Mitochondrial protein may improve selective liver cancer treatment

Hepatocarcinoma is the most commonly diagnosed form of liver cancer. It is an aggressive, fast growing cancer with a 5-year survival rate of only 15%. Thomas Jefferson University researcher Gyorgy Hajnoczky, MD/Ph.D., and his team recently found that a protein in mitochondria called VDAC2, may be a key player in making liver cancer cells more susceptible to cell death than normal liver tissue, offering a promising avenue for targeted therapy.

Dr. Hajnoczky’s group previously found that VDAC2 recruits another protein called BAK, a key regulator in mitochondria-dependent cell death.

“The mitochondrion has a larger purpose than being the ‘powerhouse of the cell’,” says Dr. Hajnoczky. “They also play a role in maintaining a healthy cell population by facilitating the death of unhealthy cells.”

In the new study published in Nature Communications, the team led by researchers at Jefferson’s Mitocare Center, found that liver cancer cells have higher levels of VDAC2 compared to normal liver cells, making them susceptible to existing treatments targeting BAK-dependent cell death.

Combining two pre-clinical drugs that target BAK shrank tumors of liver cancer cells with high levels of VDAC2, while leaving normal tissues intact in mice. However, mice with tumors lacking VDAC2 did not respond to this treatment and showed cancer-cell growth.

“It may be that VDAC2 is the ‘Achilles heel’ of liver cancer, presenting a vulnerability that can be therapeutically exploited, while leaving normal liver cells intact,” says Dr. Hajnoczky, who is also a member of the Sidney Kimmel Medical College.

Although this research is exciting, it is still in the early stages. Dr. Hajnoczky and his team hope that future studies will reveal more about how VDAC2 is involved in primary and metastatic liver cancers, paving the way for effective therapeutic strategies for patients.