44 results about "Topoisomerase-II Inhibitor" patented technology

The administration of cytotoxic agents followed by the administration of heat shock protein 90 inhibitors, such as ansamycins, has a synergistic effect on the growth inhibition of cells. This synergy occurs at doses of each cytotoxic agent that normally only causes minimal growth inhibition of cells. Such combination therapy thus allows one to use lower doses of cytotoxic agents to avoid or reduce their respective toxicity to patients without compromising their growth inhibitory effects. Thus, these combinations can be used for the treatment of an animal, preferably a mammal, that has a cell proliferative disorder, whether the cells have wild-type Rb or are Rb deficient or Rb negative. One such method, directed to treating cell proliferative disorders includes the step of administering a therapeutic effective amount of a cytotoxic agent followed by administering a therapeutic effective amount of a heat shock protein 90 inhibitor. The cytotoxic agent may be a microtubule-affecting agent, topoisomerase II inhibitor, a platinum complex, paclitaxel, or a paclitaxel derivative. The HSP90 inhibitor may be an ansamycin, radicicol or a synthetic compound that binds to the ATP-binding site of HSP90.

Maleimide and succinimide derivatives were found to be effective topoisomerase II catalytic inhibitors. Due to this property, the maleimide and succinimide derivatives were investigated for their use as cytostatic agents and thus in the treatment of cancer. The compounds of the invention can be used in combination treatments with other cytostatic agents, such as topoisomerase II poisons. The maleimide and succinimide derivatives, due to their effective topoisomerase II catalytic inhibitory activity, are also useful as extravasation agents, such as upon administration of a topoisomerase II poison.

This invention is in the area of improved therapeutic combinations for and methods of treating selected retinoblastoma (Rb)-negative cancers and Rb-negative abnormal cellular proliferative disorders using particular topoisomerase inhibitors and specific cyclin-dependent kinase 4 / 6 (CDK4 / 6) inhibitors. In one aspect, the improved treatment of select Rb-negative cancers is disclosed using specific compounds disclosed herein in combination with a topoisomerase I inhibitor.

A combination therapy for treating patients suffering from proliferative diseases or diseases associated with persistent angiogenesis is disclosed. The patient is treated with a camptothecin derivative and one or more chemotherapeutic agents selected from a microtubule active agent; an alkylating agent; an anti-neoplastic anti-metabolite; a platin compound; a topoisomerase II inhibitor; a VEGF inhibitor; a tyrosine kinase inhibitor; an EGFR kinase inhibitor; an mTOR kinase inhibitor; an insulin-like growth factor I inhibitor; a Raf kinase inhibitor; a monoclonal antibody; a proteasome inhibitor; a HDAC inhibitor; and ionizing radiation.

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.

Topoisomerase II alpha (topo IIα) is exported from the cell nucleus in human myeloma cells by a chromosome-maintenance protein-1 (CRM1)-dependent mechanism, resulting in topo II inhibitor resistance. The nuclear export signal (NES) of topo IIα is unique, making it a potential target for small molecule inhibitors. Small molecules NES inhibitors were identified, which inhibited binding of topo IIα to the export receptor CRM1. Inhibition was specific to topo IIα as p53 trafficking was unaffected along with topo IIα protein expression and function (decatenation). These topo IIα-specific nuclear export inhibitors may potentially lead to a new approach in circumventing drug resistance in multiple myeloma. The compounds provide a protocol for treating multiple myeloma or an oncogenic disease. Further, the topoisomerase II nuclear export signal inhibitor may be combined with a topoisomerase II inhibitor.

The present invention relates to certain purines, which act as topoisomerase II catalytic inhibitors. These compounds are useful in combination with topoisomerase II poisons, such as anthracyclines and epipodophyllotoxins, in the treatment of proliferative conditions (e.g., cancer). These compounds are useful in the treatment of tissue damage associated with extravasation of a topoisomerase II poison, such as an anthracycline or an epipodophyllotoxin.