Study highlights new target and potential therapy for treatment-resistant cancers

University of Kentucky Markey Cancer Center researchers have discovered a promising new way to combat therapy-resistant cancers by targeting a specific protein modification, according to a study published in the International Journal of Biological Sciences.

The research team, led by Vivek Rangnekar, Ph.D., professor and Alfred Cohen Chair in Oncology Research in the UK College of Medicine, focused on a protein called S6K1, which is found to be activated at high levels in many cancer types including lung, prostate, colon and esophageal cancer.

When this protein becomes activated by "phosphorylation," or modification by adding phosphate groups, it helps cancer cells survive and resist treatment.

Through screening approximately 1,400 Food and Drug Administration-approved drugs, the team identified an antihistamine called ebastine that could target some cancer cells. They then developed a modified version called Super-ebastine (Super-EBS), which was far more effective at inhibiting diverse cancer cells and worked by blocking the phosphorylated S6K1.

In lab tests, Super-EBS was effective against over 95% of cancer cell lines tested, including resistant forms of lung and prostate cancers, while showing minimal effects on healthy cells. Mouse studies showed the compound could inhibit tumor growth without causing significant side effects.

Cancer cells often become resistant to treatment by changing their characteristics in a process called cellular plasticity. The study found that as cancers develop this resistance, they become more dependent on phosphorylated S6K1, making them more vulnerable to the new treatment approach. The research opens the doors for future studies on Super-EBS and related compounds to develop targeted treatments for therapy-resistant cancers.

The findings could eventually lead to more treatment options for patients who have developed resistance to standard therapies, says Rangnekar.

"By understanding how these resistant cancers rely on phospho-S6K1 for survival, scientists can develop new targeted treatments that may help patients who currently have limited options," Rangnekar said.