A research team at Yonsei University College of Medicine has discovered a new target anticancer drug lead that inhibits the activity of FAK (focal adhesion kinase) and FLT3 (FMS-like tyrosine kinase 3).

A research team at Yonsei University College of Medicine, led by Professor Shim Tae-bo, has discovered a new candidate to treat metastatic breast cancer and acute myeloid leukemia.
A research team at Yonsei University College of Medicine, led by Professor Sim Tae-bo, has discovered a new candidate to treat metastatic breast cancer and acute myeloid leukemia.

The team expects that this substance will help develop targeted treatments for breast cancer and leukemia.

According to the university, FAK, a local adhesion-related protein kinase involved in cell adhesion and migration processes, plays an important role in cell survival and cell-to-cell adhesion.

“Overexpression of FAK induces primary and metastatic tumors in various tissues, including breast, ovarian, colorectal, and brain cancer,” the university said. “Therefore, inhibition of FAK can prevent the metastasis and growth of cancer cells.”

FAK also plays an important role in anti-tumor immunity and angiogenic functions that help cancer tissues stop growing in the body. However, while researchers expect that the development of FAK protein inhibitors will inhibit cancer development and metastasis, there have not been any FAK inhibitory drugs developed.

The team, led by Professor Sim Tae-bo of the Department of Biomedical Sciences, designed and synthesized 40 new inhibitors to derive a new target anticancer drug leader from regulating FAK protein. The researchers then discovered an optimal representative compound was selected through a structure-activity relationship study.

After administering the representative compound to a triple-negative breast cancer mouse model, the researchers confirmed decreased breast cancer mass. In addition, when they orally administered the representative compound to a mouse model, breast cancer metastasis through the lymph nodes was reduced.

Also, the research team applied the representative compound to FLT3 mutation, which occurs most commonly in acute myeloid leukemia (AML). About 40 percent of patients with acute myeloid leukemia carry the FLT3 mutation. Although FLT3 inhibitors targeting FLT3 mutations have previously received approval from the U.S. Food and Drug Administration, there has been a need to develop inhibitors capable of overcoming resistance due to the emergence of mutants resistant to existing inhibitors.

As a result of a trial on a tumor-transplanted mouse model harboring the FLT mutation, the researchers confirmed that an oral administration of the treatment compound reduced the volume of the transplanted FLT mutation-bearing tumor by more than 90 percent.

“We could derive a new lead substance that can effectively inhibit FAK and FLT3 mutants through this study,” Professor Sim said. “In subsequent studies, we expect to develop a novel drug that can inhibit FAK and FLT3 resistance mutations.”

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