Clinical approach and utilizing liquid biopsies to interrogate suspected acquired resistance to PD-1 blockade

PD-1 blockade is now routine for nearly all patients with non-small lung cancer. Acquired resistance to PD-1 blockade – defined generally as an initial response followed later by progression [ 1–3 ] is a common yet poorly understood concept. A key clinical challenge to insight has been a lack of standard guidance for clinical management of a case of suspected acquired resistance. The infrequency of performing tumor biopsies and the uncertainty of actionability from tissue sampling likely also contribute to limited insight into the biology of acquired resistance [ 4 ]. To address this knowledge gap and to highlight the value of tumor and liquid biopsy, we present a representative case of suspected acquired resistance to PD-1 blockade and propose a multi-modal guide for approaching this clinical scenario.