Our demonstration that SMAPs upregulate and activate 4E-BP1 in cancer cells in vivo, and that they can increase 4E-BP1 function in the presence of ERK and mTOR inhibitors, highlights the potential of PP2A-based therapeutics for overcoming resistance to targeted agents that rely on suppression of eIF4F for antitumor activity. The gene discussed is MTOR; the disease is cancer.