31 results about "Insulin-like growth factor 1 receptor" patented technology

Antibodies against insulin like growth factor I receptor (IGF-IR), methods for their production, pharmaceutical compositions containing said antibodies, and uses for such antibodies are disclosed. Such antibodies are implicated in antitumor therapy.

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 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 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.

Antibodies which bind to IGF-IR and inhibit the binding of IGF-I and IGF-II to IGF-IR are characterized. These antibodies are implicated in anti-tumor therapy.

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 invention refers to new compounds, e.g. podophyllotoxin derivatives, as well as to the use thereof and of known compounds as specific inhibitors of the insulin-like growth factor-1 receptor (IGF-1R). Said compounds can be used for treatment of IGF-1 / IGF-1R dependent diseases, such as cancer, psoriasis, arteriosclerosis, certain endocrine and metabolic disorders etc.

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 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 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.

The present invention relates to insulin-like growth factor 1 receptor binding peptides, polynucleotides encoding them, and methods of making and using the foregoing.

The present disclosure relates to compositions and methods for treating cancers using antisense (AS) nucleic acids directed against Insulin-like Growth Factor 1 Receptor (IGF-1R). The AS may be administered to the patients systemically, or may be used to produce an autologous cancer cell vaccine. In embodiments, the AS are provided in an implantable irradiated biodiffusion chamber comprising tumor cells and an effective amount of the AS. The chambers are irradiated and implanted in the abdomen of subjects and stimulate an immune response that attacks tumors distally. The compositions and methods disclosed herein may be used to treat many different kinds of cancer, for example glioblastoma.

The blood-brain barrier (BBB) prevents transport of molecules larger than 500 Dal tons from blood to brain. Receptor-mediated transcytosis (RMT) facilitates transport across the BBB of specific molecules that bind receptors on brain endothelial cells that form the BBB. An insulin-like growth factor 1 receptor (IGF 1R)-binding antibody or fragment thereof is identified that transmigrates the BBB by RMT. The antibody or fragment is used to deliver a cargo molecule across the BBB, wherein the cargo molecule may be a therapeutic or detectable agent. The antibody is a camelid VHH, prepared by immunizing a llama with a 933-amino acid IGF 1R polypeptide. Humanized forms of the camelid VHH are also generated.

The invention relates to an application of a 5-substituted-2,4-thiazolidinedione compound as shown in general formula (I) disclosed in the specification or pharmaceutically acceptable salts thereof in the preparation of IGF1R (insulin-like growth factor 1 receptor) function regulating medicaments. The 5-substituted-2,4-thiazolidinedione compound has a better effect in the aspect of inhibiting IGF1R kinase activity, and the IGF1R plays an important role in promoting the proliferation and differentiation of tumor cells, so that the compound provided by the invention can be used for preparing the medicaments for treating tumor diseases.

The blood-brain barrier (BBB) prevents transport of molecules larger than 500 Dal tons from blood to brain. Receptor-mediated transcytosis (RMT) facilitates transport across the BBB of specific molecules that bind receptors on brain endothelial cells that form the BBB. An insulin-like growth factor 1 receptor (IGF 1R)-binding antibody or fragment thereof is identified that transmigrates the BBB by RMT. The antibody or fragment is used to deliver a cargo molecule across the BBB, wherein the cargo molecule may be a therapeutic or detectable agent. The antibody is a camelid VHH, prepared by immunizing a llama with a 933-amino acid IGF 1R polypeptide. Humanized forms of the camelid VHH are also generated.

The invention belongs to the field of cytobiology, and discloses a method for separating or identifying lung adenocarcinoma stem cells (group) from lung adenocarcinoma cells (group); the invention also discloses a reagent and a kit for separating or identifying lung adenocarcinoma stem cells (group). The invention shows that the lung adenocarcinoma stem cells have special mark CD24 and insulin-like growth factor-1 receptor (IGF-1R) for the first time, and provides efficient path for separating or identifying lung adenocarcinoma stem cells (group).

The blood-brain barrier (BBB) prevents transport of molecules larger than 500 Daltons from blood to brain. Receptor-mediated transcytosis (RMT) facilitates transport across the BBB of specific molecules that bind receptors on brain endothelial cells that form the BBB. An insulin-like growth factor 1 receptor (IGF1R)-binding antibody or fragment thereof is identified that transmigrates the BBB by RMT. The antibody or fragment is used to deliver a cargo molecule across the BBB, wherein the cargo molecule may be a therapeutic or detectable agent. The antibody is a camelid VHH, prepared by immunizing a llama with a 933-amino acid IGF1R polypeptide. Humanized forms of the camelid VHH are also generated.

The blood-brain barrier (BBB) prevents transport of molecules larger than 500 Dal tons from blood to brain. Receptor-mediated transcytosis (RMT) facilitates transport across the BBB of specific molecules that bind receptors on brain endothelial cells that form the BBB. An insulin-like growth factor 1 receptor (IGF 1R)-binding antibody or fragment thereof is identified that transmigrates the BBB by RMT. The antibody or fragment is used to deliver a cargo molecule across the BBB, wherein the cargo molecule may be a therapeutic or detectable agent. The antibody is a camelid VHH, prepared by immunizing a llama with a 933-amino acid IGF 1R polypeptide. Humanized forms of the camelid VHH are also generated.

The invention relates to pyrazolopyridine derivatives with the structure of formula (I) or pharmaceutically acceptable salts and application of the pyrazolopyridine derivatives or pharmaceutically acceptable salts. The invention also relates to a method for preparing compounds and an intermediate of the compounds.

The present invention is based on our work with E-cadherin, including soluble portions of this integral membrane glycoprotein. The compositions of the present invention include therapeutically effective amounts of a first agent that targets epitopes within one or more of the EC2-EC5 subdomains of the ectodomain of E-cadherin (induing these domains in the shed sEcad fragment) and a second agent that inhibits one or more of: endothelial tube formation; angiogenesis; the human epidermal growth factor receptor family (i.e. HER1-4); an insulin-like growth factor 1 receptor (IGF-1R); any other receptor tyrosine kinase receptor family member; the P13K-MAPK pathway; and the P13K / Akt / mTOR pathway. The compositions can be used in the treatment of epithelial cancers, and may effectively inhibit cellular proliferation, migration, and / or invasiveness. Thus, the present compositions can be used to inhibit tumor growth and metastasis. The present compositions can be used in the treatment of "triple negative" breast cancer patients (in whom breast cancer cells test negative for estrogen receptors, progesterone receptors, and HER2), as well as HER2 -positive and other HER2 -negative tumors. In addition to therapeutic and prophylactic treatment methods, the invention features methods in which cancer is staged depending on the relative amounts of full-length (FL) E-cadherin and soluble E-cadherin (sEcad) and / or with another predictive biomarker for cancer. The greater the amount of sEcad relative to the amount of FL E-cadherin, the more advanced the cancer.

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.

The present invention relates to a pharmaceutical combination comprising an alpha-isoform specific phosphatidylinositol 3-kinase inhibitor compound, such as (S)-Pyrrolidine-1,2-dicarboxylic acid 2-amide 1-({4-methyl-5-[2-(2,2,2-trifluoro-1,1-dimethyl-ethyl)-pyridin-4-yl]-thiazol-2-yl}-amide), or pharmaceutically acceptable salt thereof, and an insulin-like growth factor-1 receptor (IGF1R) inhibitor (e.g., the IGF1R inhibitor ANTIBODY A, or a variant or derivative thereof), a pharmaceutical composition comprising such combination, methods for treating cancer comprising administration of therapeutically effective amounts of such inhibitors to a subject in need thereof, and uses of such combination for the treatment of cancer.

The blood-brain barrier (BBB) prevents transport of molecules larger than 500 Dal tons from blood to brain. Receptor-mediated transcytosis (RMT) facilitates transport across the BBB of specific molecules that bind receptors on brain endothelial cells that form the BBB. An insulin-like growth factor 1 receptor (IGF 1R)-binding antibody or fragment thereof is identified that transmigrates the BBB by RMT. The antibody or fragment is used to deliver a cargo molecule across the BBB, wherein the cargo molecule may be a therapeutic or detectable agent. The antibody is a camelid VHH, prepared by immunizing a llama with a 933-amino acid IGF 1R polypeptide. Humanized forms of the camelid VHH are also generated.

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 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.

The present invention relates to insulin-like growth factor 1 receptor binding peptides, polynucleotides encoding them, and methods of making and using the foregoing.