Changing the standard dose and timing of two therapies greatly cut tumor relapse and reduced side effects in mouse models of kinase mutated breast cancer and lung cancer, UT Southwestern Simmons Cancer Center researchers have found.

The study published last month in Science Immunology suggests that giving the two therapies as short course, first-line treatment might work better than the current practice of providing one treatment early and the other treatment only if tumors relapse.

This study reveals the importance of the proper combination and timing of tyrosine kinase inhibitors and immunotherapy such as the programmed death-ligand 1 (PD-L1) inhibitor, also known as immune checkpoint blockade, said corresponding author Dr. Yang-Xin Fu, Professor of Pathology, Immunology, and Radiation Oncology and a member of the Harold C. Simmons Comprehensive Cancer Center.

Many cancers have high and abnormal tyrosine kinase activities. Tyrosine kinase inhibitors, or TKIs – which target specific cancers – are a common first-line treatment for rapidly shrinking tumors such as those associated with kinase-driven breast cancer and lung cancer. But tumor relapse or resistance often occurs. The standard of care is to use TKIs first and then use immunotherapy such as PD-L1 inhibitors after relapse occurs, Dr. Fu explained. Our study showed that immunotherapy should be used together with the TKIs as the first-line – not second-line or third-line – treatment. We also demonstrated that the dose and timing of the TKI is important.

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