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Hypoxia and blood flow heterogeneities are characteristics of solid tumours and are major obstacles for therapy. Exploiting the biology of nitric oxide (NO), a small radical with multiple functions, is particularly attractive to circumvent these sources of resistance and to sensitise tumour to cytotoxic treatments such as radiotherapy and chemotherapy. Indeed, while NO mediates angiogenic effects, NO may also promote tumour perfusion, drug delivery and oxygenation. Different strategies to deliver NO to tumours and pertaining to the FECS-EJC award laureate's work are reviewed, with a focus on their therapeutic potential. The development of techniques to monitor how and to which extent NO delivery influences the phenotype of a given tumour in a given patient is also discussed.

observed decreased p16. Detailed analysis showed that HLX1 affects INK4a expression at the mRNA level and HLX1 binds to the INK4a promoter as observed by ChIP. We also observed increased levels of the repressive H3K27me3 mark and recruitment of PRC2 components at the Ink4a/Arf locus correlating with HLX1 expression. Co-immunoprecipitation studies showed that HLX1 associates with the PRC2, in particular with Suz12. RNAi studies showed that the repression of p16 by HLX1 is dependent of PRCs. In an attempt to understand if the repression of HLX1 was a property shared by other homeobox genes, we tested 20 homeoboxcontaining genes and identified that multiple homeobox can also repress p16. Conclusions: We identified the homeobox protein HLX1 as a novel p16 repressor. HLX1 binds to the INK4a promoter region and recruits Polycomb repressive complexes. Multiple homeobox proteins can also regulate p16 expression, which implies a conserved role for this family oftranscription factors in regulating the Ink4a/Arf locus, highlighting its potential physiological relevance for both senescence and carcinogenesis.