WO2017200263A1 - Composition de biomarqueur comprenant lrp-1 en tant que principe actif pour le diagnostic du cancer résistant à l'irradiation ou la prédiction du pronostic d'une radiothérapie - Google Patents

Composition de biomarqueur comprenant lrp-1 en tant que principe actif pour le diagnostic du cancer résistant à l'irradiation ou la prédiction du pronostic d'une radiothérapie Download PDF

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WO2017200263A1
WO2017200263A1 PCT/KR2017/005054 KR2017005054W WO2017200263A1 WO 2017200263 A1 WO2017200263 A1 WO 2017200263A1 KR 2017005054 W KR2017005054 W KR 2017005054W WO 2017200263 A1 WO2017200263 A1 WO 2017200263A1
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lrp
cancer
radiation
protein
expression level
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PCT/KR2017/005054
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English (en)
Korean (ko)
Inventor
최은경
정성윤
송시열
이경진
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울산대학교 산학협력단
재단법인 아산사회복지재단
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Priority claimed from KR1020170060005A external-priority patent/KR101952649B1/ko
Application filed by 울산대학교 산학협력단, 재단법인 아산사회복지재단 filed Critical 울산대학교 산학협력단
Priority to EP17799620.4A priority Critical patent/EP3460476B1/fr
Priority to US16/302,092 priority patent/US20190203302A1/en
Publication of WO2017200263A1 publication Critical patent/WO2017200263A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/574—Immunoassay; Biospecific binding assay; Materials therefor for cancer
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids

Definitions

  • the present invention relates to a biomarker composition for diagnosing radiation-resistant cancer comprising low density lipoprotein receptor-related protein 1 (LRP-1) as an active ingredient, and a method for diagnosing radiation-resistant cancer using the same.
  • the present invention relates to a biomarker composition for predicting radiotherapy prognosis of a cancer patient including LRP-1 as an active ingredient and a method for predicting radiotherapy prognosis of a cancer patient using the same.
  • cancer The smallest unit of the human body, the cell, normally divides, grows and dies by intracellular control and maintains cell balance. If a cell is damaged for some reason, it is treated and recovered to act as a normal cell, but if it is not recovered, it dies on its own.
  • cancer is defined as a condition in which abnormal cells, which are not controlled for such proliferation and suppression, proliferate excessively, invade surrounding tissues and organs, and cause mass formation and destruction of normal tissues for various reasons. Cancer is the proliferation of non-suppressive cells, which destroys the structure and function of normal cells and organs, so the diagnosis and treatment are of great importance.
  • the present invention is a biomarker composition for diagnosing radiation resistance cancer comprising LRP-1 as an active ingredient, a composition for diagnosing radiation resistance cancer comprising an agent capable of measuring the expression level of LRP-1 as an active ingredient, and a radiation resistant cancer diagnosis using the same.
  • a method, a pharmaceutical composition for enhancing radiosensitivity to cancer cells comprising an LRP-1 protein expression or an activity inhibitor, and a method for screening a radiosensitizer for cancer cells by measuring the expression level of LRP-1 protein are provided.
  • the present invention also provides a biomarker composition for predicting radiotherapy prognosis of cancer patients comprising LRP-1 as an active ingredient, and a prognosis for cancer patients comprising an agent capable of measuring the expression level of LRP-1 as an active ingredient.
  • the present invention provides a composition for predicting and a method for predicting the prognosis of radiation therapy of cancer patients using the same.
  • the present invention provides a low-density lipoprotein receptor-related protein 1 (LRP-1) or a biomarker composition for diagnosing radiation-resistant cancer comprising a gene encoding the same as an active ingredient. to provide.
  • LRP-1 low-density lipoprotein receptor-related protein 1
  • biomarker composition for diagnosing radiation-resistant cancer comprising a gene encoding the same as an active ingredient.
  • the present invention also provides a composition for diagnosing radiation-resistant cancer comprising a formulation capable of measuring the expression level of LRP-1 as an active ingredient.
  • the present invention provides a method for measuring the expression level of LRP-1 to provide information necessary for the diagnosis of radiation resistant cancer.
  • the present invention also provides a pharmaceutical composition for enhancing radiation sensitivity to cancer cells comprising LRP-1 protein expression or activity inhibitor as an active ingredient.
  • the present invention also provides a method for screening a radiation sensitivity enhancer for cancer cells by measuring the expression level of LRP-1 protein.
  • the present invention also provides a biomarker composition for predicting the prognosis of radiation therapy in cancer patients comprising LRP-1 or a gene encoding the same as an active ingredient.
  • the present invention provides a composition for predicting the prognosis of the radiation therapy of cancer patients comprising a formulation capable of measuring the expression level of LRP-1 as an active ingredient.
  • the present invention provides a method of measuring the expression level of LRP-1 to provide information necessary for predicting the prognosis of radiation therapy in cancer patients.
  • the present invention relates to a biomarker composition for diagnosing radiation-resistant cancer or predicting prognosis for radiation-resistant cancer, comprising LRP-1 as an active ingredient, wherein the binding partner protein actually binds to a specific peptide sequence that specifically targets radiation-resistant colorectal cancer tissue.
  • Phosphorus LRP-1 was elucidated and based on this, the possibility of radiotherapy resistance-related factors for cancer or radiotherapy prognostic predictors of cancer patients was suggested.
  • Figure 2 is a result showing a schematic diagram for the construction of a mouse model transplanted with patient colorectal cancer tissue.
  • 3 shows the results of verifying seven candidate groups showing significant mRNA expression differences among the 14 binding partner protein candidate groups screened.
  • Figure 4 is a result of confirming the difference in expression at the protein level for the two candidate groups selected in the mRNA expression difference with or without irradiation. Only LRP-1 of the two candidate groups confirmed the difference in expression and indicated only the result. Radiation Resistance and Sensitivity Two cases each were checked for protein expression according to irradiation or not.
  • Figure 6 shows the results of the binding of LRP-1 and TPSFSKI peptide using immunoprecipitation method.
  • Lysate 0 Gy / 2 Gy Irradiated Colorectal Cancer Tissue Extract Protein
  • IP (B5 phage) 0 Gy / 2 Gy Irradiated Colorectal Cancer Tissue Extract Protein from Immune Sedimentation with Specific Peptide Phage
  • IP (wt phage) 0 Gy / Immune Sedimentation with Peptide-free Phage from 2 Gy Irradiated Colorectal Cancer Tissue Extracted Proteins
  • IP (w / o Ab) 0 Gy / 2 Gy Irradiated Immune Sedimented Without Antibodies from Colorectal Cancer Tissue Extracted Proteins
  • phage lysate radiation resistant colorectal cancer Peptide phage extract protein targeted at irradiation in tissue
  • Antibody LRP-1 antibody.
  • FIG. 7 shows the results of LRP-1 expression in 4 patients with colorectal cancer tissues (2 cases of radiation resistance and 2 cases of radiation sensitivity). It was confirmed that LRP-1 was overexpressed in the radiation-resistant case, but not in the sensitive case, while confirming that the cancer tissue was identical to that of the cancer tissue extracted from the patient's cancer-grafted mouse model.
  • FIG. 8 is a result of verifying the expression of LRP-1 by receiving cancer tissue from 20 patients with poor treatment prognosis as a patient who performed radiation therapy among colon cancer patients. It was confirmed that LRP-1 was overexpressed in cancer tissue of patients with poor prognosis.
  • the present invention provides a low-marker lipoprotein receptor-related protein 1 (LRP-1) or a biomarker composition for diagnosing radiation-resistant cancer comprising a gene encoding the same as an active ingredient.
  • LRP-1 low-marker lipoprotein receptor-related protein 1
  • biomarker composition for diagnosing radiation-resistant cancer comprising a gene encoding the same as an active ingredient.
  • LRP-1 Low density lipoprotein receptor-related protein 1
  • the biomarker composition may further include a conventionally known radiation resistant biomarker, and conventionally known radiation resistant biomarkers include, but are not limited to, CD133, CD144 and CD24.
  • the LRP-1 may bind to a peptide consisting of the amino acid sequence of SEQ ID NO: 1 (TPSFSKI), and the "TPSFSKI” peptide is a peptide targeting a radiation resistant colorectal cancer, and the applicant of Korea It is disclosed in detail in patent application 10-2015-0106580.
  • diagnosis refers to determining the susceptibility of an object to a particular disease or condition, determining whether an object currently has a particular disease or condition, or as long as a person has a particular disease or condition. Determining the prognosis of the object, or therametrics (eg, monitoring the condition of the object to provide information about treatment efficacy).
  • the present invention provides a composition for diagnosing radiation-resistant cancer comprising a formulation capable of measuring the expression level of LRP-1 as an active ingredient.
  • the agent capable of measuring the expression level of LRP-1 includes a primer or probe specifically binding to the LRP-1 gene, an antibody, peptide, aptamer specifically binding to the LRP-1 protein. Or a compound, but is not limited thereto.
  • the present invention also provides a kit for diagnosing radiation-resistant cancer comprising the composition.
  • primer refers to a nucleic acid sequence having a short free 3-terminal hydroxyl group, which is capable of forming base pairs with complementary templates and acting as a starting point for template strand copying. Refers to the sequence. Primers can initiate DNA synthesis in the presence of four different nucleoside triphosphates and reagents for polymerization (ie, DNA polymerase or reverse transcriptase) at appropriate buffers and temperatures. PCR conditions, sense and antisense primer lengths may be appropriately selected according to techniques known in the art.
  • probe refers to a nucleic acid fragment such as RNA or DNA, which is short to several bases to hundreds of bases capable of specifically binding other than mRNA, and is labeled so that the presence or absence of a specific mRNA is expressed. You can check the amount.
  • the probe may be manufactured in the form of an oligonucleotide probe, a single strand DNA probe, a double strand DNA probe, an RNA probe, or the like. Selection of appropriate probes and hybridization conditions may be appropriately selected according to techniques known in the art.
  • the term “antibody” refers to a specific immunoglobulin directed to an antigenic site as is known in the art.
  • the antibody in the present invention means an antibody that specifically binds to LRP-1 of the present invention, and the antibody can be prepared according to conventional methods in the art. Forms of such antibodies include polyclonal antibodies or monoclonal antibodies, including all immunoglobulin antibodies.
  • the antibody means a complete form having two full length light chains and two full length heavy chains.
  • the said antibody also contains special antibodies, such as a humanized antibody.
  • the kit of the present invention includes an antibody that specifically binds to a marker component, a secondary antibody conjugate conjugated with a label that is developed by reaction with a substrate, a color substrate solution to be color-reacted with the label, a wash solution, It may include an enzyme stopping solution and the like, and may be prepared in a number of separate packaging or compartments containing the reagent components used.
  • the term "peptide” has the advantage of high binding power to the target material, and no degeneration occurs even during thermal / chemical treatment.
  • the small size of the molecule can be used as a fusion protein by attaching to other proteins. Specifically, since it can be used by attaching to a polymer protein chain, it can be used as a diagnostic kit and drug delivery material.
  • aptamer refers to a particular kind of single-stranded nucleic acid (DNA, RNA or modified nucleic acid) that has a stable tertiary structure and which is capable of binding with high affinity and specificity to a target molecule. It means a kind of polynucleotide consisting of). As described above, aptamers are composed of polynucleotides that can bind specifically to antigenic substances like antibodies, but are more stable than proteins, simple in structure, and easy to synthesize. Can be.
  • the present invention comprises the steps of (1) measuring the mRNA expression level or LRP-1 protein expression level of LRP-1 gene from a sample isolated from cancer patients; (2) comparing the mRNA expression level of the LRP-1 gene or the expression level of the LRP-1 protein with a control sample; And (3) determining that the LRP-1 gene mRNA expression level or LRP-1 protein expression level is higher than that of the control sample, wherein the LRP-1 gene is determined to be radiation resistant cancer. do.
  • the method of measuring the mRNA expression level is RT-PCR, competitive RT-PCR (Real-time RT-PCR), RNase protection assay (RPA; RNase protection assay ), Northern blotting and DNA chips are used, but are not limited to these.
  • the method of measuring the protein expression level is Western blot, ELISA (enzyme linked immunosorbent asay), radioimmunoassay (RIA), radioimmunodiffusion, Ouchterlony immunodiffusion method, Rocket immunoelectrophoresis, tissue immunostaining, immunoprecipitation assay, complement fixation assay, FACS and protein chips are used, but are not limited thereto.
  • sample isolated from cancer patients refers to tissues, cells, whole blood, serum, plasma, which differ from the control group in the expression level of the LRP-1 gene or LRP-1 protein, which is a biomarker for radiation-resistant cancer diagnosis.
  • Samples such as saliva, sputum, cerebrospinal fluid, or urine include, but are not limited to.
  • radiation-resistant cancer diagnosis is intended to determine whether cancer cells are radiation-resistant or sensitive for the prediction of radiation treatment strategies and radiation treatment effects of cancer patients.
  • the present invention also provides a pharmaceutical composition for enhancing radiation sensitivity to cancer cells comprising LRP-1 protein expression or activity inhibitor as an active ingredient.
  • the LRP-1 protein expression inhibitor may be an antisense nucleotide, small interfering RNA (siRNA) or short hairpin RNA (shRNA) that complementarily binds to the mRNA of the LRP-1 gene.
  • the LRP-1 protein activity inhibitor may be, but is not limited to, a compound, a peptide, a peptide mimetics, an aptamer, an antibody, or a natural product that specifically binds to the LRP-1 protein.
  • the pharmaceutical composition of the present invention may include chemicals, nucleotides, antisenses, siRNA oligonucleotides, and natural extracts as active ingredients.
  • the pharmaceutical compositions or complex preparations of the present invention may be prepared using pharmaceutically acceptable and physiologically acceptable auxiliaries in addition to the active ingredients, which may include excipients, disintegrants, sweeteners, binders, coatings, swelling agents, lubricants. Solubilizers such as lubricants and flavoring agents can be used.
  • the pharmaceutical composition of the present invention may be preferably formulated into a pharmaceutical composition including one or more pharmaceutically acceptable carriers in addition to the active ingredient for administration.
  • Acceptable pharmaceutical carriers in compositions formulated in liquid solutions are sterile and physiologically compatible, including saline, sterile water, Ringer's solution, buffered saline, albumin injectable solutions, dextrose solution, maltodextrin solution, glycerol, ethanol and One or more of these components may be mixed and used, and other conventional additives such as antioxidants, buffers and bacteriostatic agents may be added as necessary. Diluents, dispersants, surfactants, binders and lubricants may also be added in addition to formulate into injectable formulations, pills, capsules, granules or tablets such as aqueous solutions, suspensions, emulsions and the like.
  • compositions of the present invention may be granules, powders, coated tablets, tablets, capsules, suppositories, syrups, juices, suspensions, emulsions, drops or injectable solutions and sustained release formulations of the active compounds, and the like.
  • the pharmaceutical compositions of the present invention may be administered in a conventional manner via intravenous, intraarterial, intraperitoneal, intramuscular, intraarterial, intraperitoneal, sternum, transdermal, nasal, inhalation, topical, rectal, oral, intraocular or intradermal routes.
  • An effective amount of the active ingredient of the pharmaceutical composition of the present invention means an amount required to prevent or treat a disease.
  • the type of disease the severity of the disease, the type and amount of the active and other ingredients contained in the composition, the type of formulation and the age, body weight, general health, sex and diet of the patient, time of administration, route of administration and composition It can be adjusted according to various factors including the rate of secretion, the duration of treatment, and the drug used concurrently.
  • the composition of the present invention is administered once or several times a day, when the compound is 0.1ng / kg to 10g / kg, a polypeptide,
  • 0.1ng / kg ⁇ 10g / kg antisense nucleotides, siRNA, shRNAi, miRNA can be administered at a dose of 0.01ng / kg ⁇ 10g / kg.
  • the present invention (1) contacting the test substance to cancer cells; (2) measuring the level of expression or activity of LRP-1 protein in cancer cells in contact with the test substance; And (3) provides a method for screening a radiation sensitivity enhancer for cancer cells comprising the step of selecting a test substance with reduced expression or activity of the LRP-1 protein compared to the control sample.
  • test material refers to an unknown candidate used in screening to examine whether it affects the expression level of a gene or affects the expression or activity of a protein. do.
  • the sample includes, but is not limited to, chemicals, nucleotides, antisense-RNAs, small interference RNAs (siRNAs), and natural extracts.
  • the present invention also provides a biomarker composition for predicting the prognosis of radiation therapy in cancer patients comprising LRP-1 or a gene encoding the same as an active ingredient.
  • prognostic prediction refers to the act of predicting the progress and outcome of a disease in advance. More specifically, the prognosis prediction may vary according to the physiological or environmental condition of the patient, and is interpreted to mean all actions for predicting the progress of the disease after treatment in consideration of the condition of the patient. Can be.
  • the prognosis prediction may be interpreted as an act of predicting disease-free survival rate or survival rate of cancer patients by predicting the progress and cure of the disease in advance after radiation treatment of cancer patients. For example, predicting "good prognosis" indicates a high level of disease-free survival or survival after cancer treatment, meaning that cancer patients are more likely to be treated, and predicting "prognosis is poor.” The low disease-free survival rate or survival rate of cancer patients after radiation is indicated, which means that the cancer is more likely to recur or die from cancer.
  • the present invention provides a composition for predicting the prognosis of the radiation therapy of cancer patients comprising a formulation capable of measuring the expression level of LRP-1 as an active ingredient.
  • the agent capable of measuring the expression level of LRP-1 includes a primer or probe specifically binding to the LRP-1 gene, an antibody, peptide, aptamer specifically binding to the LRP-1 protein. Or a compound, but is not limited thereto.
  • the present invention provides a kit for predicting the prognosis of the radiation treatment of cancer patients comprising the composition.
  • the present invention comprises the steps of (1) measuring the mRNA expression level or LRP-1 protein expression level of LRP-1 gene from a sample isolated from cancer patients; (2) comparing the mRNA expression level of the LRP-1 gene or the expression level of the LRP-1 protein with a control sample; And (3) determining that the prognosis of radiation therapy is worse when the mRNA expression level of the LRP-1 gene or the expression level of the LRP-1 protein is higher than that of the control sample.
  • the method of measuring the mRNA expression level is RT-PCR, competitive RT-PCR (Real-time RT-PCR), RNase protection assay (RPA; RNase protection assay ), Northern blotting and DNA chips are used, but are not limited to these.
  • the method of measuring the protein expression level is Western blot, ELISA (enzyme linked immunosorbent asay), radioimmunoassay (RIA), radioimmunodiffusion, Ouchterlony immunodiffusion method, Rocket immunoelectrophoresis, tissue immunostaining, immunoprecipitation assay, complement fixation assay, FACS and protein chips are used, but are not limited thereto.
  • cancer refers to breast cancer, cervical cancer, glioma, brain cancer, melanoma, lung cancer, bladder cancer, prostate cancer, leukemia, kidney cancer, liver cancer, colon cancer, pancreatic cancer, gastric cancer, gallbladder cancer, ovarian cancer, It may be, but is not limited to, lymphoma, osteosarcoma, uterine cancer, oral cancer, bronchial cancer, nasopharyngeal cancer, laryngeal cancer, skin cancer, hematologic cancer, thyroid cancer, parathyroid cancer, or ureter cancer.
  • T7Select ® Human colon tumor cDNA Library specific peptide sequence that purchased the target radiation-resistant colon cancer (Novagen); screened a binding partner protein (TPSFSKI Korea Patent Application No. 10-2015-0106580 call). Specifically, three biopanning processes were repeated to design a binding partner protein candidate group, thereby selecting candidate groups to bind more specifically. After a total of three biopanning procedures, probable candidate information was obtained using sequencing and BLAST. The candidate group information is shown in FIG. 1.
  • Q-PCR quantitative PCR was used to identify significant differences in mRNA expression according to radiation-sensitive, resistant colorectal cancer cases and irradiation. Primers for 14 binding partner protein candidate genes obtained through screening were prepared. In addition, cancer tissue was extracted from the model constructed in Example 2 and cryopreserved, and then mRNA was purified and cDNA was synthesized, respectively. Quantitative PCR (Q-PCR) was performed and seven candidate groups with significant expression differences were selected among the 14 candidate groups depending on the irradiation. As a result of confirming the reproducibility of the candidate group, two candidate groups having the largest significant difference in expression were demonstrated, and the results are shown in FIG. 3.
  • LRP-1 is a binding partner protein of the TPSFSKI peptide. This is shown in FIG. 5.
  • or Example 6 is the cancer tissue extracted from the mouse colon cancer tissue transplantation mouse model.
  • the expression of LRP-1 and differences in case-specific expression were evaluated in the colorectal cancer tissues of the original owner of the cancer tissue.
  • the patient's actual cancer tissue paraffin slice slides were provided by Asan Medical Center's Pathology Department, and histological verification was performed by IHC staining technique.
  • the results related to Example 4 and FIG. 5 were obtained, and it was verified that LRP-1 could be applied to actual clinical practice. The results are shown in FIG.
  • Example 7 the expression of LRP-1 was verified in 20 cases of colorectal cancer tissues of patients with poor radiotherapy prognosis.
  • the verification method was verified by the IHC staining technique in the same manner as in Example 7, and as a result, it was confirmed that LRP-1 overexpressed in cancer tissues of colon cancer patients with poor prognosis.

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Abstract

La présente invention concerne une composition de biomarqueur comprenant LRP-1 en tant que principe actif, pour le diagnostic du cancer résistant à l'irradiation, et un procédé de diagnostic d'un cancer résistant à l'irradiation utilisant ladite composition. La présente invention identifie LRP-1, une protéine partenaire de liaison à laquelle une séquence peptidique spécifique qui cible spécifiquement les tissus du cancer du côlon résistant à l'irradiation se lie en pratique et, sur cette base, suggère la possibilité d'un facteur associé à la résistance à la radiothérapie pour le cancer.
PCT/KR2017/005054 2016-05-17 2017-05-16 Composition de biomarqueur comprenant lrp-1 en tant que principe actif pour le diagnostic du cancer résistant à l'irradiation ou la prédiction du pronostic d'une radiothérapie WO2017200263A1 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
EP17799620.4A EP3460476B1 (fr) 2016-05-17 2017-05-16 Composition de biomarqueur comprenant lrp-1 en tant que principe actif pour le diagnostic du cancer résistant à l'irradiation ou la prédiction du pronostic d'une radiothérapie
US16/302,092 US20190203302A1 (en) 2016-05-17 2017-05-16 Biomarker composition comprising lrp-1 as active ingredient, for diagnosis of radiation-resistant cancer or prediction of radiation therapy prognosis

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KR20160060323 2016-05-17
KR10-2016-0060323 2016-05-17
KR10-2017-0060005 2017-05-15
KR1020170060005A KR101952649B1 (ko) 2016-05-17 2017-05-15 Lrp-1을 유효성분으로 포함하는 방사선 저항성 암 진단용 또는 방사선 치료 예후 예측용 바이오마커 조성물

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WO2011054644A1 (fr) * 2009-10-14 2011-05-12 Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V. Variant d'épissage de la protéine apparentée à la lipoprotéine de faible densité 1 en tant que marqueur du cancer
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KR20150106580A (ko) 2014-03-12 2015-09-22 국방과학연구소 바이오 에어로졸 포집을 위한 축상유입형 습식 사이클론

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WO2011054644A1 (fr) * 2009-10-14 2011-05-12 Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V. Variant d'épissage de la protéine apparentée à la lipoprotéine de faible densité 1 en tant que marqueur du cancer
US20150079078A1 (en) * 2012-04-13 2015-03-19 Erasmus University Medical Center Rotterdam Biomarkers for triple negative breast cancer
KR20150106580A (ko) 2014-03-12 2015-09-22 국방과학연구소 바이오 에어로졸 포집을 위한 축상유입형 습식 사이클론

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