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[Plenary] Himisha Beltran: Lineage plasticity and the neuroendocrine phenotype in prostate cancer

Himisha Beltran
Dana-Farber Cancer Institute, MA, USA


Lineage plasticity has emerged as an important mechanism of treatment resistance in prostate cancer. This is associated with loss of luminal prostate markers, and in many cases induction of developmental programs, stem cell-like phenotypes, and neuroendocrine/neuronal features. Clinically, lineage plasticity may manifest as low prostate specific antigen (PSA) progression, resistance to androgen receptor (AR) pathway inhibitors, and sometimes small cell/neuroendocrine pathologic features observed on metastatic biopsy. This mechanism is not restricted to prostate cancer as other malignancies also demonstrate lineage plasticity during resistance to targeted therapies. At present, there is no established therapeutic approach for patients with advanced prostate cancer developing lineage plasticity or small cell neuroendocrine prostate cancer (NEPC) due to knowledge gaps in the underlying biology, few clinical trials address questions in this space, and the outlook for patients remains poor.  We will discuss recent updates on our understanding of how lineage plasticity occurs, emerging mechanisms, and clinical/therapeutic implications.


Dr. Beltran is a medical oncologist and physician scientist focused on understanding mechanisms of treatment resistance in advanced prostate cancer. Her lab has developed therapeutic targets and biomarkers for non-AR driven prostate cancer including neuroendocrine prostate cancer, an aggressive subtype of castration resistant prostate cancer. As recent Director of Clinical and Translational Research within the Weill Cornell Institute for Precision Medicine and now as Director of Translational Research in Medical Oncology at Dana-Farber Cancer Institute, she works to develop molecularly based treatment approaches for patients including through the establishment of protocols for metastatic biospecimen collection, serial blood collection, and the use of next generation molecular assays. She has led the development and characterization of patient-derived tumor models including prostate cancer organoids and patient-derived xenograft (PDXs).  Her lab uses these models to understand mechanisms of treatment resistance, with a particular focus on lineage plasticity and neuroendocrine prostate cancer.  Dr. Beltran has authored over 100 publications and plays an active role in national  and international committees as well as team science projects, helping to integrate multiple disciplines in order to accelerate prostate cancer translational research including within the Prostate Cancer SPORE Program and the International Stand Up to Cancer (SU2C)-Prostate Cancer Foundation (PCF) Dream Team.


Host: Alvaro Aytes