Methods and compositions for modulating the FGF effect on the sensitivity
of malignant and normal cells to anticancer agents are provided. In
particular, methods and compositions for inhibiting FGF-induced
resistance to a broad spectrum of anticancer agents in solid and
soft-tissue tumors, metastatic lesions, leukemia and lymphoma are
provided. Preferably, the compositions include at least one FGF inhibitor
in combination with a cytotoxic agents, e.g., antimicrotubule agents,
topoisomerase I inhibitors, topoisomerase II inhibitors, antimetabolites,
mitotic inhibitors, alkylating agents, intercalating agents, agents
capable of interfering with a signal transduction pathway (e.g., g., a
protein kinase C inhibitor, e.g., an anti-hormone, e.g., an antibody
against growth factor receptors), an agent that promotes apoptosis and/or
necrosis, an interferon, an interleukin, a tumor necrosis factor, and
radiation.In other embodiments, methods and composition for protecting a
cell in a subject, from one or more of killing, inhibition of growth or
division or other damage caused, e.g., by a cytotoxic agent, are
provided. Preferably, the method includes: administering, to the subject,
an effective amount of at least one FGF agonist, thereby treating the
cell, e.g., protecting or reducing the damage to the dividing cell from
said cytotoxic agent.