sc-236 and Neoplasms

Angiogenesis is known to be a critical process for the tumor growth and metastasis. There are many indigenous role-players in tumor angiogenesis and anti-angiogenesis, where tumor-host interaction may work. A lot of agents with anti-angiogenic activity have been developed for anti-cancer treatment. Several agents including Marimastat, Primostat, Neovastat, Bay-12-9566m, Interferon-alpha, SU101, retinoids, and IM862, are/were under phase-three study. There are still many future-promising results of basic or clinical studies on inhibitors of MMPs, and inhibitors of VEGF/R, Endostatin, somatostatin analogues, COX-2 inhibitors, and others. Most of the combination treatments of antiangiogenetic agent and conventional anticancer agents therapy, or radiation therapy as we reported, showed relatively small or minute increase in toxicity of these cytotoxic treatments.

Topics: Angiogenesis Inhibitors; Animals; Antineoplastic Agents; Combined Modality Therapy; Cyclooxygenase Inhibitors; Endothelial Growth Factors; Humans; Lymphokines; Matrix Metalloproteinase Inhibitors; Matrix Metalloproteinases; Neoplasms; Neovascularization, Pathologic; Pyrazoles; Radiotherapy; Sulfonamides; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors

Cyclooxygenase-2 (COX-2) is an enzyme expressed primarily in pathologic states, such as inflammatory disorders and cancer, where it mediates prostaglandin production. Its overexpression is associated with more aggressive biologic tumor behavior and adverse patient outcome. Increasing evidence shows that agents that selectively inhibit COX-2 enhance tumor response to radiation or chemotherapeutic agents. This article gives an overview of some of this evidence. In addition, we describe new results showing that celecoxib, a selective COX-2 inhibitor, enhanced response of A431 human tumor xenografts in nude mice to radiation by an enhancement factor (EF) of 1.43 and to the chemotherapeutic agent docetaxel by an EF of 2.07. Celecoxib also enhanced tumor response when added to the combined docetaxel plus radiation treatment (EF = 2.13). Further experiments showed that selective COX-2 inhibitors enhanced tumor cell sensitivity to ionizing radiation, involving inhibition of cellular repair from radiation damage and cell cycle redistribution as mechanisms for some cell types. The results show that selective COX-2 inhibitors have the potential to improve tumor radiotherapy or radiochemotherapy, and this therapeutic strategy is currently under clinical testing.

Topics: Animals; Celecoxib; Combined Modality Therapy; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors; Drug Interactions; Humans; Isoenzymes; Membrane Proteins; Mice; Mice, Inbred C3H; Mice, Nude; Neoplasm Proteins; Neoplasms; Prostaglandin-Endoperoxide Synthases; Pyrazoles; Radiation Tolerance; Radiation-Sensitizing Agents; Sulfonamides