A New Way to Target Secondary Breast Cancer That Has Spread to the Brain

Summary: Researchers have identified a potential new target to treat breast cancer that has spread to the brain using existing drugs.

Source: RCSI

A study led by researchers at RCSI University of Medicine and Health Sciences and the Beaumont RCSI Cancer Centre (BRCC) has revealed a potential new way to treat secondary breast cancer that has spread to the brain, using existing drugs.

The study, published in Nature Communications, was funded by Breast Cancer Ireland with support from Breast Cancer Now and Science Foundation Ireland.

Most breast cancer related deaths are a result of treatment relapse leading to spread of tumors to many organs around the body. When secondary breast cancer, also known as metastatic breast cancer, spreads to the brain it can be particularly aggressive, sometimes giving patients just months to live.

This shows the outline of a head and a brain
Most breast cancer related deaths are a result of treatment relapse leading to spread of tumors to many organs around the body. Image is in the public domain

The RCSI study focused on genetically tracking the tumor evolution from diagnosis of primary breast to the metastatic spread in the brain in cancer patients. The researchers found that almost half of the tumors had changes in the way they repair their DNA, making these tumors vulnerable to an existing type of drug known as a PARP inhibitor. PARP inhibitor drugs work by preventing cancer cells to repair their DNA, which results in the cancer cells dying.

“There are inadequate treatment options for people with breast cancer that has spread to the brain and research focused on expanding treatment options is urgently needed. Our study represents an important development in getting one step closer to a potential treatment for patients with this devastating complication of breast cancer,” commented Professor Leonie Young, the study’s Principal Investigator.

“By uncovering these new vulnerabilities in DNA pathways in brain metastasis, our research opens up the possibility of novel treatment strategies for patients who previously had limited targeted therapy options,” said study author Dr. Damir VareŇ°lija.

About this brain cancer research news

Author: Jane Butler
Source: RCSI
Contact: Jane Butler – RCSI
Image: The image is in the public domain

Original Research: Open access.
Mapping molecular subtype specific alterations in breast cancer brain metastases identifies clinically relevant vulnerabilities” by Nicola Cosgrove et al. Nature Communications


Abstract

Mapping molecular subtype specific alterations in breast cancer brain metastases identifies clinically relevant vulnerabilities

The molecular events and transcriptional plasticity driving brain metastasis in clinically relevant breast tumor subtypes has not been determined.

Here we comprehensively dissect genomic, transcriptomic and clinical data in patient-matched longitudinal tumor samples, and unravel distinct transcriptional programs enriched in brain metastasis. We report on subtype specific hub genes and functional processes, central to disease-affected networks in brain metastasis.

Importantly, in luminal brain metastases we identify homologous recombination deficiency operative in transcriptomic and genomic data with recurrent breast mutational signatures A, F and K, associated with mismatch repair defects, TP53 mutations and homologous recombination deficiency (HRD) respectively. Utilizing PARP inhibition in patient-derived brain metastatic tumor explants we functionally validate HRD as a key vulnerability.

Here, we demonstrate a functionally relevant HRD evident at genomic and transcriptomic levels pointing to genomic instability in breast cancer brain metastasis which is of potential translational significance.

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