Researchers at Dana-Farber Cancer Institute and the University of Trento have developed a blood test that can reliably detect NEPC and differentiate it from CRPC-adenocarcinoma – Dana-Farber Cancer Institute
Dana-Farber Cancer Institute shared a post on LinkedIn:
“Like a criminal entering a witness protection program, cancer cells can shed their past and take on a new identity. Detecting such an identity-switch is particularly challenging when metastatic castration-resistant prostate cancer (CRPC) advances from adenocarcinoma to neuroendocrine prostate cancer (NEPC), a very difficult cancer to treat. Now, however, researchers at Dana-Farber Cancer Institute and the University of Trento, Italy, have developed a blood test, described in Cancer Discovery, that can reliably detect NEPC and differentiate it from CRPC-adenocarcinoma (CRPC-adeno).
NEPC is currently diagnosed using a biopsy of tumor tissue from a metastatic tumor site. Yet, it isn’t always clear to clinicians when to do a biopsy. Further, biopsies may be unreliable since metastatic tumors are often heterogeneous.
‘As prostate cancer treatments get more effective, we expect the emergence of different types of treatment resistance like neuroendocrine prostate cancer that help them evade treatment,’ says co-lead author Himisha Beltran, associate professor of medicine, Lank Center for Genitourinary Oncology and the Division of Molecular and Cellular Oncology, Dana-Farber Cancer Institute. ‘We hope this blood test can be used by clinicians to determine if a patient is developing neuroendocrine prostate cancer.’
Approximately 10-15% of patients with metastatic prostate cancer develop NEPC. The transition involves a shift from cancer cells that are dependent on hormones called androgens to cancer cells that no longer even recognize androgens. ‘They can stop expressing the androgen receptor,’ says Beltran. ‘They shut down their hormone-driven identity and they turn on a new identity as a way to develop resistance to treatment.’
In previous research, the international team studied tissue samples from biopsies to identify the genetic and epigenetic changes related to this transition. They found that, across the whole genome, specific epigenetic changes, in the form of DNA methylation changes that switch genes on or off, distinguish CRPC-adeno from NEPC.
These epigenetic changes can be detected in blood because the body is constantly shedding fragments of dead cells into the bloodstream. Those cells come from all over the body, including from tumors. The fragments include bits of DNA, called cell free DNA (cfDNA), along with whatever epigenetic tags and structures were attached to them when the cell died.
Beltran collaborated with a computational team at the University of Trento, led by Francesca Demichelis, PhD, co-lead author on the study, to create a blood panel test, called NEMO (NEuroendocrine MOnitoring panel). “The test selectively probes cfDNA in blood plasma for relevant DNA fragments and measures their methylation,” says Demichelis. “Because the number of methylated regions needed to distinguish between normal, CRPC-adeno, and NEPC cells is small, the panel of genes sequenced by the test is minimal and efficient.”
