Pisano C et al. - In a study to extend preclinical evaluation of ST1968 in human squamous cell carcinoma (SCC) models, it was shown that ST1968 exhibited an outstanding antitumour activity superior to that of irinotecan against SCC. A high intracellular accumulation, resulting in fast apoptosis or DNA damage persistence, appeared to be a critical determinant of SCC sensitivity to ST1968 Methods
This study was designed to extend preclinical evaluation of the novel camptothecin in human squamous cell carcinoma (SCC) models
Results
ST1968 exhibited an impressive activity with a high cure rate in SCC models
ST1968 produced 100% of complete response without evidence of regrowth in tumours characterised by susceptibility to drug-induced apoptosis (FaDu, A431 and A2780)
In contrast to irinotecan, ST1968 still showed an excellent, persisting activity in models less susceptible to apoptosis induction (KB, Caski and SiHa), in which drug treatment elicited a persistent DNA damage response, as documented by phosphorylation of p53, RPA-2 and histone H2AX, resulting in delayed apoptosis and senescence
This behaviour was associated with a marked cellular/tumour drug accumulation
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