New Strategy Boosts Immunotherapy for Aggressive Ovarian Cancer

A preclinical study has revealed a promising approach to overcome resistance to immunotherapy in high-grade serous ovarian cancer, the most common and aggressive form of the disease. Researchers have identified that blocking the focal adhesion kinase (FAK) protein can enhance the immune system’s ability to detect and attack ovarian tumors.

The Challenge of Ovarian Cancer Immunotherapy

Ovarian cancer often suppresses the immune system, hindering the effectiveness of immunotherapies designed to boost immune cell activity. Even when immune cells are activated, they may struggle to recognize and react to the tumor. “Even if you boost the capability of immune cells, a treatment will have limited success if the cells struggle to recognize and react to the tumor,” explained Dr. David Schlaepfer, a professor in the department of OBGYN and Reproductive Sciences at the UC San Diego Moores Cancer Center.

FAK: A Key Player in Immune Resistance

Prior research has pinpointed focal adhesion kinase (FAK) as a critical protein contributing to immune evasion in ovarian cancer. Genetic mutations lead to an overabundance of FAK in more than three out of four cases of high-grade serous ovarian cancer, and this overabundance is linked to reduced patient survival. Sanford Burnham Prebys and University of California San Diego scientists have been investigating FAK’s role in this resistance.

Triple Combination Therapy Shows Promise

Researchers at Sanford Burnham Prebys and UC San Diego conducted a study published in Cell Reports on February 25, 2026, demonstrating that a triple combination therapy – a FAK inhibitor combined with chemotherapy and immunotherapy – significantly improved outcomes in a mouse model of aggressive, chemotherapy-resistant ovarian cancer. Cell Reports

The combination treatment led to controlled tumor growth and modified the immune response, increasing the infiltration of T and B cells into the tumor.

How FAK Inhibition Works

The research team discovered that blocking FAK alters the behavior of macrophages, immune cells traditionally known for engulfing bacteria and cellular debris. With FAK blocked, macrophages began sending chemical signals, specifically a signaling protein called CXCL13, that helped coordinate an immune attack against the tumor. This recruitment of immune cells formed structures called tertiary lymphoid structures, acting as temporary immune bases within the tumor.

“Once it was established that genetically or pharmacologically targeting FAK improved the ability of the immune system to recognise and attack ovarian tumour models, then we needed to figure out how this worked,” said Dr. Kevin Tharp, an assistant professor in the Cancer Metabolism and Microenvironment Program at Sanford Burnham Prebys. Drug Target Review

Future Directions

While these findings are promising, further research is needed before clinical trials in patients can begin. Future studies will focus on exploring combination therapies utilizing FAK inhibitors alongside existing chemotherapy and immunotherapy treatments. Researchers believe this approach holds significant potential for patients with advanced ovarian cancer who have not responded to standard treatments. “I think that this represents an essential treatment opportunity for patients who have progressed and not responded to the standard of care. It’s an extreme clinical need,” added Tharp. News Medical