The birth of cancers - a route to prevention

A Lola and John Grace Distinguished Lecture in Cancer Research
This seminar will also be televised to CHUV/AGORA, Biopôle and Geneva University (rooms tbc)

 
Cancers are distributed unevenly in time and space: malignancies occur with predictable incidence in each organ system, and despite enormous mitotic and differentiation stress, cancers are rare in multi-organ species during development.  The relative importance of cell intrinsic and extrinsic factors in determining the topographical and temporal distribution of cancer risk is unknown. In published and ongoing work we have used Cre-recombination of conditional lineage tracing, oncogene, and tumour suppressor alleles to define populations of stem and non-stem cells in mouse organs and test their life-long susceptibility to tumorigenesis. We show that tumours arise solely within cells harbouring stem cell function, and that neonatal stem cells are intrinsically resistant to cancer. This relationship held true in the presence of multiple genotypes across all organs, strongly supporting the notion that stem cells dictate organ cancer risk. Using organ damage models, we further show that damage-induced activation of stem cell function markedly increases cancer risk. Finally, in a large ongoing mapping study we are charting the transcriptome, proteome and methylome of stem cell populations across twelve organs at multiple developmental time points from embryogenesis to old age. We propose that a combination of stem cell mutagenesis and extrinsic factors that enhance the proliferation of these cell populations, creates a "perfect storm" that ultimately determines organ cancer risk. Furthermore, understanding the mechanism(s) by which neonatal stem cells resist cancer might unmask novel cancer prevention strategies.