RO4929097 + erlotinib

RO4929097 + erlotinib is an investigational treatment that has been studied primarily for non-small cell lung cancer (NSCLC). This combination pairs two distinct mechanisms of action to potentially overcome resistance to erlotinib therapy. RO4929097 is a gamma secretase inhibitor that works by preventing the cleavage of Notch to its active form, thereby inhibiting Notch signaling. The Notch pathway plays a key role in maintaining stem cell viability and in epithelial-mesenchymal transition (EMT), processes that may contribute to resistance to erlotinib. Erlotinib (also known by the brand name Tarceva) is an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor used in the treatment of non-small cell lung cancer. All NSCLC patients treated with erlotinib eventually develop resistance, which is why combination approaches have been investigated. The combination was designed to combat the inevitable resistance to erlotinib monotherapy by targeting both the EGFR pathway (via erlotinib) and the Notch pathway (via RO4929097), which may be involved in maintaining cancer stem cells and promoting EMT, both of which contribute to drug resistance.