Addicted to secrete – novel concepts and targets in cancer therapy

• The secretory pathway is instrumental to oncogenesis and tumor growth.
• The secretory pathway mediates the adaptation of tumor cells to intrinsic and extrinsic demands.
• The secretory pathway conditions the interaction of tumor cells with the extracellular matrix and immune systems.
• The secretory pathway might represent a relevant therapeutic target in cancer.

The unfolded protein response (UPR) mediates the adaptation of the secretory pathway (SP) to fluctuations in cellular protein demand or to environmental variations. Recently, drug screenings have confirmed the therapeutic potential of targeting the UPR in cancer models. However, the UPR may not be the only druggable target of the SP. Moreover, recent studies have revealed other contributions of the SP to cancer development. This article does not intend to describe the well-established implication of UPR signaling pathways in cancer cell life and cell decision, but rather aims at defining the concept of ‘tumor cell secretory addiction’, from molecular, cellular, and therapeutic perspectives. Furthermore, the implication of UPR modulations in this context will be discussed.