azd8055

Overview

AZD8055 is an ATP-competitive inhibitor of mTOR (mechanistic target of rapamycin) that blocks both mTORC1 and mTORC2 complexes, inhibiting downstream S6K and 4EBP1 phosphorylation. It has been investigated as a senolytic agent to selectively kill senescent cancer cells.

Evidence in the corpus

• Selectively inhibited S6K and S6 phosphorylation in KRASG12C-amplified colorectal cancer cells that entered oncogene-induced senescence after sotorasib + cetuximab withdrawal; showed enhanced cytotoxicity in the senescent (drug-off) condition compared with continuous drug exposure (P ≤ 0.0001), establishing mTOR inhibition as a candidate senolytic strategy for KRASG12C-amplified resistant tumors PMID:36355783

Resistance mechanisms

Cancer types (linked)

• COADREAD — investigated as senolytic in KRASG12C-amplified, drug-resistant colorectal cancer models after sotorasib + cetuximab withdrawal

Sources

• PMID:36355783

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