YM155 is a novel small molecule compound which inhibits survivin, a member of the inhibitor of the apoptosis protein family. According to the recent paper published in British Journal of Cancer (June 1), 2010 YM155 sensitises tumour cells to platinum compounds both in vitro and in vivo.

The researchers explain that this effect is likely attributable to the inhibition of DNA repair and consequent enhancement of apoptosis.

YM155 specifically inhibits the expression of survivin at both the mRNA and protein levels and exhibits pronounced anti-cancer activity in pre-clinical models. Also, the researchers have recently shown that YM155 sensitised Non Small Cell Lung Cancer (NSCLC) cells to radiation both in vitro and in vivo. But its combination with DNA damaging drugs (cisplatin, carboplatin) has largely been unknown. "Our study tries to explore this combination in vivo and in vitro" the authors noted.

The anti-cancer efficacy of YM155 in combination with platinum compounds was evaluated on the basis of cell death and progression of tumour xenografts. Platinum compound-induced DNA damage was evaluated by immunofluorescence analysis.

Immunofluorescence study revealed YM155 compound delayed the repair of double-strand breaks induced in nuclear DNA by platinum compounds. With this combination number of apoptotic cells was found to have increased. Likewise, combination therapy with YM155 and platinum compounds delayed the growth of NSCLC tumour xenografts in mice to an extent greater than that apparent with either treatment modality alone.

About the implication of their study the authors explain "Platinum-based combination chemotherapy is the standard of care for most individuals with advanced NSCLC. We have shown that treatment of NSCLC cells with YM155 results in a marked increase in the anti-tumour effects of cisplatin and carboplatin both in vitro and in vivo, suggesting that the combination of YM155 and platinum compounds may have potential as a novel therapeutic regimen".