We use the term "systems pharmacology" to define research that aims at understanding how drugs work (on specific pathways, on different cell types and in different tissues/organs/diseases), what the variability in patient response is and why many cancer treatments fail. Using a broad array of technologies including in vivo imaging of pharmacokinetics, intravital pharmacodynamic imaging (IPDI), mass spectrometry analysis, novel nanotechnology sensing approaches and chemical biology we obtain quantitative measurements and then develop mechanistic and probabilistic models. Network analysis and quantitative measurements of drug actions and side effects play a key component. Ultimately, we hope to improve our poor understanding of treatment response and define new targets drugs (or synergistic combinations) to tackle complex diseases.
Some of the Questions we are currently addressing are:
- What are the molecular and cellular pathways from drug engaging target to tumor regression for any drug ?
- What makes a cancer cell more, or less, responsive to drug X than a cell in the most relevant normal tissue (where toxicity occurs) ?
- Why do some patients respond better than others? How can we predict the best drug/combination for a particular patient ?
- How do cancers become drug resistant, and how can we combat this ?
- What is the effect of cancer drugs on immune cells and can drug combinations be used to enhance anti-cancer efficacy ?
- What are the most appropriate read-outs of drug efficacy and toxicity in clinical trials ?
- How does taxol work on cancers if only < 5% of cancer cells are in M-phase in vivo ?
This Program is multidisciplinary and inter-institutional involving investigators from the Department of Systems Biology at Harvard Medical School (Initiative in Systems Pharmacology), Harvard affiliated teaching hospitals and MIT.