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, and
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.