Neoadjuvant clinical trials provide a window of opportunity for cancer drug discovery

Abstract

Window-of-opportunity trials, during which patients receive short-duration pre-surgical therapies, provide a platform for understanding the therapies’ mechanisms of action, but will require a paradigm shift in trial design, specimen collection and analysis.

Fig. 1 |. A paradigm shift in clinical trials.

Large teams of physicians and scientists must collaborate to rapidly learn from trials, and inform subsequent trials, in order to optimize the learning potential that window trials provide.

Fig. 2 |. Iterative-design trials enable and inform rapid informative trials.

An in-depth analysis of treatment-naive tumors can characterize the dysregulation that limits the immune recognition and elimination of tumors; identify optimal models to study this dysregulation; model therapeutic interventions in preclinical models; and bring this understanding back to the clinic.

Fig. 3 |. Communication and collaboration across medical silos.

Immune dysregulation is at the heart of much of human pathology, and the repurposing of biologic therapies capable of disrupting the immunological milieu has potential applicability across many disease states that are the focus of disparate groups of physicians. Through the study of immunological programs in pathological conditions across disease states, and collaboration across silos, established biologic agents used in one setting may enable clinical advances in another. As an example, TNF blockade was initially developed in rheumatoid arthritis, and only a decade later became a standard therapy for inflammatory bowel disease (IBD); and IL-1 blockade, initially promising for inflammatory conditions, was later found to be effective in preventing cardiovascular disease and potentially cancer.