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13 December 2023

New insights into cancer that spreads over brain and spinal cord lining

A new publication on leptomeningeal metastasis (LM), a condition where cancer cells spread over the lining of the brain and down the spinal cord, reveals new avenues for research and targets for future therapies.

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A new study on the cancer leptomeningeal metastasis (LM) has revealed novel insights into its structure and genetics, providing new avenues for research and targets for future therapies.

Cancer cells can develop in a particular part of the body and then spread to another part in a process known as metastasis. LM is a condition that occurs when cancer metastasises to the thin membrane covering the brain and spinal cord, known as the leptomeninges.

It is one of the most devastating versions of metastasis that affects the brain, with an average survival rate of just 3 months after diagnosis. The short timeframe makes medical intervention or collecting biopsies incredibly difficult, as clinicians have to open the skull to access the delicate linings around the brain and spinal cord. Consequently, researchers know little abouts the genetics or biological mechanisms that drive LM.

In this new study led by Amanda Fitzpatrick, researchers collected samples of cerebrospinal fluid from breast cancer patients with LM. From the fluid, the researchers were able to extract and analyse the DNA of LM cancer cells.

The results, published in Nature Communications, showed that LM cells will spread early within a patient from the original tumour, with their LM cells developing mutations that are not in the original tumour. Specific genes, including ones that control the cell shape and how they stick to each other, were found to be altered.

Authors also observed that these cells developed some features associated with lobular breast cancers. This knowledge could help identify patients at a greater risk of developing LM, and give us a greater understanding of its structure and targets for new therapeutic approaches.

Alongside these insights, the authors developed cultures of LM cancers from the cells isolated by the patient’s CSF, which has traditionally been very difficult to accomplish. This new method will provide an easier process for research to grow cancer cultures for experimentation.

This discovery highlights that LM has a unique biology, showing differences in how cells stick to each other and regulate their shape. This is really exciting as it presents a potential Achilles Heel for targeting this type of spread. We are now able to grow the tumour cells from patient’s spinal fluid to model this disease - and this will allow us to test new therapies before introducing them to clinical trials. Given that two thirds of patients in this study had controlled cancer outside the brain, being able to control LM with better treatments will be crucial in helping patients live longer with cancer”

Dr Amanda Fitzpatrick, honorary senior lecturer

Following its publication Dr Amanda Fitzpatrick and her laboratory are now focused on further research to understand how these genetic mutations help LM cells grow and how they can be targeted to identify novel therapies.

Read the full paper: Genomic profiling and pre-clinical modelling of breast cancer leptomeningeal metastasis reveals acquisition of a lobular-like phenotype.