Proline-directed protein kinase FA as a new signal transducing target for lethal cancer treatment.

Proline-directed protein kinase F(A) (PDPK F(A)) has been established as a multisubstrate/multifunctional PDPK essential for the development of highly malignant phenotypes and rapid progression of lethal cancers. The recent immunohistochemical, immunocytochemical and clinicopathologic studies combined demonstrate that overexpressed PDPK F(A) is dynamically and closely associated with the most aggressive malignant cells disseminating from primary tumors to peripheral blood, ascites, pleural effusions and second metastatic tumors of various types of cancer patients with poor prognosis. The antisense gene therapeutic studies further demonstrate that overexpressed PDPK F(A) is essential for the development of all aspects of neoplasia including highly metastatic spread, peritoneal dissemination, splenomegaly and chemoradioresistances. The inhibition of cancer progression together with the simultaneous enhancement of chemoradiosensitivities through the suppression of overexpressed PDPK F(A) by specific drug design may work synergistically with surgery and chemoradiotherapy to improve the poor survival rate and life quality of the patients with lethal malignancies. PDPK F(A), therefore, may represent the heel of Achilles and a new promising target for the strategic development of more efficacious treatment for lethal cancers