Insights from the Study of Exceptional Responders

There is enormous diversity in clinical response of cancer patients to anti-cancer drugs.  For many drugs, the vast majority of patients fail to respond, and yet some patients have extraordinary responses—unexpected exquisite sensitivity or unusually long durations of response to anti-cancer agents. Unfortunately, the molecular basis of these extraordinary responses is often unknown—as a result we lack the ability to predict who will benefit from these therapies and who will not.  This leads either to drugs being declared not effective and abandoned, or to large numbers of patients being treated with drugs to which they will derive toxicity but no benefit. In this presentation, we will discuss how studies of patients with extraordinary responses to therapies can lead to insights that can help develop methods for optimally matching patients to drugs, highlight effective uses for otherwise “failed” therapies, and aid with future development of anti-cancer therapies. We will also discuss how genomic studies of small numbers of patients can have clinical implications for many more patients.  Finally, we will discuss novel methods for identifying and characterizing patients with extraordinary responses, and the translation from extraordinary responses to precision medicine approaches through prospective genomic profiling, basket trials, and complementary functional experimental approaches.