Br J Cancer: SBI-756 and venetoclax: a new combination of B-cell lymphoma treatments

mTOR is the main regulatory factor for cell growth and proliferation and a target for the treatment of cancer and other diseases.
mTORC1 and mTORC2 are two compounds that promote the mTOR signal transducting path.
previous studies have shown that mTOR activation mutations occur in diffuse large B-cell lymphoma (DLBCL), and increased activity of mTORC1 is associated with chemotherapy resistance and poor prognosis of acute B-lymphoblastic leukemia (B-ALL).
BCL2 inhibitor Venetoclax is a small molecule BH3 analog drug that selectively binds to BCL2 and inhibits its function.
has shown some efficacy in a variety of hemolytic malignancies, with the highest response rate in inert blood cancers such as chronic lymphocytic leukemia.
in DLBCL, patients treated with Venetoclax had a lower response rate.
the study, researchers tested the sensitivity of cap-dependent mRNA translation inhibitors to the apoptosis effects of DLBCL and sleeve lymphoma (MCL).
researchers compared the effects of mTOR kinase inhibitors (TOR-KI) MLN0128 and SBI-756.
SBI-756 is a compound that targets scaffolding protein eIF4G1 in eIF4F complexes.
SBI-756 blocks eIF4E-eIF4G interactions and cap-dependent translation Researchers have found that Venetoclax combined with SBI-756 to process DLBCL and MCL cells to induce apoptosis and enhance The effectiveness of Venetoclax.
SBI-756 blocks the binding of eIF4E-eIF4G1 and inhibits cap-dependent translation, but does not affect phosphorylation of mTOR substrates.
SBI-756 can still make cells sensitive to Venetoclax in TOR-KI drug-resistant DLBCL cells that lack eIF4E binding protein 1.
SBI-756 can selectively reduce the translation of mRNA that encodes RNA and translation factors, resulting in a decrease in the rate of protein synthesis in sensitive cells.
when normal lymphocytes are treated with SBI-756, only B cells are less active, which is associated with a decrease in protein synthesis rate.
SBI-756 makes Venetoclax therapy sensitive, the results reveal a new combination for the treatment of invasive lymphoma and use preclinical models to determine the efficacy and selectivity of the combination.
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