65 results about "Kras mutation" patented technology

Methods for diagnosing and treating cancer associated with an oncogenic Kras mutation in a subject are provided.

The disclosure provides compositions and methods for detecting and predicting acquired resistance to anti-EGFR treatment in colorectal cancers. Also provided are compositions and methods of preventing, reversing or delaying the acquired resistance. The present disclosure also provides kits for use in the methods described herein.

The present invention relates to mutations in Epidermal Growth Factor Receptor (EGFR) and KRAS and methods of detecting such mutations as well as prognostic methods for identifying tumors that are susceptible to anticancer therapy such as chemotherapy and / or kinase inhibitor treatment. The methods involve determining the presence of a mutated EGFR gene or mutated EGFR protein and / or a mutated KRAS gene or mutated KRAS protein in a tumor sample.

The invention provides an allogeneic antigen-presenting cell targeting KRAS mutation, a construction method and a preparation method of intestinal cancer specific CTL cell, which belong to the technical field of tumor targeting, the method for constructing the allogeneic antigen-presenting cell comprises the following steps: 1) analyzing the affinity of a combination of HLA typing and KRAS mutation sequence of a certain intestinal cancer patient, and selecting a combination of synthetic fusion genes with the highest affinity; 2) ligating the synthetic fusion gene to an expression vector to obtain a recombinant vector; and 3) transferring the recombinant vector to a healthy-derived monocyte, and performing induced culture to obtain the allogeneic antigen-presenting cell targeting KRAS mutation. The allogeneic antigen-presenting cell targeting KRAS mutation solve the problem that the allogeneic DC does not match the HLA typing of the patient, and can stimulate a stronger immune response.The colon cancer-specific CTL cell has the good killing effect on target cells.

The invention relates to arenobufagin derivatives with structures shown as a general formula I or pharmaceutically acceptable salts thereof, a preparation method thereof, a pharmaceutical compositioncontaining the derivatives and application of the derivatives. The arenobufagin derivatives have relatively strong inhibitory activity on tumor cell strains with KRAS mutation, and can be used for preparing medicines for treating malignant tumors with KRAS mutation.

The invention discloses a kit, a primer, a probe and a detection agent for detecting tumor gene variation. The kit, the primer, the probe and the detection agent for detecting the tumor gene variationcan be used for detecting tumor driving gene EGFR mutation, KRAS mutation, BRAF mutation, HER2 mutation, MET mutation, EML4-ALK fusion and ROS1 fusion. The fluorescent probe for detecting tumor genevariation, disclosed by the invention, has the advantages that the fluorescent probe is specifically combined with a mutant type DNA template in the PCR process but not combined with a wild type DNA template, so that a mutant type amplification result generates a fluorescence signal, and a wild type amplification result does not generate the fluorescence signal; a final judging result is that themutant type amplification result has a Ct value and the wild type amplification result has no Ct value. The primer and the probe for detecting tumor gene variation, disclosed by the invention, have the advantages of high specificity, simple kit operation, high detection sensitivity and objective and accurate qualitation of tumor gene variation.

Methods of treating cancer with a compound of formula (I) are disclosed. Also provided are methods of treating a cancer with a KRAS mutation or an ALK+ cancer with a compound of formula (I). Further provided are methods of treating KRAS− mutated or ALK+ NSCLC with a compound of formula (I):

The invention provides a method for rapidly detecting the mutation of KRAS gene, to overcome the disadvantages of low sensitivity and inaccuracy in conventional probe melting curve assay. The method for rapidly detecting the mutation of KRAS gene comprises the following steps: (1) designing and synthesizing molecular beacon probe and template amplification primers; (2) extracting the KRAS genome DNA of a detected sample; (3) preparing a reaction system; (4) performing PCR reaction; performing melting curve analysis after the PCR reaction is finished, and determining if a KRAS mutation occurs in the detected sample through the Tm value of a melting peak. The method combines the molecular beacon probe and extension retardance primers, and uses the DNA polymerase without 5'->3' exonuclease activity to detect KRAS mutation rapidly in vitro, thereby saving consumables simultaneously having the characteristics of high sensitivity and specificity which ensure a more reliable detection result.

The invention discloses a cell autophagy inhibitor taking rubiaceae-type cyclopeptides as effective components. The cell autophagy inhibitor is particularly used for inhibiting KRAS mutation, particularly KRAS dependent tumor cell protective autophagy, and promoting tumor cell apoptosis. The inhibitor is preferably a nano-micelle injection and can be applied to preparation of medicines for treating and preventing KRAS related cancers such as colon cancers, rectal cancers, lung cancers and pancreatic cancers. The cell autophagy inhibitor can effectively inhibit tumor cell protective autophagy, the rubiaceae-type cyclopeptides serving as the effective components are wide in source, the extraction process is mature, dosage forms and pharmacy modes are diversified, and the inhibitor can be applied to treatment and prevention of the KRAS related cancers and has a wide clinical application prospect.

The invention relates to a reagent and a method for detecting KRAS mutation. The invention discloses a primer which is particularly suitable for amplifying and identifying the gene mutations at codon 12, 13 and 61 positions of KRAS, wherein the primer is obtained through reasonable design and preference, good in specificity when being used for PCR (Polymerase Chain Reaction) amplification, high in amplification efficiency, capable of rapidly identifying the mutations of different basic groups of a same codon and capable of rapidly identifying the mutations of different codons of a same gene.

The invention provides two specific T cell receptors targeting G12V or G12C mutation epitopes of a KRAS gene and an anti-tumor application. The two T cell receptors respectively consist of an alpha peptide chain and a beta peptide chain. The invention also provides an antigen binding fragment of the T cell receptors, nucleic acid encoding the antigen binding fragment, a vector containing the nucleic acid, and a host cell containing the vector. The invention further provides a method for preparing a G12V mutation-specific T cell receptor of KRAS or an antigen-binding fragment thereof. The specific T cell receptor and the antigen binding fragment thereof can be used as immune effect activators to stimulate the immune response of the body, thereby generating the action effect of resisting tumors and other diseases.

This invention provides methods and compositions for preventing, treating or ameliorating one or more symptoms of a malignant tumor associated with KRAS mutation in a mammal in need thereof, by identifying a tumor cell in the mammal, the tumor cell comprising at least one of: (i) a mutation of the KRAS gene, and (ii) an aberrant expression level of KRAS protein; and administering to the mammal a therapeutically effective amount of a composition comprising one or more RNAi molecules that are active in reducing expression of GST-π.

The invention discloses a Chinese lung adenocarcinoma cell system CAFQ1 and application thereof. The preservation number of the cell system is CCTCC NO: C201774. The cell system has similar protein expression as that of primary tumor tissue, also has chromosome abnormal karyotype and has tumor properties of in-vitro tumor formation properties. By adopting the cell system, properties of lung adenocarcinoma tumor cells can be maintained after continuous in-vitro subculture, and the cell system is applicable to cell materials for researching and developing immunity treatment, diagnosis and medicines for lung adenocarcinoma. The cell system disclosed by the invention comprises ALK: Kras mutations, the two mutations can result normal pulmonary epithelial cell mutations and tumor formation and can promote tumor cell proliferation, therefore, the cell system can be used as powerful tool cells for studying target medicines with ALK; Kras as targets.

The invention relates to methods of treating lung cancer using glutaminase inhibitors. In particular, results demonstrate that lung cancers characterized by an EGFR or KRAS mutation are treated by glutaminase inhibitors.

The invention provides a preparation method of specific CTL of a target KRAS frequent mutation tumor, and belongs to the technical field of tumor treatment. The preparation method comprises the following steps (1) mixing mutation polypeptide KRAS-12D with mutation polypeptide KRAS-12C, mutation polypeptide KRAS-12V, mutation polypeptide KRAS-12A, mutation polypeptide KRAS-12S, mutation polypeptideKRAS-13D and mutation polypeptide KRAS-61H, so as to obtain KRAS mutation polypeptide mixed liquor; (2) adding DC to the KRAS mutation polypeptide mixed liquor obtained in the step (1), and performing culturing so as to obtain antigen presenting cells; and (3) performing co-culturing on the antigen presenting cells and peripheral blood mononuclearcells so as to obtain the specific CTL of the target KRAS frequent mutation tumor. According to the method disclosed by the invention, 7 KRAS mutation antigens are presented at the same time, so that the prepared CTL can specifically recognize 7 KRASmutation antigens.

The invention provides a preparation method of dendritic cells, which belongs to the technical field of tumor treatment. The preparation method comprises the steps of: 1) ligating a fusion gene of human leukocyte antigen (HLA) and KRAS mutation to pCDH or a mammalian expression vector to obtain a recombinant plasmid; 2) transforming the dendritic cells (DC) derived from peripheral blood by electroporation with the recombinant plasmid to obtain the recombinant cells (i-DC); and 3) inducing maturation of the recombinant cells to obtain the mature dendritic cells. In the prior art, antigen-presenting cells are generally loaded by mutating polypeptides, or mutant antigens are transferred into antigen-presenting cells, but the efficiency of both is low, The method converts the fusion gene of KRAS antigen and HLA into the antigen-presenting cells and overexpresses two genes, increases the binding rate of HLA and KRAS mutant antigen, improves the efficiency of presentation, and more easily obtains CTL with specific killing effect.

This invention provides methods and compositions for preventing, treating or ameliorating one or more symptoms of a malignant tumor associated with KRAS mutation in a mammal in need thereof, by identifying a tumor cell in the mammal, the tumor cell comprising at least one of: (i) a mutation of the KRAS gene, and (ii) an aberrant expression level of KRAS protein; and administering to the mammal a therapeutically effective amount of a composition comprising one or more RNAi molecules that are active in reducing expression of GST-π.

The invention relates to the field of life medicine, and particularly relates to a construction method of a Kras mutation related oral mucosa malignant animal model. The construction method of the mouse oral mucosa malignant animal model comprises the steps that the model is constructed by adopting inducible Kras genetic engineering mice in combination with 4-nitroquinoline 1-oxide (4NQO) chemicalinduction, and on the premise of achieving the cancer formation target, the modeling time is shortened as much as possible. A traditional 4NQO chemical induction oral squamous carcinoma animal modelhas the defect of being long in consumed time (larger than or equal to 20 weeks). According to the method, oral squamous carcinoma is successfully induced by combining Kras mutation with 4NQO, only 12weeks are needed from induction to cancer formation, and compared with a traditional animal model, the time is saved by 2 months for the whole experiment.

This invention provides methods and compositions for preventing, treating or ameliorating one or more symptoms of a malignant tumor associated with KRAS mutation in a mammal in need thereof, by identifying a tumor cell in the mammal, the tumor cell comprising at least one of: (i) a mutation of the KRAS gene, and (ii) an aberrant expression level of KRAS protein; and administering to the mammal a therapeutically effective amount of a composition comprising one or more RNAi molecules that are active in reducing expression of GST-π.

The invention provides a T cell receptor (TCR) capable of being specifically combined with a KRASG12V mutation (KRAS G12V) antigen. Short peptide of the mutation antigen is VVGAVGVGK and can form a compound with HLA A1101, and the TCR is specifically combined with the compound. The invention also provides a nucleic acid molecule encoding the TCR and a vector comprising the nucleic acid molecule. In addition, the invention provides a cell for transducing the TCR.

The invention discloses a gene composition, a kit and a method used for detecting pulmonary adenocarcinoma KRAS mutation, and belongs to the technical field of molecular diagnosis. The gene composition consists of the following 25 genes, including ELN, PODN, LAMC3, COL5A3, CRYAB, SOX18, AKT3, FAM101B, TIE1, SH3PXD2A, EXOC3L2, NOTCH1, NDST1, MMRN2, SH3RF3, ZMIZ1, RNF122, FLT4, F10, TLN1, SOX17, PIP5K1C, TMEM255B, WSCD1 and PCDHB3. In the invention, through the above gene composition, a Score scoring model is constructed for detecting the pulmonary adenocarcinoma KRAS mutation, and therefore, the gene composition has the advantages of high accuracy and good sensitivity and specificity, is convenient in operation, can carry out quantitative analysis and has a wide application prospect.

The invention belongs to the field of molecular biology, and more specifically relates to a primer pair and probe combined product, a composition, and a kit used for detecting KRAS mutation, and applications thereof. The combined product comprises a LNA fluorescence probe and primers used for detecting different KRAS gene 2th exon mutation types; wherein the forward primer sequence of the primer pair comprises at least one locked nucleic acid, and / or, the LNA fluorescence probe sequence comprises at least one locked nucleic acid. The primer pair and the probe composition is rapid and convenient in detection, is high in specificity, sensitivity, reliability, detection efficiency, and accuracy, low in detection cost, short in detection time, and low in false positive rate. The kit can be used for detecting KRAS mutation, is capable of providing guidance for clinical diagnosis and treatment of KRAS mutation cancer, and is promising in application prospect.

Methods for diagnosing and treating cancer associated with an oncogenic Kras mutation in a subject are provided.

The invention relates to methods of treating lung cancer using glutaminase inhibitors. In particular, results demonstrate that lung cancers characterized by an EGFR or KRAS mutation are treated by glutaminase inhibitors.

A new method for KRAS gene mutation detection by means of loop-mediated isothermal amplification through ligation mediation includes steps of: (1) a ligation reaction for preparing a dumbbell-like template: adding ligation probe, ligase and a KRAS mutation sequence to a buffer liquid of a ligase, and placing the liquid in a PCR device for ligation, thus obtaining the dumbbell-like template througha reaction; (2) denaturing the dumbbell-like template with a loop-mediated isothermal amplification system, adding a stain and Bst enzyme, uniformly mixing the components, and performing a reaction in a real-time fluorescence PCR device, so that the primer can recognize the dumbbell-like template and trigger the loop-mediated isothermal amplification, and monitoring a fluorescent signal in real time. In the invention, the fluorescence analysis method for monitoring the KRAS mutation in practical samples is successfully constructed. The method for detecting the genome DNA extracted from the KRAS mutation samples has advantages of high sensitivity, specificity and anti-interference capability.

The invention provides an excrement sample DNA gene mutation kit, and relates to the technical field of kits. The excrement sample DNA gene mutation kit comprises KRAS mutation detection and beta-act i n internal reference, firstly, nucleic acid extraction work needs to be performed, the nucleic acid extraction kit is adopted, excrement in a preservation solution is subjected to nucleic acid extraction and Nanodrop detection of A26 / A280, and a nucleic acid extraction method with Fe3O4 magnetic microspheres as a carrier is adopted. By adopting good primer probe design, adopting a PNA technology for detection and arranging different mutation type probes, actual detection modes are diversified, and the overall actual detection effect is good; and in addition, through scientific experimental steps, experimental modes and experimental conditions, the reaction process can be well mastered, then accurate and reliable experimental results are obtained, and the actual specificity and the accuracy are high.

The invention provides a method for treating NSCLC, especially in cases of KRAS mutation, involving the administration of deforolimus.

The invention relates to the technical field of biology, in particular to application of KRAS (kirsten ratsarcoma viral oncogene) serving as a biomarker in pancreatic cancer and provides application of a substance for detecting G12V mutation in KRAS gene or active fragments thereof to preparation of a kit used for assessment of pancreatic cancer treatment effects and / or judgment of pancreatic cancer prognosis. According to discovery of remarkable correlation between KRAS mutation in pre-operation cfDNA and shortening of overall survival and progression-free survival, a prognosis value of KRAS cfDNA assessment is revealed, and a method of how to provide information for clinical treatment of patients suffering from the pancreatic cancer on the basis of cfDNA biomarker detection assistance is founded, and accordingly individual treatment of the pancreatic cancer can be promoted.

Methods are provided for the detection and treatment of cancers having a KRAS mutation, which KRAS mutation may drive tumorigenesis in the cancer. In some embodiments the KRAS+ cancer is a lung adenocarcinoma.