Exceptional Responders: Exploring the Molecular “Make-up” of Patients with Cancer Who Experienced Recovery

Patients with cancer, who have achieved an unexpectedly favorable and long-term clinical response are commonly known as exceptional responders (ER). Such patients have often experienced extraordinary responses to some oncology therapies, which have been ineffective for other individuals with similar malignancies. These unusually positive responses may be partially due to some unique genetic and molecular mechanisms, which can be further studied. This, in turn, could provide some directions to a better understanding of why the specific therapy works for only a small number of patients with cancer, but not for everybody. To further elucidate these issues, the National Cancer Institute (NCI) has been conducting various research projects to explain biological processes, which can be responsible for these remarkable responses. A recent pilot study, known as the Exceptional Responders Initiative (ERI), has evaluated the feasibility of identifying exceptional responders retrospectively, by obtaining pre-exceptional response treatment tumor tissues and analyzing them with modern molecular tools. The promising findings of this study can inspire many women with breast cancer (BC) and their medical teams. This chapter presents a synopsis of the ERI. It suggests some possibilities to adjust this concept for patients with breast cancer (BC) (e.g., advanced or metastatic triplenegative breast cancer (TNBC)). 

Keywords: Actionable mutations, Exceptional responders, Exceptional responses, Integrated studies, Next-generation sequencing (NGS), Precision oncology.