95 results about "Enzyme Inhibitor Therapy" patented technology

The present invention provides diagnostic and prognostic methods for predicting the effectiveness of treatment of a cancer patient with an EGFR kinase inhibitor. Methods are provided for predicting the sensitivity of tumor cell growth to inhibition by an EGFR kinase inhibitor, comprising assessing whether the tumor cell has undergone an epithelial to mesenchymal transition (EMT), by determining the expression level of epithelial and / or mesenchymal biomarkers, wherein tumor cells that have undergone an EMT are substantially less sensitive to inhibition by EGFR kinase inhibitors. Improved methods for treating cancer patients with EGFR kinase inhibitors that incorporate the above methodology are also provided. Additionally, methods are provided for the identification of new biomarkers that are predictive of responsiveness of tumors to EGFR kinase inhibitors. Furthermore, methods for the identification of agents that restore the sensitivity of tumor cells that have undergone EMT to inhibition by EGFR kinase inhibitors are also provided.

The present invention provides diagnostic and prognostic methods for predicting the effectiveness of treatment of a cancer patient with an EGFR kinase inhibitor. Methods are provided for predicting the sensitivity of tumor cell growth to inhibition by an EGFR kinase inhibitor, comprising assessing whether the tumor cell has undergone an epithelial to mesenchymal transition (EMT), by determining the expression level of epithelial and / or mesenchymal biomarkers, wherein tumor cells that have undergone an EMT are substantially less sensitive to inhibition by EGFR kinase inhibitors. Improved methods for treating cancer patients with EGFR kinase inhibitors that incorporate the above methodology are also provided. Additionally, methods are provided for the identification of new biomarkers that are predictive of responsiveness of tumors to EGFR kinase inhibitors. Furthermore, methods for the identification of agents that restore the sensitivity of tumor cells that have undergone EMT to inhibition by EGFR kinase inhibitors are also provided.

The present invention provides a method for treating cancer. The method involves the administration of an HSP90 inhibitor and an enzyme inhibitor, where the combined administration provides a synergistic effect. In one aspect of the invention, a method of treating cancer is provided where a subject is treated with a dose of an HSP90 inhibitor in one step and a dose of an enzyme inhibitor in another step. In another aspect of the invention, a method of treating cancer is provided where a subject is first treated with a dose of an HSP90 inhibitor and subsequently treated with a dose of an enzyme inhibitor. In another aspect of the invention, a method of treating cancer is provided where a subject is first treated with a dose of an enzyme inhibitor and subsequently treated with a dose of an HSP90 inhibitor.

Glucosylceramide synthase inhibitors and compositions containing the same are disclosed. Methods of using the glucosylceramide synthase inhibitors in the treatment of diseases and conditions wherein inhibition of glucosylceramide synthase provides a benefit, like Gaucher disease and Fabry disease, also are disclosed.

The present invention provides diagnostic methods for predicting the effectiveness of treatment of an ovarian cancer patient with an IGF-1R kinase inhibitor. Methods are provided for predicting the sensitivity of tumor cell growth to inhibition by an IGF-1R kinase inhibitor, comprising assessing whether the tumor cells possess mutant K-RAS. The present invention thus provides a method of identifying patients with ovarian cancer who are most likely to benefit from treatment with an IGF-1R kinase inhibitor. Improved methods for treating cancer patients with IGF-1R kinase inhibitors that incorporate this methodology are also provided. The present invention also provides diagnostic methods for predicting the effectiveness of treatment of cancer patients with IGF-1R kinase inhibitors, based on a determination of the mutation status of the genes K-RAS, B-RAF, PTEN and PIK3CA, which can be used to identify tumor cell types that will be sensitive to IGF-1R kinase inhibitors, and also those that will be insensitive.

The use of various biomarkers to assess a subject's suitability for treatment with a EGFR / ErbB2 kinase inhibitor for a solid tumor are described. The biomarkers include TGFalpha, pS6, IGF-1R and levels of apoptosis occurring in tumor tissue.

The present invention provides diagnostic and prognostic methods for predicting the effectiveness of treatment of a cancer patient with an IGF-1R kinase inhibitor. Methods are provided for predicting the sensitivity of tumor cell growth to inhibition by an IGF-1R kinase inhibitor, comprising assessing whether the tumor cell has undergone an epithelial to mesenchymal transition (EMT), by determining the expression level of epithelial and / or mesenchymal biomarkers, wherein tumor cells that have undergone an EMT are substantially less sensitive to inhibition by IGF-1R kinase inhibitors. Improved methods for treating cancer patients with IGF-1R kinase inhibitors that incorporate the above methodology are also provided. Additionally, methods are provided for the identification of new biomarkers that are predictive of responsiveness of tumors to IGF-1R kinase inhibitors. Furthermore, methods for the identification of agents that restore the sensitivity of tumor cells that have undergone EMT to inhibition by IGF-1R kinase inhibitors are also provided. pErk, HER3 and pHER are also demonstrated to be effective biomarkers for predicting sensitivity of tumor cells to IGF-1R kinase inhibitors.

Compounds of formula (I): in which R1, R2, R3, R4, X, Y and n have the meanings given in the specification, are inhibitors of Trk kinases and are useful in the treatment of diseases which can be treated with a Trk kinase inhibitor. The formula (I) is shown in the description.

The present invention provides diagnostic and prognostic methods for predicting the effectiveness of treatment of a cancer patient with an IGF-1R kinase inhibitor. Methods are provided for predicting the sensitivity of tumor cell growth to inhibition by an IGF-1R kinase inhibitor, comprising assessing whether the tumor cell has undergone an epithelial to mesenchymal transition (EMT), by determining the expression level of epithelial and / or mesenchymal biomarkers, wherein tumor cells that have undergone an EMT are substantially less sensitive to inhibition by IGF-1R kinase inhibitors. Improved methods for treating cancer patients with IGF-1R kinase inhibitors that incorporate the above methodology are also provided. Additionally, methods are provided for the identification of new biomarkers that are predictive of responsiveness of tumors to IGF-1R kinase inhibitors. Furthermore, methods for the identification of agents that restore the sensitivity of tumor cells that have undergone EMT to inhibition by IGF-1R kinase inhibitors are also provided. pErk, HER3 and pHER are also demonstrated to be effective biomarkers for predicting sensitivity of tumor cells to IGF-1R kinase inhibitors.

The present invention provides diagnostic and prognostic methods for predicting the effectiveness of treatment of a cancer patient with inhibitors of EGFR kinase, PDGFR kinase, or FGFR kinase. Based on the surprising discovery that tumors cells after having undergone an EMT, while being mesenchymal-like, still express characteristics of both epithelial and mesenchymal cells, and that such cells have altered sensitivity to inhibition by receptor protein-tyrosine kinase inhibitors, in that they have become relatively insensitive to EGFR kinase inhibitors, but have frequently acquired sensitivity to inhibitors of other receptor protein-tyrosine kinases such as PDGFR or FGFR, methods have been devised for determining levels of specific epithelial and mesenchymal biomarkers that identify such “hybrid” tumor cells (e.g. determination of co-expression of vimentin and epithelial keratins), and thus predict the tumor's likely sensitivity to inhibitors of EGFR kinase, PDGFR kinase, or FGFR kinase. Improved methods for treating cancer patients with EGFR, PDGFR or FGFR kinase inhibitors that incorporate such methodology are also provided.

The present invention provides diagnostic methods for assessing the EMT status of tumor cells, and for predicting the effectiveness of treatment of a cancer patient with an EGFR or IGF-1R kinase inhibitor, utilizing an EMT gene signature index score. The present invention further provides methods for treating patients with cancer that incorporate these methods.

The present invention relates to a novel method for the treatment of neoplasia, including cancer and other diseases and conditions in humans and mammals. More particularly, in preferred aspects, the present invention provides a method for the use of prenylcysteine analogs for the treatment of neoplasia, hyperproliferative cell growth including psoriasis, restenosis following cardiovascular surgery, hyperplasia, including renal hyperplasia, chronic inflammatory diseases including rheumatoid and osteoarthritis, among others.

The reagent, pharmaceutical formulation, kit, and methods of the invention provides a new approach for treating pancreatic cancers. The invention provides the use of Na+e / K+-ATPase inhibitors, such as cardiac glycosides (e.g. ouabain and proscillaridin, etc.), either alone or in combination with other standard therapeutic agents (chemo- or radio-therapies, etc.) for treating pancreatic cancers. The subject Na+ / K+-ATPase inhibitors, such as cardiac glycosides, including bufadieneolides or their corresponding aglycones (e.g., proscillaridin, scillaren, and scillarenin, etc.), especially in oral formulations and / or solid dosage forms containing more than 1 mg of active ingredients.

The present invention provides diagnostic methods for predicting the effectiveness of treatment of a cancer patient with an EGFR kinase inhibitor. These methods are based on the surprising discovery that the effectiveness of treatment with an EGFR kinase inhibitor is predicted by whether a patient's tumor cells express a high or a low level of the biomarkers vimentin and E-cadherin, such that patients whose tumors express a high level of at least one of the biomarkers vimentin and E-cadherin have a longer overall survival and progression free survival than patients whose tumors express a low level of both vimentin and E-cadherin. The present invention further provides a method for treating tumors or tumor metastases in a patient, comprising the steps of diagnosing a patient's likely responsiveness to an EGFR kinase inhibitor by assessing whether tumor cells express a high level of at least one of the biomarkers vimentin and E-cadherin, and administering to said patient a therapeutically effective amount of an EGFR kinase inhibitor (e.g. erlotinib), particularly when effectiveness of the inhibitor is predicted.

A method is described for the prevention and / or treatment of vascular disorders and vascular disorder-related complications in a subject, the method comprising administering to the subject a Cox-2 inhibitor in combination with a cAMP-specific PDE inhibitor. Also described are therapeutic and pharmaceutical compositions and kits that are useful in the present invention.

The reagent, pharmaceutical formulation, kit, and methods of the invention provides a new approach to treat refractory cancers using Na+ / K+-ATPase inhibitors, such as cardiac glycosides, including bufadienolides or their corresponding aglycones (e.g., proscillaridin, scillaren, and scillarenin, etc.), especially in oral formulations and / or solid dosage forms containing more than 1 mg of active ingredients.

The present invention provides diagnostic and prognostic methods for predicting the effectiveness of treatment of a cancer patient with an EGFR kinase inhibitor. Methods are provided for predicting the sensitivity of tumor cell growth to inhibition by an EGFR kinase inhibitor, comprising assessing whether the tumor cell has undergone an epithelial to mesenchymal transition (EMT), by determining the expression level of epithelial and / or mesenchymal biomarkers, wherein tumor cells that have undergone an EMT are substantially less sensitive to inhibition by EGFR kinase inhibitors. Improved methods for treating cancer patients with EGFR kinase inhibitors that incorporate the above methodology are also provided. Additionally, methods are provided for the identification of new biomarkers that are predictive of responsiveness of tumors to EGFR kinase inhibitors. Furthermore, methods for the identification of agents that restore the sensitivity of tumor cells that have undergone EMT to inhibition by EGFR kinase inhibitors are also provided.

The present invention provides diagnostic methods for predicting the effectiveness of treatment of a cancer patient with an IGF-1R kinase inhibitor. Methods are provided for predicting the sensitivity of tumor cell growth to inhibition by an IGF-1R kinase inhibitor, comprising assessing whether the tumor cell expresses certain sensitivity or resistance biomarkers, or genomic classifiers. Improved methods for treating cancer patients with IGF-1R kinase inhibitors that incorporate this methodology are also provided.

The present invention provides diagnostic methods for predicting the effectiveness of treatment of a cancer patient with an IGF-1R kinase inhibitor that inhibits both IGF-1R and IR kinases. Methods are provided for identifying patients with cancer who are likely to benefit from treatment with an IGF-1R kinase inhibitor that inhibits both IGF-1R and IR kinases. Methods are also provided for identifying patients with cancer who are likely to benefit from treatment with an IGF-1R kinase inhibitor that inhibits both IGF-1R and IR kinases, but who would likely not respond to therapy with an anti-IGF-1R antibody. Methods are also provided for identifying patients with cancer who are more likely to benefit from treatment with anti-IGF-1R antibody. Improved methods for treating cancer patients with IGF-1R kinase inhibitors that incorporate these methods are also provided.

The disclosure provides methods of treating cognitive disorders by administering a HMG CoA reductase inhibitor. Cognitive deficits treatable with the inhibitor compound include those associated with Angelman Syndrome, Neurofibromatosis-1, certain forms of X-linked mental retardation, tuberous sclerosis, Down Syndrome, autism, and attention deficit / hyperactivity disorder.

A splice variant of bcr-abl mRNA that produces BCR-ABL protein with a truncated C-terminus and its role in resistance to treatment with kinase inhibitors is disclosed. Vectors for expressing the truncated gene product are provided as well as recombinant cells that express the truncated gene product from a cDNA construct. Also provided are methods compositions and kits for detecting the BCR-ABL splice variant. Additionally, methods for screening BCR-ABL kinase domain inhibitors which rely on the recombinant cells and methods of predicting likelihood for resistance of a CML patient with a BCR / ABL translocation respond to treatment with one or more BCR-ABL kinase inhibitors are also disclosed.

The present invention provides diagnostic and prognostic methods for predicting the effectiveness of treatment of a cancer patient with an IGF-1R kinase inhibitor. Methods are provided for predicting the sensitivity of tumor cell growth to inhibition by an IGF-1R kinase inhibitor, comprising assessing whether the tumor cell has undergone an epithelial to mesenchymal transition (EMT), by determining the expression level of epithelial and / or mesenchymal biomarkers, wherein tumor cells that have undergone an EMT are substantially less sensitive to inhibition by IGF-1R kinase inhibitors. Improved methods for treating cancer patients with IGF-1R kinase inhibitors that incorporate the above methodology are also provided. Additionally, methods are provided for the identification of new biomarkers that are predictive of responsiveness of tumors to IGF-1R kinase inhibitors. Furthermore, methods for the identification of agents that restore the sensitivity of tumor cells that have undergone EMT to inhibition by IGF-1R kinase inhibitors are also provided. pErk, HER3 and pHER are also demonstrated to be effective biomarkers for predicting sensitivity of tumor cells to IGF-1R kinase inhibitors.

A method of treating prostate cancers, including androgen refractory prostate cancers, using glycogen synthase kinase-3β inhibitors, such as lithium.

Methods are provided of treating cancer with one or more farnesyl transferase inhibitors. Methods are provided for identifying cancers that are particularly susceptible to treatment with one or more farneseyl transferase inhibitors by identifying cancers that express low levels of UCH-L1.

The present invention provides diagnostic and prognostic methods for predicting the effectiveness of treatment of a cancer patient with inhibitors of EGFR kinase, PDGFR kinase, or FGFR kinase. Based on the surprising discovery that tumors cells after having undergone an EMT, while being mesenchymal-like, still express characteristics of both epithelial and mesenchymal cells, and that such cells have altered sensitivity to inhibition by receptor protein-tyrosine kinase inhibitors, in that they have become relatively insensitive to EGFR kinase inhibitors, but have frequently acquired sensitivity to inhibitors of other receptor protein-tyrosine kinases such as PDGFR or FGFR, methods have been devised for determining levels of specific epithelial and mesenchymal biomarkers that identify such “hybrid” tumor cells (e.g. determination of co-expression of vimentin and epithelial keratins), and thus predict the tumor's likely sensitivity to inhibitors of EGFR kinase, PDGFR kinase, or FGFR kinase. Improved methods for treating cancer patients with EGFR, PDGFR or FGFR kinase inhibitors that incorporate such methodology are also provided.

The present invention provides diagnostic methods for predicting the effectiveness of treatment of an hepatocellular carcinoma (HCC) patient with an IGF-1R kinase inhibitor by assessing whether the HCC tumor cells express a high level of AFP, or whether serum levels of AFP protein are high. The present invention also provides diagnostic methods for predicting the effectiveness of treatment of cancer patients with IGF-1R kinase inhibitors, based on a determination of the expression level of IR, IGF-2, IGFBP3 or IGFBP7 in tumor cells, or a 4-gene index calculated using the expression vales for each of these four genes, which can be used to identify tumors that will be sensitive to IGF-1R kinase inhibitors, and also those that will be insensitive. Improved methods for treating cancer patients with IGF-1R kinase inhibitors that incorporate the above methods are also provided.

Compounds of Formula (I) or stereoisomers, tautomers, or pharmaceutically acceptable salts, solvates or prodrugs thereof, wherein Ring A, Ring C and X are as defined herein, are inhibitors of TrkA kinase and are useful in the treatment of diseases which can be treated with a TrkA kinase inhibitor such as pain, cancer, inflammation / inflammatory diseases, neurodegenerative diseases, certain infectious diseases, Sjogren's syndrome, endometriosis, diabetic peripheral neuropathy, prostatitis or pelvic pain syndrome.