Table-3:

Article highlights box:

• Preclinical:

• Preclinical studies demonstrated efficacy of everolimus as a mono-therapy. Combinations with agents targeting the EGFR, MEK, RAF/MAPK, CDK4/6 and chemotherapy have shown promise in mouse stu-dies.

• Everolimus plus trametinib demonstrated efficacy in xenograft models (EMC519 PDX).

• Gemcitabine resistant pancreatic cancer cell lines were sensitive to everolimus (MIAPaCa-M).

• Early Clinical:

• Early Clinical Trials investigating the efficacy of everolimus alone or combined with capecitabine, cetuximab, gemcitabine, cisplatin, sora-fenib, and trametinib failed to demonstrate efficacy and was toxic to patients.

• Potential Combined Targets:

• BET, HGF/c-MET, CTGF, Rho-kinase inhibitors other stroma targeted agents.