BEZ235 (dactolisib)

Overview

BEZ235 (dactolisib) is a dual PI3K/mTOR inhibitor that blocks both the PI3K catalytic subunits and mTORC1/mTORC2. It was investigated as a potential therapy in cancers with activated PI3K/mTOR signaling.

Evidence in the corpus

• Dual PI3K/mTOR inhibitor BEZ235 substantially inhibited proliferation of all hypodiploid ALL tumors tested ex vivo (both near haploid and low hypodiploid subtypes), consistent with PI3K/mTOR pathway dependence; effect was comparable to the pan-PI3K inhibitor GDC-0941, and MEK inhibitors were ineffective PMID:23334668.

Resistance mechanisms

• Single-arm Ras/MAPK inhibition via MEK inhibitors was insufficient, confirming that dual PI3K/mTOR blockade is required for effective anti-proliferative activity in hypodiploid ALL PMID:23334668.

Cancer types (linked)

• BLL — hypodiploid ALL (both near haploid and low hypodiploid subtypes); ex vivo sensitivity established.

Sources

• PMID:23334668

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