Targeted Therapy in Neuroendocrine Cancer

Division Of Basic Sciences - Nci

Investigators

Linked publications & trials

Abstract

Our prior work at the NCI led to the FDA approval of a PET-imaging agent, Ga-68 DOTATATE, targeting the surface receptor type 2, that not only help identify them as neuroendocrine tumors, but also represent key pro-growth and pro-survival pathways. In aggressive or metastatic neuroendocrine tumors, that are not amenable to surgical resection, a novel radiolabeled SSTR2 analogs for the therapy of metastatic lesions (Lu177-DOTATATE) has been used. Unfortunately, with dedifferentiation, the tumors lose SSTR2 expression, and renders them invisible or not amenable for targeted therapy. OUr research has defined the epigenetic regulation of SSTR2 surface expression and we validated the upregulation of SSTR2 using HDAC inhibitors. THis led to a successful Lasker award submission. We are continuing our efforts to translation into a clinical trial and are awaiting CTEP and industry approval. Furthermore, with collaborations, we have expanded we have expanded our research to involve elucidating the genetic and epigenetic drivers of tumor progression, in order to better define patient tumors with aggressive behavior. This is done by performing multiome (single cell RNA and ATAC) sequencing on our cryopreserved fresh human surgical tumor samples. The analysis involves defining transcription factors involved in tumor progression within matched primary-liver metastases samples.