Investigating resistance mechanisms to gemcitabine using a whole genome RNAi approach

There is a growing need to personalise anti-cancer treatments because cancers, like individuals, are somewhat unique. Although gemcitabine is the backbone of several cancer treatments, it is effective in only the minority of patients; major resistance mechanisms in cancer cells dramatically limit its activity. Hence, patients receiving this compound have only a marginally improved life-span, compared with untreated individuals. The novel molecule NUC-1031 is designed to overcome these cancer resistance mechanisms and benefit the majority of patients. The studentship will involve a comprehensive and unbiased search across all human genes, aiming to identify the specific ones associated with cancer resistance to gemcitabine treatment. This work will involve laboratory experiments using cell culture models of cancer and tools to reduce the expression of genes. Any candidate genes will be validated thoroughly to find any associated with drug resistance. This approach promises real benefit for patients, since identified genes can be used as biomarkers to select the appropriate treatment for the most suitable patients. By better understanding drug resistance pathways, personalised treatment with NUC-1031, which is in early clinical studies, can be planned systematically. Therefore, the results obtained will enable patient identification of those most likely to gain a superior response from the novel agent NUC-1031.