1207 results about "Non-small cell lung cancer (NSCLC)" patented technology

The present invention relates to the treatment of EGFR-mediated disease, particularly cancer, which is resistant to tyrosine kinase inhibitor therapies. Methods for treatment of cancer and reduction of tumor growth in individuals with secondary EGFR mutations, particularly tyrosine kinase domain mutations, resistant to standard therapy are provided. The invention provides methods for the treatment of tyrosine kinase inhibitor resistant cancers with anti-EGFR antibodies. Methods for treatment of recurrent lung cancer, including non-small cell lung carcinoma which is resistant to tyrosine kinase inhibitors, with the antibody anti-EGFR mAb806 are described.

Disclosed are methods for detecting non-small cell lung cancer (NSCLC) using differentially expressed genes KIF11, GHSR1b, NTSR1, and FOXM1. Also disclosed are methods of identifying compounds for treating and preventing NSCLC, based on the interaction between KOC1 and KIF11, or NMU and GHSR1b or NTSR1.

The invention provides antibodies to a mutant form of the epidermal growth factor receptor known as EGFRvIII found only or primarily on the surface of glioblastoma cells, and on cells of breast, ovarian and non-small cell lung carcinomas. The antibodies provided by the invention have the complementarity determining regions (“CDRs”) of the scFv designated MR1, but with mutations at positions 98 and 99 in the CDR3 of the heavy chain variable region and, optionally, in other CDRs. In particular, the invention provides an antibody, designated MR1-1, which mutates MR1 in the CDR3 of the VH and VL chains. The invention provides additional antibodies in which MR1 is mutated in the CDR1 and 2 of VH or VL, or both.

Chemotherapeutic treatment for certain cancers may be combined with low intensity, intermediate frequency alternating electric fields that are tuned to a particular type of target cell. When the tuned fields were combined with Paclitaxel, Doxorubicin or Cyclophosphamide, excellent results were obtained against human breast cancer cells (MDA-MB-231) and non-small cell lung (H1299) carcinomas in culture. More specifically, cell proliferation inhibition similar to that obtained by drug alone was reached by exposure to the combined treatment at drug concentrations between one and two orders of magnitude lower than for drug-only regimens of treatment.

An object of the present invention is to provide an enhancing agent for effect of anticancer agent for achieving an excellent therapeutic effect on cancer. The enhancing agent for effect of anticancer agent according to the present invention which is a solving means therefor is characterized in that a nitric oxide donor is an effective ingredient. In accordance with the present invention, an excellent therapeutic effect is able to be achieved on non-small cell lung cancer which is still in such a state that no effective therapeutic method has been established yet for a progressive cancer which is not operable and is one of cancers where chemotherapy is most difficult to apply.

The present invention relates to a composition comprising at least one mRNA encoding a combination of antigens capable of eliciting an (adaptive) immune response in a mammal, wherein the antigens are selected from the group consisting of 5T4 (Trophoblast glycoprotein, TPBG), Survivin (Baculoviral TAP repeat-containing protein 5; BIRC5), NY-ESO-1 (New York esophageal squamous cell carcinoma 1, CTAG1B), MAGE-C1 (Melanoma antigen family C1), MAGE-C2 (Melanoma antigen family C2), and MUC1 (Mucin 1). The invention furthermore relates to a vaccine comprising at least one mRNA encoding such a combination of antigens, and to the use of said composition (for the preparation of a vaccine) and / or of the vaccine for eliciting an (adaptive) immune response for the treatment of lung cancer, preferably of non-small cell lung cancer (NSCLC), and diseases or disorders related thereto. Finally, the invention relates to kits, particularly to kits of parts, containing the composition and / or the vaccine.

The invention discloses a pyrimidoheterocyclic compound represented as the formula (I), or a pharmaceutically acceptable salt or a stereisomer thereof, or a prodrug molecule thereof. The pyrimidoheterocyclic compound can effectively inhibit growth of various tumor cells and has an inhibiting effect on EGFR protease. The pyrimidoheterocyclic compound can be used for preparing an anti-tumor drug, and can overcome drug resistance caused by medicines in the prior art, such as gefitinib, erlotinib and the like, has a selectivity on wild non-small cell lung cancer and is excellent in pharmacokinetic property.

Objective methods for detecting and diagnosing small cell lung cancer (SCLC) are described herein. In one embodiment, the diagnostic method involves determining the expression level of an SCLC-associated gene that discriminates between SCLC cells and normal cells. In another embodiment, the diagnostic method involves determining the expression level of an SCLC-associated gene that distinguishes two major histological types of lung cancer, non-small cell lung cancer (NSCLC) and SCLC. Finally, the present invention provides methods of screening for therapeutic agents useful in the treatment of small cell lung cancer, methods of treating small cell lung cancer and method for vaccinating a subject against small cell lung cancer. Furthermore, the present invention provides chemotherapy resistant lung cancer- or SCLC-associated genes as diagnostic markers and / or molecular targets for therapeutic agent for these cancers. These genes are up-regulated in chemoresistant lung cancer or SCLC. Accordingly, chemoresistant lung cancer or SCLC can be predicted using expression level of the genes as diagnostic markers. As the result, any adverse effects caused by ineffective chemotherapy can be avoided, and more suitable and effective therapeutic strategy can be selected.

Provided is a compound useful as an inhibitor against the kinase activity of EML4-ALK fusion protein.As a result of intensive and extensive studies on compounds having inhibitory activity against the kinase activity of EML4-ALK fusion protein, the present inventors found that the diamino heterocyclic carboxamide compounds of the present invention had inhibitory activity against the kinase activity of EML4-ALK fusion protein. By this finding, the present invention was completed. The compounds of the present invention can be used as a pharmaceutical composition for preventing and / or treating cancer, such as lung cancer, non-small cell lung cancer, and small cell lung cancer.

Chemotherapeutic treatment for certain cancers may be combined with low intensity, intermediate frequency alternating electric fields that are tuned to a particular type of target cell. When the tuned fields were combined with Paclitaxel, Doxorubicin or Cyclophosphamide, excellent results were obtained against human breast cancer cells (MDA-MB-231) and non-small cell lung (H1299) carcinomas in culture. More specifically, cell proliferation inhibition similar to that obtained by drug alone was reached by exposure to the combined treatment at drug concentrations between one and two orders of magnitude lower than for drug-only regimens of treatment.

The present invention relates to L genes and gene products that are differentially expressed in cancer tissues and cell lines. In a particular aspect of the invention, L genes and gene products are differentially expressed in lung cancer tissues and cell lines. In accordance with the present invention, L nucleic acid sequences, amino acid sequences and antibodies thereto, and methods of use thereof are presented. The L molecules and methods of the invention may be used to monitor expression levels of L genes, wherein the detection of aberrant levels of L molecules provides a positive diagnostic indicator of lung cancer and / or other L gene associated cancers and a useful prognostic indice of the state of such diseases. Also provided are compounds capable of modulating an L molecule mediated activity, which are identified using the L molecules and methods of the invention. Such L molecule modulating compounds may be used efficaciously to treat patients with lung cancer, or other L antigen positive cancers.

A cancer testis antigen biomarker useful to determine whether a non- small cell lung cancer tumor is likely to respond to neoadjuvant chemotherapy is provided. Methods of using the biomarker in the diagnosis, treatment and prognosis of non-small cell lung cancer also are provided.

The present invention relates to novel kinase inhibitors and modulator compounds useful for the treatment of various diseases. More particularly, the invention is concerned with such compounds, kinase / compound adducts, methods of treating diseases, and methods of synthesis of the compounds. Preferrably, the compounds are useful for the modulation of kinase activity of Raf kinases and disease polymorphs thereof. Compounds of the present invention find utility in the treatment of mammalian cancers and especially human cancers including but not limited to malignant melanoma, colorectal cancer, ovarian cancer, papillary thyroid carcinoma, non small cell lung cancer, and mesothelioma. Compounds of the present invention also find utility in the treatment of rheumatoid arthritis and retinopathies including diabetic retinal neuropathy and macular degeneration.

Methods are provided for the detection of and determining prognosis of metastatic breast, lung, prostate, and / or pancreatic cancer using various genetic markers, including markers for gene clusters linked by Esx. In one method, breast cancer micrometastases and non-small cell lung cancer metastases or micrometastases are detected in a patient by determining whether the AGR2 or TFF1 genes are overexpressed in a cell sample compared to control lymph node tissue cells. In a further method, the likelihood that a patient diagnosed with breast cancer will respond to hormonal therapy is predicted by determining a higher expression level of the AGR2 gene compared to a control gene. In a further method, a decreased probability of survival for a patient diagnosed with early stage non-small cell lung cancer is predicted by determining a higher expression level of the AGR2 gene compared to a control gene. Kits for practicing the methods of the invention are further provided. Methods are also provided for the identification of markers for which overexpression is indicative of the presence of micrometastatic disease.

Methods using mass spectral data analysis and a classification algorithm provide an ability to determine whether a non-small-cell lung cancer (NSCLC) patient is likely to benefit from a monoclonal antibody drug targeting an epidermal growth factor receptor pathway. A mass spectrum is obtained from a sample (e.g. blood sample) from the patient. One or more predefined pre-processing steps are performed on the mass spectrum. Values of selected features in the spectrum at one or more predefined m / z ranges are obtained after the pre-processing steps have been performed. Such values are used in a classification algorithm using a training set comprising class-labeled spectra produced from samples from other patients to identify the patient as being likely to benefit from treatment with the drug.

Provided is pyrazole derivatives as a TNIK (Traf2- and NCK-interacting kinase), IKKε (I-kappa-B kinase epsilon) and TBK1 (TANK-binding kinase 1) inhibitor; the pyrazole derivative according to the present invention effectively inhibits TNIK, IKKε and TBK1, and thus is useful not only as an anticancer agent for the treatment of various cancers including colorectal cancer, breast cancer, CNS cancer, colon cancer, non-small cell lung cancer, kidney cancer, prostate cancer, ovarian cancer, uterus cancer, stomach cancer, liver cancer, skin cancer, lung cancer, brain cancer, bladder cancer, esophageal cancer, pancreatic cancer, thyroid cancer, head and neck cancer, squamous cell carcinoma, osteosarcoma, B-cell or T-cell lymphoma, acute or chronic leukemia and multiple myeloma, but as a therapeutic agent for chronic inflammation.

PCT No. PCT / US97 / 11564 Sec. 371 Date Apr. 14, 1999 Sec. 102(e) Date Apr. 14, 1999 PCT Filed Jul. 8, 1997 PCT Pub. No. WO98 / 01132 PCT Pub. Date Jan. 15, 1998The present invention relates to specific adamantyl or adamantyl group derivative containing retinoid compounds induce apoptosis of cancer cells. These adamantyl retinoid derivatives are useful for the treatment of many cancers and solid tumors, especially androgen-independent prostate cancer, skin cancer, pancreatic carcinomas, colon cancer, melanoma, ovarian cancer, liver cancer, small cell lung carcinoma, non-small cell lung carcinoma, cervical carcinoma, brain cancer, bladder cancer, breast cancer, neuroblastoma / glioblastoma, and leukemia. Also, the invention relates to novel adamantyl or adamantyl group derivative compounds which are useful as active agents for the treatment or prevention of keratinization disorders and other dermatological conditions, and other diseases.

Novel compounds for treatment of cancer and disorders associated with angiogenesis function. Also disclosed are a method of preparing the compounds, pharmaceutical compositions and packaged products containing the compounds, a method of using these molecules to treat cancer (e.g., leukemia, non-small cell lung cancer, colon cancer, CNS cancer, melanoma, ovarian cancer, breast cancer, renal cancer, and prostate cancer) and disorders associated with angiogenesis function (e.g., age-related macular degeneration, macular dystrophy, and diabetes), a method of monitoring the treatment, a method of profiling gene expression, and a method of modulating cell growth, cell cycle, apoptosis, or gene expression.

The present invention relates to compounds, small interfering RNAs and compositions and methods of inhibiting tumorigenesis using agents that inhibit the sonic hedgehog and GLI signaling pathway, including agents that inhibit GLI expression, synthesis and / or function. The present invention also relates to particular biomarkers that can be used in the diagnosis and prognosis of cancer. Methods of treating cancer, including glioblastomas, medulloblastomas, basal cell carcinomas, prostate cancer and small cell and non-small cell lung cancer are also provided using small organic compounds, siRNAs and blocking antibodies that inhibit or block the SHH / GLI pathway.

Medical image data is analysed to produce a biomarker. The data is filtered with a plurality of band-pass filters each having a different bandwidth. A texture parameter is then determined from the filtered data from each filter and the biomarker is determined as at a ratio of the texture parameters. When the biomarker is obtained from a CT image of a liver, it can be predictive of poor survival, disease extent and liver physiology of a patient following resection of colorectal cancer. When obtained from a mammographic image, the biomarker can be indicative of cancer invasion and receptor status within mammographic abnormalities. When obtained from a CT image of a lung nodule, the biomarker can be predictive of tumour stage (or grading) and tumour metabolism of a patient with non-small cell lung carcinoma (lung cancer). When obtained from an MRI image of the brain, the biomarker can be indicative of schizophrenia and / or other brain disorders.

The present invention relates to tumor targeting units comprising a peptide sequence X—R—Y—P—Zn, or a pharmaceutically or physiologically acceptable salt thereof. The invention further relates to tumor targeting agents comprising at least one targeting unit according to the present invention, directly or indirectly coupled to at least one effector unit. The present invention further relates to diagnostic or pharmaceutical compositions comprising at least one targeting unit or at least one targeting agent according to the present invention, and to the use of targeting units or targeting agents according to the present invention for the preparation of a medicament for the treatment of cancer or cancer related diseases, especially for the treatment of non-small cell lung cancer or its metastases.

The invention belongs to the field of drug synthesis and in particular relates to a series of novel peptide boric acids as well as an ester compound or pharmaceutical salt thereof, and a preparation method and application of the peptide boric acids as well as the ester compound or pharmaceutical salt thereof in pharmacodynamics. A structure of the peptide boric acid and the ester compound or pharmaceutical salt thereof is shown in a formula I (described in the specification). The compound provided by the invention can be used for preparing a proteasome inhibitor and can further be used for treating solid tumours and blood tumours, wherein the solid tumours are selected from non-small cell lung cancer, small cell lung cancer, lung adenocarcinoma, lung squamous carcinoma, pancreatic cancer, breast cancer, prostate cancer, liver cancer, skin cancer, epithelial cell cancer, gastrointestinal stromal tumor, nasopharynx cancer and leukemia; and the blood tumours are selected from multiple myeloma, mantle cell lymphoma and histiocytic lymphoma.

The present invention identifies and quantifies changes in gene expression associated with non-small cell lung cancer NSCLC by examining gene expression in tissue from normal lung and diseased lung. The present invention also identifies and quantifies expression profiles which serve as useful diagnostic markers as well as markers that are useful to monitor disease states, disease progression, drug toxicity, drug efficacy and drug metabolism.

The invention provides novel compositions, methods and uses, for the diagnosis, prognosis, prediction, prevention and aid in treatment of malignant neoplasia such as breast cancer, ovarian cancer, gastric cancer, colon cancer, esophageal cancer, mesenchymal cancer, bladder cancer or non-small cell lung cancer. Genes that are chromosomally amplified in breast tissue of breast cancer patients are disclosed. Further disclosed are chromosomally amplified genes and non-amplified genes that correlate to Taxane resistance, Taxane benefit or adverse Taxane reaction, which can be used as an aid to make therapy dicisions.

In accordance with the invention, novel gene deletions and translocations involving chromosome 2 resulting in fusion proteins combining part of Anaplastic Lymphoma Kinase (ALK) kinase with part of a secondary protein have now been identified in human solid tumors, e.g. non-small cell lung carcinoma (NSCLC). Secondary proteins include Echinoderm Microtubule-Associated Protein-Like 4 (EML-4) and TRK-Fusion Gene (TFG). The EML4-ALK fusion protein, which retains ALK tyrosine kinase activity, was confirmed to drive the proliferation and survival of NSCLC characterized by this mutation. The invention therefore provides, in part, isolated polynucleotides and vectors encoding the disclosed mutant ALK kinase polypeptides, probes for detecting it, isolated mutant polypeptides, recombinant polypeptides, and reagents for detecting the fusion and truncated polypeptides. The disclosed identification of this new fusion protein enables new methods for determining the presence of these mutant ALK kinase polypeptides in a biological sample, methods for screening for compounds that inhibit the proteins, and methods for inhibiting the progression of a cancer characterized by the mutant polynucleotides or polypeptides, which are also provided by the invention.

The invention provides a detection method for a non-small cell lung cancer peripheral blood circulating tumor cell PDL1 gene. The method comprises the steps that a, a peripheral blood sample from a non-small cell lung cancer is subjected to membrane filtration, and peripheral blood circulating tumor cells are obtained; b, a filter membrane obtained in the step a is fixed; c, the filter membrane obtained in the step b is detected in situ to determine the PDL1 expression condition; if PDL1 monochrome positive cells are detected in the step c, and HE dyeing is further used for identifying circulating tumor cells for the filter membrane.

This invention relates to the identification and treatment of aggressive lung cancer tumors in patients. More particularly, it provides a method of identifying patients with non-small cell lung carcinoma (NSCLC) who have an aggressive node-negative (N0) tumor and a likelihood of a poor overall survival. The method comprises the step of determining if one or more of certain identified proteins are activated in tumor cells obtained from the patient's tumor, wherein the activation of one or more of the proteins indicates that the patient has an aggressive N0 tumor and is likely to have a poor overall-survival. The invention also provides a method for selecting a treatment for an NSCLC patient with an N0 tumor and a method for treating such patients. It further provides a kit for identifying an NSCLC patient with an aggressive N0 tumor and a likelihood of a poor overall survival and a pharmaceutical composition for treating such patients.

Disclosed are novel calcium release-activated calcium (CRAC) channel inhibitors, methods for preparing them, pharmaceutical compositions containing them, and methods of treatment using them. The present disclosure also relates to methods for treating non-small cell lung cancer (NSCLC) with CRAC inhibitors, and to methods for identifying therapeutics for treating and of diagnosing cancer.

Provided is a method for treating non-small cell lung cancer with wild-type EGFR gene and / or KRAS gene by administering to a subject in need thereof, an effective amount of a triazolone compound according to the following formula:a tautomer, or a pharmaceutically acceptable salt thereof, wherein the variables in the structural formulae are defined herein.

Novel compounds for treatment of cancer and disorders associated with angiogenesis function. Also disclosed are a method of preparing the compounds, pharmaceutical compositions and packaged products containing the compounds, a method of using these molecules to treat cancer (e.g., leukemia, non-small cell lung cancer, colon cancer, CNS cancer, melanoma, ovarian cancer, breast cancer, renal cancer, and prostate cancer) and disorders associated with angiogenesis function (e.g., age-related macular degeneration, macular dystrophy, and diabetes), a method of monitoring the treatment, a method of profiling gene expression, and a method of modulating cell growth, cell cycle, apoptosis, or gene expression.