e13526 Background: We have previously described that ABTL0812 has oral anticancer properties. The action is exerted through a mechanism of action involving the inhibition of mTORC1 and mTORC2 (mammalian target of rapamycin) pathways and dihydrofolate reductase (DHFR) expression. Administration of ABTL0812 reduced tumor volume similarly or more than standards of care (SOC) in A549 or MiaPaca2 xenografts in mice. Moreover, a 28-day rat toxicity study has shown very low toxicity (NOAEL=500 mg/Kg) good bioavailability and pharmacokinetic linearity, suggesting a broad therapeutic window. A FiM phase I clinical trial in patients with advanced cancer is scheduled to start in June 2013. Methods: Cellular assays were performed in A549 lung adenocarcinoma, and MiaPaca-2 pancreatic carcinoma cells. Cell proliferation was carried out by bromodeoxyuridine (BrdU) incorporation, cell viability by MTT, and protein expression and phosphorylation by immunoblotting. Cellular apoptosis was assessed both by caspase 3 immunoblot and Hoechst 3342 nuclear staining and quantification of nuclei; and autophagy by LC3-II lipidation assay in immunoblots. All studies were performed with ABTL0812 either alone or in combination with SOC. Results: ABTL0812 potentiated the cytotoxic effects of gemcitabine and docetaxel in MiaPaCa-2 and A549 cancer cells, respectively. In MTT assays, the IC50’s of gemcitabine and docetaxel decreased 7 and 80 times in MiaPaca-2 and A549 cells, respectively, when cells were co-incubated with non-cytotoxic ABTL0812 concentrations. Analysis of the activity (Chou and Talalay’s method) revealed that ABTL0812 synergizes with gemcitabine and docetaxel to promote cytotoxicity. We also present data showing the effects of gemcitabine and docetaxel on the molecular targets of ABTL0812 such as Akt and ribosomal S6 phosphorylation, DHFR expression and cellular autophagy. Conversely, we also show the effects of ABTL0182 on cellular apoptosis induced by gemcitabine and docetaxel. Conclusions: ABTL0812 synergistically potentiates the cytotoxic effect of gemcitabine and docetaxel in pancreatic and lung cancer cell models.