We aim to determine the molecular features that associate with response and resistance mechanisms to pathway-targeted agents and conventional chemotherapy. Several clinical (translational) trials are underway including studies incorporating neoadjuvant therapies and large-scale tumor genome sequencing. Tissue samples are acquired pre- and post-therapy and molecular correlates of direct drug effects are identified to define tumor and host signatures: (a) predictive of therapeutic response and (b) predictive of disease outcome (relapse). We are also exploring new minimally-invasive approaches to assess the molecular composition of tumors using circulating tumor cells (CTCs) and cell-free tumor DNA (ctDNA) biomarkers that allow for iterative sampling of tumor biology and direct therapy.
A major focus involves the identification of synergistic drug combinations. For most solid tumors, single drugs fail to completely eradicate metastatic cancers and resistance is universal. Through collaborative studies, we are employing unique panels of patient-derived xenografts (PDX) and organoid models to identify rational drug combinations capable of producing complete responses.