Organoid models
A major hurdle in the study of advanced prostate cancer and resistance mechanisms is a lack of existing preclinical models. Our lab has generated and characterized tumor organoids derived from needle biopsies of metastatic lesions. We have demonstrated concordance of molecular features between organoids and their corresponding patient tumors. These organoids also develop metastatic disease when transplanted into animals as xenografts. We are utilizing these organoids and organoid xenografts to understand the biologic role of epigenetic modifiers and other emerging drivers of NEPC progression and metastasis. High-throughput organoid drug screening nominated single agents and drug combinations suggesting repurposing opportunities (Puca L et al). |
Liquid Biopsies
Serial biopsies to look for NEPC transformation or other mechanisms of treatment resistance are not always feasible or safe for patients with advanced prostate cancer. We are developing liquid biopsy approaches including circulating tumor cells and circulating tumor DNA (genomics and methylation) to detect the emergence of resistance features non-invasively (Beltran et al; Franceschini et al). |
Precision Medicine
Genomic profiling is widely used in cancer care to identify actionable alterations for individual patients within the context of precision medicine (Mateo et al; Ku et al). However, not all patients with sequencing performed receive a targeted therapy, due in part to accessibility to clinical trials as well as a still incomplete understanding regarding the clinical, biologic and functional impact of identified alterations. We are working across cancer types to interrogate the genetic and molecular landscape of cancer, including the integration of newer platforms, such as whole genome sequencing, RNA-seq, and DNA methylation, to understand the functional and clinical significance of both common and uncommon molecular alterations and to develop new and informed therapeutic approaches for patients. Through collaboration within a multidisciplinary team at DFCI spanning both the clinic and the lab, we are working to develop the next generation of biomarkers and targets to inform cancer care. |