designing trials of drugs based on the presence of mutations, without consideration of cellular context (the specific genomic and signalling architecture in which mutations operate) is naïve. Patients with rare cancers are disadvantaged due to challenges of participating in clinical trials however, the number of patients with rare cancers will only increase as more molecular subsets of common cancers are identified, and as this happens, it will be necessary to shift the focus of clinical trials and research to cancer types, which by epidemiological definitions are rare tumours.
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