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Drug Development
PharmaGap’s Target: Protein Kinase C
PKC is a family of calcium and lipid-activated serine-threonine protein kinases which play a central role in intracellular signal transduction. PKC isoforms plays a key role in cell replication and differentiation, as well as a key regulatory role at various checkpoints in the cell cycle.
Interest in PKC isoforms and their role in cancer were elevated after the discovery in the late 1980s that PKC is a receptor for tumor-promoting phorbol esters. PKC is implicated in many types and stages of cancer, including the chemotherapy-resistant cancer phenotype (multi-drug resistance, or MDR). With MDR, cancer cells effectively become immune to chemotherapy over time. MDR is the major cause of chemotherapy failure and manifests itself in all types of cancer. Approximately 500,000 new cases of MDR cancer are expected to develop in the U.S. alone every year.
PKCalpha and Cancer
In healthy tissue, PKC isoforms are widely expressed in normal levels and are necessary and important signaling molecules. However, aberrant over-expression of PKC occurs in many types and stages of cancer, including non-small cell lung cancer, ovarian, breast, colon, certain leukemia’s, neuroblastoma, prostate, non-Hodgkin’s lymphoma, bladder and pancreatic cancer. In cancer, over-expression of PKC is implicated in malignant transformation and proliferation, faulty apoptosis (cells become effectively immortalized), increased cell migration and cell activation, and desensitizing tumor cells to chemotherapeutic agents (MDR). Numerous independent studies worldwide have validated PKC as a potential target for cancer therapeutics.
PharmaGap’s Lead Drug Targets PKC
The Company’s lead drug candidate, PhGα1, targets and inhibits the activity of PKC in cancer cells. This novel drug is representative of a new class of targeted therapeutics now in development by the pharmaceutical industry that are designed to specifically target molecular defects within a cancer cell, rather than killing cancer cells in general via traditional toxic chemotherapeutics.
