ATYPICAL RESPONDERS LANDSCAPE REVIEW ∙ OCTOBER, 2017 7 RESEARCH AND ANALYSIS INITIATIVES THAT ARE INVESTIGATING AN “ATYPICAL RESPONSE” AND ASSOCIATED DESCRIPTIONS Atypical responders encompass groups of patients at either end of the therapeutic spectrum: those who respond to a given therapy either remarkably well or remarkably poorly. In the absence of standard categories, several groups have incorporated a working framework for “exceptional responders” into published or ongoing studies (Table 1, p.31). Multiple research initiatives are underway in the US and abroad to identify the reasons why some cancer patients respond extraordinarily well to a particular therapy and others do not. Nearly all of these initiatives are studying molecular aberrations associated with patients’ tumors in an effort to understand the role these anomalies play in the therapeutic response, and most of them focus solely on exceptional responders. These studies are observational registries and not interventional trials. A list of these studies is provided in Table 2 (p. 33). We suggest that clear categorization of atypical responses is needed, and that atypical responses may be due to multiple factors including: • tumor genomics • normal tissue genomics • the environment in which the tumor is located • co-morbidities and the drugs taken for them • lifestyle factors • practice of complementary and integrative medicine (CIM) • factors that determine chemosensitivity and chemoresistance