Breakthrough: Breast cancer relapse linked to fat metabolism

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Although great strides have been made in the treatment of breast cancer, relapse is still a major issue that has defied investigation. A new study might pave the way to reducing relapse rates by identifying rogue cells earlier.

Cancer is no longer a death sentence; it is now possible to successfully treat a range of cancer types and, consequently, survival rates are on the up.

In breast cancer, for instance, the 5-year survival rate is 89 percent, and the 10-year survival rate is 83 percent. In fact, according to one study, the 10-year survival rate for breast cancer has tripled in the past 60 years.

As primary care improves and our knowledge of the disease grows, rates are likely to improve steadily. However, breast cancer is still “the second leading cause of cancer-related death in women.”

Although advances in treating breast cancer are constantly being made, one particular facet of the disease is particularly difficult to understand and prevent: relapse.

Understanding breast cancer relapse

Although improved cancer treatments mean that many patients survive the initial tumor, relapse is now the leading cause of death among breast cancer patients.

Surgical removal of malignant tissue and chemotherapy both aim to destroy cancerous cells but, often, some residual cells will survive. These surviving cells can lead to a regrowth further down the line.

The difficulty is that these cells do not seem untoward until they reinitiate growth. This makes preempting relapse incredibly difficult and, because the cells appear normal, isolating them and studying the process is also challenging.

A paper, published this week in the Journal of Clinical Investigation, gives new insight into this process and promises to make identifying these cells a possibility.

The team used a mouse model, alongside a relatively new technique involving so-called organoids, or organotypic structures. Organoids are small collections of cells that are cultured outside of the body. They mimic the structure and function of organs and have proven useful for testing drugs, examining organ development, and investigating personalized treatments.

Researchers from the European Molecular Biology Laboratory, led by Martin Jechlinger, examined the gene transcription profiles and metabolism pathways in these residual cells. “We found that residual cells have molecular traits that clearly distinguish them from normal breast tissue, and seem to cause relapse.”

Relapse and lipid metabolism

The researchers identified a chemical signature in the way that residual cells metabolized lipids. The altered process contributed to maintaining high levels of reactive oxygen species, which are molecules known to harm DNA. The team believes that this may play a role in triggering a relapse.

To investigate the importance of these metabolic changes, the team reversed the alterations. Jechlinger notes, “When we treated those features in mice, their tumors were less likely to recur.”

Having identified this difference in residual cells, they compared their findings in mice and organoids with pre- and post-treatment biopsies from breast cancer patients. In this task, they received help from the National Centre for Tumor Diseases in Heidelberg, Germany, and the European Institute of Oncology in Milan, Italy. As expected, the results were replicated: the same alterations in fat metabolism were observed in the human tissue.

“Our results suggest that residual cells retain an ‘oncogenic memory’ that could be exploited to develop drugs against breast cancer recurrence.”

Martin Jechlinger

Other scientists will now be able to examine these cellular differences and get to the bottom of how lipid metabolism might influence cancer relapse. Kristina Havas, one of the scientists involved in the current project, has high hopes, saying, “Every patient is different, and every story is unique, but our results suggest that lipid metabolism is an exciting therapeutic target to reduce breast cancer recurrence.”

Learn how organoids have been used to study stomach-related cancers.

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