Insulin-like growth factor receptor (IGF-1R)-targeted monoclonal antibodies (mAb) have shown limited anticancer therapeutic efficacy. In this study, Shin and colleagues investigated the mechanisms of resistance to a fully humanized anti-IGF-1R mAb cixutumumab in head and neck squamous cell carcinoma (HNSCC). They found that resistance to IGF-1R inhibition by cixutumumab was associated with Akt/mammalian target of rapamycin (mTOR)-mediated de novo protein synthesis of EGFR, Akt1, and survivin and activation of the EGFR pathway, and cotargeting IGF-1R/mTOR had synergistic antitumor effects in vitro and in vivo. These results show potential clinical use of cotargeting IGF-1R and Akt/mTOR in patients with HNSCC.

Cellular bioenergetics is an emerging therapeutic target in cancer. Despite the Warburg effect playing a critical role in providing bioenergetics to tumor cells, inhibition of glycolysis alone showed limited efficacy in clinical trials. Cheong and colleagues show that activation of AMPK as a consequence of decreased glycolysis increases transcription of...

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