Assays and screens

An assay utilizing drug-loaded, barcoded liposomes could help predict patient response to cancer therapies. The method involves loading 100-nM liposomes with subtherapeutic doses of a drug, tagging each liposome with a DNA barcode indicating its drug content, injecting the liposomes in vivo, then taking a biopsy from the tumor 48 hours post-injection. In a biopsy sample, live and dead cells were separated and lysed, and their DNA barcodes amplified and quantified to indicate the concentration of a drug within the cells. For each drug tested, a potency parameter representative of its predicted therapeutic efficacy was calculated from the ratio of its barcode count in dead cells to that in live cells. In a xenograft mouse model of triple-negative breast cancer (TNBC) injected with of a cocktail of liposomes loaded with doxorubicin, cisplatin, Gemzar gemcitabine or vehicle, the method yielded the highest potency parameter for Gemzar. Also in the mouse model, Gemzar decreased tumor growth and the fraction of mitotic cells in tumors compared with doxorubicin or cisplatin. Next steps included developing the method for clinical use.

Eli Lilly and Co. markets the nucleoside analog Gemzar to treat non-small cell lung cancer (NSCLC) and breast, ovarian and pancreatic cancers...