This invention may be used for the treatment of cellular proliferative disorders including cancer.
Improved cancer treatments are desperately needed for clinical use. Unfortunately, the complex signaling network that preserves genomic integrity, activated in response to DNA damage, is not fully understood. Cells either arrest the cell cycle to preform DNA repair or, instead, undergo apoptosis if DNA damage is great. This invention is a method of treating p53 deficient tumors.
MAPKAP Kinase-2 (MK2) is critical for the activation of G1, S-phase and G2/M checkpoints after exposure to chemotherapeutic agents. Inhibition of MAPKAP Kinase-2 significantly increases the anti-proliferative and cytotoxic effects of cisplatin and doxorubucin on p53 deficient tumor cells. p53 is a tumor suppressor that arrests a cell in G1 or leads to apoptosis. Most tumors have a disrupted p53 pathway allowing MAPKAP Kinase-2 inhibition to selectively target malignancies without affecting normal, healthy cells. This invention includes discovered MAPKAP kinase-2 inhibitors, pharmaceutical compounds containing such inhibitors, and screening methods for identifying additional inhibitors.
- Broad tumor-specific chemosensitization therapy
Healthy cells are unaffected by treatment