Phospholipase D inhibitors for targeted cancer therapy: Potentials and limitations

Phospholipase D (PLD) enzyme is considered a critical regulator of numerous aspects of cell biology and signal transduction pathways. Deregulation of the expression and activity of PLDs has been linked to numerous diseases, including cancer. PLD isoforms and their hydrolysate phosphatidic acid are involved in multiple stages of tumorigenesis, angiogenesis, and metastasis. Numerous in vitro and in vivo studies performed thus far highlighted PLD inhibition as a promising therapeutic strategy against cancer. Considerable research efforts have been dedicated to structure-guided inhibitor design and development of specific potent and nontoxic PLD inhibitors, which may impede multiple aspects of cancer growth and invasion by acting either as a single agent or in combination with chemotherapy/radiotherapy. Based on the established knowledge of these subjects, the therapeutic potentials and limitations of PLD inhibitors application in targeted cancer therapy are discussed in this chapter.