Circulating Tumor Cells Associated With Brain Metastasis

A distinct group of circulating tumor cells (CTCs) associated with brain metastasis has been detected by Houston Methodist cancer researchers. The finding brings cancer researchers closer to understanding how the “seeds” of metastatic disease can thrive in breast cancer patients and cause it to spread to the brain.

Study leader Dario Marchetti, Ph.D, director of the Biomarker Research Program at Houston Methodist Research Institute, said:

“Our research confirmed that CTCs in breast cancer brain metastases are distinct from other circulating tumor cells. Moreover, unlocking the mystery of how these seeds of metastatic disease survive and thrive over a period of years, sometimes decades, is an enigma in cancer. Now we can take this information and develop a more sensitive screening tool to detect metastatic cancer in the blood, possibly even before metastasis is radiologically detectable by MRI.”

Magnetic resonance imaging is the accepted standard-of-care to diagnose breast cancer brain metastasis (BCBM) in patients. However, in most cases, by the time MRI detects the metastatic mass, the cancer has progressed to a stage where few curative treatment options are available, leading to poor overall survival.

Brain Metastatic Disease

According to extensive clinical studies, approximately 20 percent of breast cancer patients will develop brain metastasis over their lifetime, and, in general, metastatic disease to the brain is estimated to become the number one cancer killer within the next decade.

“Our lab is the first in this field to perform a comprehensive report of patient-derived circulating tumor cells at the gene expression level, so we now have a clearer picture of the signaling pathways that allows them to establish brain metastases. By comparing the whole genome expression patterns of CTCs isolated from patient blood samples diagnosed with or without BCBM, we uncovered a 126 gene-signature that is specific to these brain metastatic CTCs,”

said Debasish Boral, Ph.D, the paper’s first author and a research associate with the Biomarker Research Program at Houston Methodist Research Institute.

Circulating Tumor Cells

This research builds on a 2015 research paper where Marchetti’s lab isolated four distinct circulating tumor cell subsets that were implicated in breast cancer cell dormancy.

Viable breast cancer cells can remain dormant in the patients’ bone marrow or other organs like the brain, lungs and liver, even decades after a primary tumor is surgically removed. These scattered cells are often undetectable by traditional clinical tools, making it nearly impossible to detect and treat metastatic disease while still amenable to therapy.

Comparison between CTC and primary breast cancer transcriptomes

Comparison between CTC and primary breast cancer transcriptomes.
Credit: Debasish Boral et al

The Houston Methodist researchers are now focused on broadening the study patient population, with the end goal of transforming this information into the development of two kinds of non-invasive liquid biopsies that could be used by treating physicians: a screening method to predict brain metastasis before the disease is detectable by current diagnostic standards (MRI); and another to monitor treatment efficacy in real-time in those patients diagnosed with brain metastasis.

Debasish Boral, Monika Vishnoi, Haowen N. Liu, Wei Yin, Marc L. Sprouse, Antonio Scamardo, David S. Hong, Tuan Z. Tan, Jean P. Thiery, Jenny C. Chang & Dario Marchetti
Molecular characterization of breast cancer CTCs associated with brain metastasis
Nature Communications 8, Article number: 196 (2017) doi:10.1038/s41467-017-00196-1

Top Image: Houston Methodist