Yonsei University discovers new substance to treat metastatic breast cancer

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

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

The team expects this substance to 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.

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

FAK also plays an important role in anti-tumor immunity and angiogenic functions that help cancerous tissue to stop growing in the body. However, while researchers expect the development of FAK protein inhibitors to inhibit cancer development and metastasis, no FAK inhibitor drugs have been 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 cancer drug targeting the regulation of the FAK protein. The researchers then found that an optimal representative compound had been selected through a study of the structure-activity relationship.

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

In addition, the research team applied the representative compound to the FLT3 mutation, which occurs most often 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 already received approval from the United States Food and Drug Administration, it has been necessary to develop inhibitors capable of overcoming resistance due to the emergence of resistant mutants. existing inhibitors.

Following a trial on a transplanted mouse model of a tumor harboring the FLT mutation, researchers confirmed that oral administration of the treatment compound reduced the size of the tumor bearing the transplanted FLT mutation by more than 90%. .

“We could derive a new lead substance capable of effectively inhibiting FAK and FLT3 mutants through this study,” said Professor Sim. “In subsequent studies, we plan to develop a new drug capable of inhibiting FAK and FLT3 resistance mutations. “

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