April 21, 2024

New Pathway Discovered for Treating Breast Cancer Bone Metastases

Researchers at Rice University have uncovered a promising new immunological pathway for treating stubborn bone tumors, a common form of metastases in breast cancer patients. More than 70% of individuals with metastatic breast cancer will experience the spread of cancer cells to the bones, leading to skeletal-related events such as bone pain, fractures, and hypercalcemia. The study, led by Yixian Wang, a graduate student in the Han lab at Rice University, has been published in the Proceedings of the National Academy of Sciences.

While there are several immunotherapies available that could benefit breast cancer patients with metastases, they are not effective in treating bone tumors. Breast cancer affects over 240,000 individuals annually in the United States, with approximately one-quarter experiencing metastasis where cancer cells spread to other parts of the body.

Checkpoint inhibitors, a type of immunotherapy, can reveal hidden tumors, allowing the immune system to target and eliminate abnormal cells. However, these inhibitors do not work for all patients, and clinical trials have shown limited to no response when used to treat bone metastases. Seeking to overcome this challenge, Han Xiao, an associate professor of chemistry, biosciences, and bioengineering at Rice University, and his team set out to identify an alternative pathway that could effectively eradicate these stubborn bone metastases.

The researchers discovered a unique glyco-immune checkpoint axis involving a protein called sialic acid-binding Ig-like lectin (Siglec)-15, which plays a crucial role in suppressing immune cells in the bone. After observing a significant upregulation of Siglec-15 in bone tumor samples from breast cancer patients, the team demonstrated that this receptor plays a pivotal role in hiding bone tumors from immune surveillance.

Unlike currently approved checkpoint inhibitors, which are mediated by protein-protein interactions that suppress immune cells, Siglec-15 functions as a glyco-immune checkpoint inhibitor. Instead of binding to proteins, Siglec-15 binds to sugars present on cell surfaces, allowing it to suppress the immune system. This discovery opens up avenues for future treatment options for bone cancers.

To further investigate the interaction between Siglec-15 and the bone tumor microenvironment, Xiao’s team conducted several cell culture experiments. They found that Siglec-15 is involved in communication between tumor cells and crucial immune cells like T-cells and macrophages, as well as bone-specific cells called osteoclasts.

These glycolipids and glycoproteins are found on all cells, and we know that they play a vital role in modulating the immune system, said Xiao. This discovery presents us with an opportunity to delve deeper into the study of glyco-immune checkpoint inhibitors and identify those that can help prevent bone tumors from evading immune recognition.

This breakthrough research offers new hope for developing innovative treatments for breast cancer bone metastases. By targeting the glyco-immune checkpoint axis involving Siglec-15, researchers may be able to enhance immune response and improve outcomes for patients with bone tumors. Further studies and clinical trials are needed to explore the potential of this pathway and develop effective therapies to combat bone metastases in breast cancer patients.

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1. Source: Coherent Market Insights, Public sources, Desk research
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