Evaluating the current status of protein kinase C (PKC)-protein kinase D (PKD) signalling axis as a novel therapeutic target in ovarian cancer.

Ovarian cancer, especially high grade serous ovarian cancer is one of the most lethal gynaecological malignancies with high relapse rate and patient death. Notwithstanding development of several targeted treatment and immunotherapeutic approaches, researchers fail to turn ovarian cancer into a manageable disease. Protein kinase C (PKC) and protein kinase D (PKD) are families of evolutionarily conserved serine/threonine kinases that can be activated by a plethora of extracellular stimuli such as hormones, growth factors and G-protein coupled receptor agonists. Recent literature suggests that a signalling cascade initiated by these two protein kinases regulates a battery of cellular and physiological processes involved in tumorigenesis including cell proliferation, migration, invasion and angiogenesis. In an urgent need to discover novel therapeutic interventions against a deadly pathology like ovarian cancer, we have discussed the status quo of PKC/PKD signalling axis in context of this disease. Additionally, apart from discussing the structural properties and activation mechanisms of PKC/PKD, we have provided a comprehensive review of the recent reports on tumor promoting functions of PKC isoforms and discussed the potential of PKC/PKD signalling axis as a novel target in this lethal pathology. Furthermore, in this review, we have discussed the significance of several recent clinical trials and development of small molecule inhibitors that target PKC/PKD signalling axis in ovarian cancer.