Inhibiting the LLGL2-SLC7A5-YKT6 complex for breast cancer

INDICATION: Breast cancer

Patient sample, cell culture and mouse studies suggest inhibiting the LLGL2-SLC7A5-YKT6 leucine transporter complex could help treat breast cancer. In patients with estrogen receptor- and progesterone receptor-positive breast cancer, high tumor levels of LLGL2 mRNA were associated with poor survival, and in patients with estrogen receptor-positive breast cancer, high tumor levels of LLGL2 or SLC7A5 protein were associated with poor survival. In two human breast cancer cell lines, an shRNA targeting LLGL2 or SLC7A5 decreased proliferation compared with a non-targeting shRNA. In one of the lines, an shRNA targeting YKT6 decreased proliferation. In a xenograft mouse model of breast cancer, tumor-specific knockout of LLGL2 or SLC7A5 or the SLC7A5 inhibitor JPH203 decreased tumor growth compared with normal LLGL2 and SLC7A5 expression or vehicle. Next steps could include testing LLGL2, SLC7A5 and YKT6 inhibitors in patient-derived xenograft (PDX) models of breast cancer...