Dr. Himisha Beltran, an Assistant Professor of Medicine at Weill Cornell Medical College in New York City, is keenly interested in developing research programs to study neuroendocrine prostate cancer.
We spoke with her about this aggressive form of prostate cancer.
Your research deals with a small subset of patients and is considered a specialized area of research. How did you become interested in neuroendocrine prostate cancer as opposed to another aspect of the disease?
Dr. Himisha Beltran: I take care of prostate cancer patients at all different stages of their disease. We know that not all patients with prostate cancer are the same and they may respond variably to the therapies that we use. My research has focused on understanding mechanisms of treatment resistance and identifying subsets of patients that may benefit from nonstandard approaches.
Neuroendocrine prostate cancer is one subtype within the spectrum of advanced prostate cancer that tends to look and act differently compared to your typical prostate cancer. They tend to be less responsive to standard therapies and often do not make PSA.
That is really what led me to neuroendocrine prostate cancers. I was struck by how some patients had tumors that looked very different under a microscope and acted very different clinically than others looked and acted. By understanding a small subgroup of patients, we can also better understand the entire group. That is really what precision medicine is about: identifying subgroups of patients that either have clinical, molecular, or other features that will help guide treatment. While my research is focused on a small subgroup of men, I think the impact potentially affects many more.
Let’s back up a bit and define neuroendocrine prostate cancer.
Dr. Beltran: Most prostate cancers consist of adenocarcinoma cells, which are derived from normal prostate tissue. They have more glandular prostate features. They express many prostate markers. When we say a cancer is neuroendocrine, we mean that the tumor looks less like a typical adenocarcinoma and has features that look more like neuroendocrine cells, which have a distinctive morphology under a microscope. Neuroendocrine cells tend to be smaller and may not express classical prostate markers such as the androgen receptor, which is the target of many of our drugs like Zytiga (abiraterone) and Xtandi (enzalutamide). These cancers also acquire other distinct molecular features.
What we’ve learned in recent years is that neuroendocrine prostate cancer rarely arises de novo; they most commonly develop in later stages of prostate cancer progression from a preexisting prostate adenocarcinoma as a way for the cancer cells to evade therapy. The tumors try to change their identity to develop new ways to grow. There is a spectrum as tumors progress from androgen-driven prostate adenocarcinoma toward an androgen independent neuroendocrine prostate cancer. Within this spectrum, the cancers may develop mixed or overlapping features, expressing some prostate markers but also acquiring new resistance markers.
Is there any way to predict who is going to develop treatment resistance?
Dr. Beltran: By studying the clinical and molecular features of patients, how cancers evolve with time, and how these features affect the biology of the cancer, we now have better insights into mechanisms of response and resistance to specific therapies. This growing knowledge sets the stage for biomarker development.
We are interested in identifying patients before they develop neuroendocrine prostate cancer. We are investigating the genomics and other molecular features of tumor biopsies and applying this to noninvasive approaches such as liquid biopsies— looking at cancer cells or DNA from cancers that may be detected in the blood. If we can identify patients, we can also select patients most likely to benefit from a neuroendocrine type of regimen.