Yibin Kang, PhD

Targeting metastatic breast cancer at the nexus of cancer progression and immune response.

Impact

Metastatic breast cancer (MBC)—when breast cancer spreads to other organs—is incurable and responsible for the majority of breast cancer deaths. Dr. Kang and his team identified a protein, metadherin (MTDH), that is generated by many breast tumors and its presence predicts poor outcome for patients. The team found that MTDH promotes both metastasis and chemotherapy resistance in cancer cells and helps tumors evade the immune system, making it a promising target for therapy. Dr. Kang’s team is exploring whether blocking MTDH could help promote an anti-tumor response by the immune system. The findings from this research may lead to a new immunotherapy approach for metastatic breast cancer.

Progress Thus Far

Dr. Kang and his team have identified a previously unrecognized link between fat metabolism in the liver and the strength of the immune system in fighting breast cancer. By engineering advanced breast cancer models, they have found that blocking MTDH in both immune and liver cells, the immune cells – especially cancer-fighting CD8+ T cells – become more capable of attacking tumors. These immune cells show improved energy production and survival, which translates into stronger antitumor responses. These discoveries suggest that targeting MTDH could re-energize the immune system and overcome barriers that have made immunotherapy less effective for patients with breast cancer, particularly those with metastatic disease.

What’s next

In the coming year, Dr. Kang and his team will further explore how tumors communicate with the liver to disrupt normal fat metabolism and weaken the immune response. One focus will be on extracellular vesicle particles (EVPs). EVPs are tiny particles released by cancer cells that may carry signals to the liver and immune system through MTDH. Dr. Kang and his team will study how these signals alter liver function and if blocking MTDH restores balance.

The team will also test antisense oligonucleotides (ASOs), a new type of treatment that directly regulates disease-causing genes and their variants. They have developed ASOs that effectively reduce MTDH expression in liver and CD8+ T cells. These ASOs will be evaluated alone and in combination with existing immunotherapy drugs to assess their potential in reducing tumor growth and improving immune activity. Their goal is to develop a treatment strategy that not only targets the tumor but also disrupts the support network that helps metastatic breast cancer thrive, offering hope for more effective therapies.