Metformin, a widely used anti-hyperglycemic drug in the biguanide class, is currently under investigation for
the prevention of cancer. Surprisingly however, considering the time and cost of clinical chemoprevention trials and the
current scrutiny of cancer chemoprevention, limited attention has been given to integrating available data, identifying the
subpopulations most likely to benefit, or to quantitatively understanding the potential pitfalls of biguanide chemoprevention.
Herein, a physiologically-based pharmacokinetic (PBPK) and pharmacodynamic framework is proposed for integrating
information on physicochemical, cell-based, animal, and human studies of various biguanides to identify gaps in
knowledge and to build a systems model that may facilitate the planning of randomized cancer chemoprevention trials of