An adequate drug dose and sufficient exposure time are crucial for a drug to achieve its therapeutic effects. The dose must be high enough to ensure that the drug effectively binds to its disease-causing target, and sufficient time is required for the therapeutic effects to propagate through downstream signaling pathways. In cancer treatment, the primary therapeutic objective is to eradicate cancer cells, as illustrated in the figure to the right.
Most early drug development focuses on enhancing drug potency or dosage by optimizing drug-target affinity (Kd). This strategy proves highly effective in early drug-testing assays that involve purified proteins. However, in cell- and animal-based assays, translating target binding into a therapeutic response necessitates a specific timescale (tsig). Research suggests that this timescale is vital for accurately predicting response rates in animal models. The necessary “Threshold Concentration” (CT) to eradicate diseased cell populations depends on the dose, tsig, and the rate of cell proliferation. Conceptually, drugs that act more quickly within cells often require lower concentrations to achieve a therapeutic effect.
The Douglass laboratory develops new drug assays to better understand the dynamics of clinical drugs, specifically their therapeutic and toxic effects on disease cells and immune cells. We utilize real-time cell viability assays to monitor cancer growth and drug responses over time. As shown in the data to the right, the format of this data closely mirrors how drug responses are estimated in animal models and humans by tracking tumor size over time. Crucially, our assays are compatible with high-throughput screening robotics, allowing us to analyze the effects of approximately 2,000 drugs across 36 time points simultaneously. In the long term, these assays aim to assess the impacts of all known drugs on the cancer and immune cells of individual patients, identifying optimal treatments for cancer patients who have not responded to standard therapies.