41 results about "Egfr mutation" patented technology

The invention provides a primer probe set for digital PCR detection of non-small cell lung cancer EGFR mutation and application thereof, and relates to the technical field of digital PCR detection, the primer probe set comprises a primer pair and a probe for specific detection of EGFR gene exon 19 deletion mutation (19del) and exon 21 L858R point mutation, and the 19del mutation probe comprises a plurality of sequences to cover common subtypes. The primer probe group can be combined with a microfluidic digital PCR platform for use, a sample is divided into tens of thousands of microdroplets for amplification, and FAM, HEX, ROX and CY5 fluorescence channel signals are detected to realize absolute quantification. The system provided by the invention has high sensitivity and excellent linearity and precision, is particularly suitable for detecting extremely-low-frequency EGFR mutation in body fluid such as plasma, and has important application value in individualized diagnosis and treatment, curative effect monitoring and drug resistance evaluation of non-small cell lung cancer.

The invention discloses a method for constructing an osimertinib curative effect prediction model based on an elastic score and T790M mutation, and relates to the technical field of biological medicines, and the method is technically characterized in that the osimertinib curative effect prediction model based on the elastic score and the T790M mutation is constructed; the interaction mechanism between the radiomics characteristics and the EGFR mutation state is explored, so that a more accurate decision basis is provided for personalized clinical treatment, and the treatment effect is improved.

The invention relates to a compound for inhibiting EGFR (epidermal growth factor receptor) mutant cancer and a pharmaceutical application thereof. The present disclosure provides a compound of a specific chemical structure, or a pharmaceutically acceptable salt thereof, having an activity of inhibiting and / or degrading a mutant EGFR protein. The present disclosure also provides compositions comprising such compounds, or pharmaceutically acceptable salts thereof. The present disclosure provides a pharmaceutical use of a compound according to the present disclosure, a salt thereof, and a composition comprising the compound according to the present disclosure, a salt thereof, for the treatment or prevention of cancer with EGFR mutation, particularly lung cancer. The disclosure also provides methods for treating or preventing EGFR mutant cancer, particularly lung cancer, comprising administering to a subject in need thereof an effective amount of a compound according to the invention, a salt thereof, or a composition comprising a compound according to the invention, a salt thereof.

The invention discloses treatment of EGFR mutation positive non-small cell lung cancer brain metastasis by administering an effective dose of an EGFR inhibitor. The EGFR inhibitor is N-(2-((2-(dimethylamine) ethyl) (methyl) amine)-4-methoxy-5-((4-(1-deuterated methyl-1H-indol-3-yl) pyrimidine-N '-2-yl) amine) phenyl) acrylamide mesylate.

The invention is applicable to the technical field of disease detection, and particularly relates to an EGFR mutation abundance detection system based on dual-threshold dynamic analysis, the system comprises: a sample processing unit, which is used for separating tissue DNA, is internally provided with a micro-fluidic chip, and is used for quantitatively extracting nucleic acid; the PCR amplification unit is used for amplifying EGFR (epidermal growth factor receptor) sensitive mutation through multiple fluorescent PCR; the signal acquisition unit is used for capturing fluorescence signal intensity through a high-precision photoelectric sensor; the core processing unit is used for executing a dual-threshold abundance grading algorithm through the embedded chip; and the output terminal is used for displaying the abundance level and treatment suggestions through a touch screen. Fluorescence signals are captured through the high-precision photoelectric sensor, the EGFR abundance can be accurately recognized, a basis is provided for achieving an accurate medication scheme for an EGFR sensitive mutation NSCLC patient according to the EGFR abundance, and the detection precision is improved.

This invention provides a DNA origami-based nanoscale ruler and its application. The nanoscale ruler includes a substrate structure, fluorescent indicator chains, and spacing indicator chains. The substrate structure is a three-layer rectangular structure constructed using DNA origami technology to maintain the basic configuration of the nanoscale ruler. Several fluorescent indicator chains are distributed on the first surface of the substrate structure according to a predetermined rule. These fluorescent indicator chains emit fluorescent signals through their fluorescent groups under specific excitation light. Two spacing indicator chains are disposed on the first surface of the substrate structure, forming a predetermined distance between them. These spacing indicator chains are used to target and bind to receptor proteins on the cell membrane via ligand proteins. One technical advantage of this invention is its rational design, which not only enables rapid and accurate determination of the presence of EGFR mutations in tissue samples but also effectively shortens the time required to determine the presence of EGFR mutations.

The application belongs to the field of diagnosis and treatment, and particularly relates to a lung cancer EGFR mutation non-invasive prediction model based on unsupervised decoupling and gate fusion. A multi-modal fusion model is constructed based on enhanced CT images and clinical data of non-small cell lung cancer patients. The application adopts a mask image modeling task, and autonomously learns morphological and texture primitive features of tumors from three-dimensional enhanced CT images without EGFR mutation labels. The application overcomes the dependence on a large amount of labeled data, enables the model to learn visual representations with high discriminability and generalization ability from unlabeled data, and significantly improves feature expression capability. A multi-modal fusion architecture based on a gate mechanism is designed, which can dynamically adjust the contribution weights of deep features, imaging features and clinical information in different samples. Personalized feature fusion for different cases is realized, the limitations of traditional static fusion methods are overcome, and complementary information between multi-source heterogeneous data is fully mined.

The application discloses a heterocyclic EGFR mutation inhibitor in the field of pharmaceutical chemistry, which is a heterocyclic compound shown in general formula I or a stereoisomer or optical isomer thereof or a pharmaceutically acceptable salt thereof, wherein R1, R2, R3, R4, R5, R6, p, X, Y, Z, W, Cy1 and Cy2 are as defined in the claims. The main effect of the heterocyclic EGFR mutation inhibitor is to exert an antitumor effect by inhibiting a mutant EGFR.

The application belongs to the field of biomedicine, and particularly relates to application of fibroblasts in disease treatment; and specifically discloses application of ANXA6 gene in preparation of a diagnostic preparation for treating EGFR mutation-mediated diseases, wherein when overexpression of the ANXA6 gene in CAF cells is detected, the EGFR mutation-mediated diseases cannot be treated by using EGFR targeted drugs; further, the EGFR targeted drugs are epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs).

This invention belongs to the field of tumor biology and drug screening technology, specifically disclosing a human EGFR mutation-driven mouse primary lung cancer cell line, its construction method, and its applications. The cell line, ZST-1, is a human EGFR (L858R / T790M) mutation-driven lung cancer cell line derived from mouse primary lung cancer. It is stable, capable of subcutaneous tumor formation in C57BL / 6 mice, and simultaneously expresses Luciferase and tdTomato reporter genes. Its construction method includes obtaining transgenic mice, virus-induced tumor formation, continuous in vivo passage in nude mice, and in vitro culture and screening steps. This cell line can be applied to in vitro screening and efficacy evaluation of human EGFR mutation-targeting drugs, research on EGFR-TKI resistance mechanisms, tumor bioluminescence imaging and fluorescence tracing, and in vivo tumorigenesis and efficacy experiments in an immune-intact C57BL / 6 background.

The present application provides a method of treating a cancer in a subject in need thereof, where it has been determined that the cancer in the subject comprises one or more atypical epidermal growth factor receptor (EGFR) mutations, comprising administering to the subject (R)-N-(2-(4-(4-cyclopropylpiperazin-1-yl) piperidin-1-yl)-5-((6-(3-(3, 4, 5, 6-tetramethyl-3-piperidin-1-yl)-5-(4-(4-cyclopropylpiperazin-1-yl) piperidin-1-yl)-5-(4-(4-cyclopropylpiperazin-1-yl) piperidin-1-yl)-5-( The present invention relates to a pharmaceutically acceptable salt of 4-(4-(4-(4-(4-(4-(4-(4-(4-(4-(4-(4-(4-(4-(4-(4-(4-(4-(4-(4-(4-(4-(4-(4-(4-(

Disclosed herein are plinabulin and its use for treating a cancer or tumor characterized by expression of a mutant form of an epidermal growth factor receptor (EGFR) protein, comprising administering plinabulin to a subject in need thereof.

The invention relates to an application of osimertinib combined with chidamide in treatment of osimertinib drug-resistant lung cancer, and particularly relates to the following aspects: (1) osimertinib is an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), and shows a remarkable curative effect in treatment of non-small cell lung cancer (NSCLC) patients carrying specific EGFR mutation; (2) chidamide is a novel oral HDACi, can induce cell apoptosis, cell cycle arrest and cell growth inhibition, and shows good tolerance and antitumor activity in various cancer types; and (3) chidamide is taken as an epigenetic regulating agent and can be in synergistic effect with osimertinib, so that the capability of killing lung cancer cells is enhanced. The invention belongs to the technical field of medicines, and particularly provides application of osimertinib combined with chidamide in treatment of osimertinib drug-resistant lung cancer.

This invention relates to a system, kit, and application for the one-pot detection of miRNA and DNA mutations based on CRISPR-Cas12a and aptamers, belonging to the field of biomedical technology. The system for the one-pot detection of miRNA and DNA mutations based on CRISPR-Cas12a and aptamers includes: Cas12a protein, crRNA-R targeting miRNA, aptamer P1, aptamer P2, a linker, AO, and crRNA-D targeting DNA mutations. This invention combines CRISPR / Cas12a with a aptamer-based detection strategy to develop a label-free, direct detection system compatible with smartphones. This system can simultaneously detect EGFR mutations and miRNA-21 expression levels.

This invention discloses a bivalent ligand molecule targeting EGFR and its applications, belonging to the field of drug development technology. Its general structural formula is: [Formula omitted for brevity], where L is a linking group, and M1 and M2 are EGFR protein ligands. This invention forms a bivalent EGFR ligand molecule by covalently linking two EGFR ligands through a linking group. This bivalent ligand molecule can induce additional protein-protein interactions between EGFR monomers, which greatly enhances the binding strength and stability of the drug to EGFR, thereby overcoming the drug resistance problem of traditional EGFR inhibitors and providing a new treatment strategy for cancer patients carrying EGFR mutations and other patients with other diseases.

The present invention relates to a biomarker and an information provision method, for predicting whether or not a mutation is present in an epidermal growth factor receptor (EGFR) by utilizing single-cell multi-omics analysis in a non-small cell lung cancer (NSCLC) patient, and predicting responsiveness to immune checkpoint inhibitor (ICI) therapy. The present invention provides, as an information provision method for predicting responsiveness to ICI therapy in an NSCLC patient, the information provision method comprising the steps of: analyzing a sub-population composition ratio of CD8-positive T cells by performing single-cell multi-omics analysis of a lung sample of a patient; and measuring the frequency of dysfunctional CD8 T cells (CD8_Td) and the frequency of naive-like cells (CD8_Tn) among the CD8-positive T cells, wherein, when the frequency of CD8_Td decreases and the frequency of CD8_Tn increases in EGFR mutation-positive patients, it is predicted that responsiveness to ICI therapy is low.

The present invention relates to treatment of subjects having EGFR exon 20 insertion and other uncommon EGFR mutations.

The invention relates to an EGFR mutation inhibitor and application thereof. Particularly, the invention relates to an EGFR mutation inhibitor with a structure shown in a formula (I), a pharmaceutical composition of the EGFR mutation inhibitor, application of the EGFR mutation inhibitor as the EGFR mutation inhibitor and application of the EGFR mutation inhibitor in preparation of drugs for treating cancers, tumors or metastatic diseases which are at least partially related to EGFR Del19 mutation, EGFR L858R mutation, EGFR L858R / C797S double mutation, EGFR Del19 / C797S double mutation, L858R / T790M / C797S three mutation and Del19 / T790M / C797S three mutation, the invention particularly relates to application in preparation of drugs for treating hyperproliferative diseases and cell death disorder inducing diseases. Wherein the definition of each substituent in the formula (I) is the same as the definition in the specification.

The present application discloses a treatment of EGFR mutation-positive non-small cell lung cancer with brain metastasis by administering an effective dose of an EGFR inhibitor. The EGFR inhibitor is N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxy-5-((4-(1-deuteriomethyl-1H-indol-3-yl)pyrimidin-N'-2-yl)amino)phenyl)acrylamide methanesulfonate.

The present invention relates to treatment of subjects having EGFR exon 20 insertion and other uncommon EGFR mutations.

The application discloses a kind of biotinylated gefitinib probe and its preparation method and application, the probe described in the application is better in stability, sensitivity and accuracy are high, can be long-term preserved, can be used in the experiment needing long time preservation and multiple analysis;It can also be used to detect the binding condition of gefitinib and EGFR in various situations, treat or diagnose cancer;Determine the EGFR mutation type in combination with gene sequencing, the feasibility and effectiveness of the treatment of gefitinib to the EGFR mutation type can also be evaluated, guide drug use.Therefore, biotinylated gefitinib probe is expected to become indispensable tool in precision medicine, so that more patients benefit from gefitinib treatment.

The present invention relates to N4-(indolin-7-yl)-N2-(2-alkoxypyridin-3-yl)pyrimidine-2,4-diamine derivatives, a method for preparing same, and a pharmaceutical composition for the prevention or treatment of cancer comprising same as an active ingredient. The pyrimidine derivatives of the present invention exhibit high inhibitory activity against EGFR mutation and HER2 mutation and thus can be usefully employed in the treatment of cancers involving EGFR or HER2 mutations.

The present disclosure relates to an engineered T-cell Receptors (TCRs) capable of binding to an epitope of an epidermal growth factor receptor (EGFR) comprising a T790M mutation presented on human leukocyte antigen-A (HLA-A)*02:01, wherein the epitope comprises the amino acid sequence of MQLMPFGCLL (SEQ ID NO: 1). Also disclosed are Tcell and BiTE therapies comprising the same, and methods of treating EGFR-TKI resistant lung cancers using the same.

The invention belongs to the technical field of biological medicines, and discloses application of combination of an EGFR (epidermal growth factor receptor) inhibitor and a chemotherapeutic drug in preparation of a drug for treating lung adenocarcinoma containing EGFRp.E746A750del mutation. Tests prove that the EGFR inhibitor osimertinib combined with the chemotherapeutic drug docetaxel shows a synergistic inhibition effect in lung adenocarcinoma PDX and PDO models containing EGFRp.E746A750del mutation, and the combined treatment effect of the osimertinib and the chemotherapeutic drug docetaxel is superior to that of a single drug.

Provided herein are compounds of Formula A having an amide-based backbone linked to a plurality of ring structures, pharmaceutically acceptable salts of these compounds, pharmaceutical compositions thereof, and these compounds for use in medical treatment methods as selective allosteric inhibitors of EGFR mutants for the treatment of cancer, the cancer is such as, for example, lung cancer, colon cancer, breast cancer, endometrial cancer, thyroid cancer, glioma, squamous cell cancer, prostate cancer, non-small cell lung cancer (NSCLC) or a cancer with brain metastasis wherein the cancer is characterized by having at least one EGFR mutation selected from the group consisting of L858R, T790M, and C797S.

The embodiment of the invention provides a bifunctional micro-fluidic chip for guiding cancer medication, a preparation method and a detection method. The chip comprises a substrate, a cell processing layer and a substance injection layer which are sequentially stacked, the substance injection layer is communicated with the cell treatment layer; the cell processing layer comprises a cell mutation detection module and an organoid analysis module, and the substance injection layer comprises a drug injection module; the cell mutation detection module is used for capturing and detecting the type of injected cancer cells; the drug injection module is used for providing a corresponding anti-cancer drug for the organoid analysis module according to the type of injected cancer cells; and the organoid analysis module is used for culturing the injected cancer cells into organoid and monitoring the medication reaction of the organoid in real time. According to the chip, a feasible solution combining cell EGFR mutation detection and organoid-based drug reaction test is realized, and the chip can be used for guiding personalized lung cancer drug treatment.

The present invention provides a novel compound represented by Chemical Formula 1 or a salt thereof and a pharmaceutical composition for treating lung cancer containing same. A pyrimidine derivative compound represented by Chemical Formula 1 effectively inhibits the growth of cancer cells with an ALK mutation and an EGFR mutation, thereby being effectively usable in the treatment of lung cancer.

The invention provides a digital PCR (polymerase chain reaction) method for detecting EGFR (epidermal growth factor receptor) mutation based on a micro-fluidic chip, and relates to the technical field of digital PCR detection.The method comprises the following steps: providing sample DNA (deoxyribonucleic acid); preparing a digital PCR reaction system containing a specific primer probe; adding a sample of the system to a micro-fluidic array chip to generate more than 20,000 micro-reaction units; carrying out PCR (Polymerase Chain Reaction) amplification; fluorescence signals of four channels of FAM, HEX, ROX and CY5 are detected; and interpreting the result according to a specific standard. Key parameters of the platform are determined for the first time, for example, the sample loading amount needs to be smaller than or equal to 105 wild copy / reaction, and a scientific interpretation threshold value is determined. The method is wide in linear range, low in detection limit, good in precision and high in high-frequency mutation consistency compared with NGS, low-frequency mutation which is difficult to find by the NGS can be effectively detected, and a standardized and high-sensitivity detection scheme is provided for NSCLC liquid biopsy.