Title: Unravelling the Secrets of Brain Metastasis: A Closer Look at Vascular Cells
Lay Summary: A new study on brain metastasis published in the journal Cancer Cell (published 8th of January 2024). In the world of cancer research, understanding how cancer spreads to the brain is a crucial and challenging area. Spread of cancer cells to the brain is usually referred to as brain metastasis or secondary cancer to the brain. A recent study titled “Interrogation of endothelial and mural cells in brain metastasis reveals key immune-regulatory mechanisms” sheds new light on this process. Here is what the research tells us in simpler terms:
Key Findings:
- Exploring Brain Metastasis at the Cellular Level: Researchers examined individual cells in the blood vessels of the brain where metastasis occurs (known as brain metastasis) and compared them with cells in healthy brains. They focused on two main types of cells: endothelial (lining the inside of blood vessels) and mural (supporting cells around vessels).
- Identifying Unique Cell Subtypes in Brain metastasis: The study found that in Brain metastasis, there are specific subtypes of endothelial and mural cells that are quite different from those in non-cancerous brain tissue. Some of these unique cell types seem to play a role in regulating the immune system.
- Combining Human and Mouse Data for Better Understanding: By combining data from human patients with experiments in mouse models, researchers created a comprehensive platform to study and identify potential targets for treating brain metastasis.
- CD276: A Promising Therapeutic Target: One significant discovery was the identification of CD276, a molecule found to be highly active in brain metastasis’s blood vessel cells. CD276 is involved in immune checkpoint mechanisms – processes that cancer cells can exploit to avoid being attacked by the body’s immune system.
- Potential for New Treatments: The study tested antibodies that block CD276 in preclinical trials and found that they could extend survival. This suggests that targeting CD276 might be a promising approach in developing new treatments for brain metastasis.
What Does This Mean for Patients?
This research gives us a deeper understanding of the complex environment where brain metastasis occurs, particularly focusing on the blood vessels. The discovery of CD276 as a key player opens new doors for potential treatments. While there is still a lot to learn, these findings are a significant step towards developing therapies that could better manage or even prevent the spread of cancer to the brain.
Title: Understanding Breast Cancer’s Spread to Brain and Spinal Cord Lining: New Insights from Genomic Profiling
Lay Summary:
A recent study published in Nature Communications (published 16 November 2023) delves into a particularly challenging aspect of breast cancer known as leptomeningeal metastasis. Leptomeningeal Metastasis in Breast Cancer: This occurs when breast cancer cells spread to the leptomeninges, the delicate membranes covering the brain and spinal cord. This is a serious and complex condition, often difficult to treat and study. Lobular Breast Cancer: This type of breast cancer originates in the milk-producing lobules of the breast. It is known for its tendency to spread more diffusely and be harder to detect than other types of breast cancer.
Study Overview:
The study aimed to understand the genetic changes in breast cancer cells when they metastasize to the leptomeninges. Researchers analyzed tumour DNA from the cerebrospinal fluid (CSF) of patients with Leptomeningeal Metastasis. The study found that a significant number of Leptomeningeal Metastasis cases (81%) had genetic alterations that could potentially be targeted with therapy.
- Looking at Cancer DNA: Researchers examined DNA from cancer cells found in the spinal fluid of patients with Leptomeningeal Metastasis.
- Finding Changes: They discovered that most of these cancer cells had special changes in their DNA, similar to a type of breast cancer called lobular breast cancer.
- Growing Cancer Cells in the Lab: The team managed to grow these cancer cells in a way that mimics how they grow in the body. This helps scientists study the disease more closely.
Why It Matters:
- Better Understanding: Knowing that these cancer cells change to look more like lobular breast cancer helps doctors think about new ways to treat them.
- Hope for New Treatments: The study’s methods give scientists tools to test treatments that could specifically target these changes in cancer cells.
Title: Unraveling How Breast Cancer Cells Resist Chemotherapy in the Brain Without Prior Treatment
A recent study published in Science Advances journal (published 18 Oct 2023) delves into a critical issue in cancer treatment: why some breast cancer brain metastases (BCBMs) resist chemotherapy even before any treatment begins. This phenomenon, known as intrinsic chemo resistance, poses a significant challenge in cancer therapy. Let us break down what the study discovered:
Understanding Intrinsic Chemo-resistance:
It has often thought that cancer cells develop resistance to chemotherapy as a direct response to the treatment itself. However, this study investigates how breast cancer cells that spread to the brain might inherently resist chemotherapy, even without prior exposure to these drugs.
Study Findings:
The team studied breast cancer cells that had spread to the brain in mice without previous chemotherapy treatment.
- Key Discovery: These cancer cells exhibited a unique behaviour called vascular mimicry, where they imitate blood vessel cells (this has been shown in previous studies too as a mechanism of how cancer cells attach and invade the brain). Alongside this, they expressed high levels of a protein known as Breast Cancer Resistance Protein (BCRP).
- This protein is typically found in brain endothelial cells (cells lining the blood vessels in the brain) and is known for pumping out certain drugs, including chemotherapy agents like doxorubicin.
- The overexpression of Breast Cancer Resistance Protein in these metastatic breast cancer cells in the brain provided them with a shield against the effects of these chemotherapy drugs.
Why This Matters: This study sheds light on a previously underexplored aspect of cancer resistance. Understanding that breast cancer cells can inherently resist chemotherapy due to factors like Breast Cancer Resistance Protein expression helps in rethinking treatment strategies. It suggests that targeting this protein could be a key to overcoming this resistance in breast cancer brain metastases, potentially leading to more effective therapies for patients who have not yet undergone chemotherapy.
Sci Adv . 2023 Oct 20;9(42):eabp9530. doi: 10.1126/sciadv.abp9530. Epub 2023 Oct 18.PMID: 37851804
Decoding the Role of RNA Methylation in Breast Cancer: A Simplified Look at Recent Research
Our group recently published a paper in a cancer journal Cancer Communications: https://onlinelibrary.wiley.com/doi/10.1002/cac2.12407 (anyone interested and without access let me know, happy to send a PDF).
In a groundbreaking study, our researchers have taken a closer look at how changes in RNA, specifically through a process called RNA methylation, can affect the progression of breast cancer to a more severe stage known as metastasis. This study is particularly important because, until now, much of the focus has been on DNA changes in cancer, leaving the role of RNA somewhat in the shadows.
What is RNA Methylation? Simply put, RNA methylation involves small chemical changes in RNA, a molecule closely related to DNA. These changes can affect how genes are expressed, meaning how they behave or instruct the cell.
Focus on ER+ Breast Cancer The study concentrated on a type of breast cancer known as estrogen receptor-positive (ER+) or hormone receptor (HR+) breast cancer, which is sensitive to estrogen and forms the majority of breast cancer cases. The researchers looked at how RNA methylation impacts the progression of this cancer type to metastasis, where cancer spreads to other parts of the body.
Key Discoveries:
- FTO Protein’s Role: We found that higher levels of a protein called FTO are linked with a worse outlook for patients. In particular, FTO was significantly associated with lower overall survival and progression-free survival, meaning patients with higher FTO levels had a higher chance of the cancer progressing or returning.
- Impact of FTO Blocking/Inhibition: Interestingly, when we tested drugs that inhibit FTO, we saw promising results. These drugs, particularly when combined with another cancer drug (afatinib), were effective in reducing cancer cell growth in models of breast cancer that had spread to the brain.
- RNA Changes in Metastasis: The study also showed that changes in RNA methylation patterns were connected with the cancer spreading to the brain, indicating a potential area for future therapies.
What Does This Mean? This research opens up new avenues in understanding and treating advanced breast cancer. It suggests that targeting RNA methylation, particularly focusing on the FTO protein, could be a new strategy to combat breast cancer that has spread or is resistant to other treatments.
In essence, this study sheds light on a previously underexplored area of breast cancer research and offers hope for developing new therapies against this challenging disease
DV Research Insights 