WO2010073721A1 - Prédiction basée sur un micro-arn de l'efficacité d'une chimiothérapie préopératoire sur le cancer rectal - Google Patents

Prédiction basée sur un micro-arn de l'efficacité d'une chimiothérapie préopératoire sur le cancer rectal Download PDF

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WO2010073721A1
WO2010073721A1 PCT/JP2009/007302 JP2009007302W WO2010073721A1 WO 2010073721 A1 WO2010073721 A1 WO 2010073721A1 JP 2009007302 W JP2009007302 W JP 2009007302W WO 2010073721 A1 WO2010073721 A1 WO 2010073721A1
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mir
predicting
antitumor agent
expression level
therapeutic effect
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PCT/JP2009/007302
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Japanese (ja)
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光生 島田
信浩 栗田
将規 西岡
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国立大学法人徳島大学
大鵬薬品工業株式会社
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Publication of WO2010073721A1 publication Critical patent/WO2010073721A1/fr

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    • 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
    • C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
    • C12Q1/6883—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
    • C12Q1/6886—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • 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
    • C12Q2600/00—Oligonucleotides characterized by their use
    • C12Q2600/106—Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism
    • 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
    • C12Q2600/00—Oligonucleotides characterized by their use
    • C12Q2600/158—Expression markers
    • 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
    • C12Q2600/00—Oligonucleotides characterized by their use
    • C12Q2600/178—Oligonucleotides characterized by their use miRNA, siRNA or ncRNA

Definitions

  • the present invention relates to a method and a diagnostic kit for predicting the therapeutic effect on chemotherapy including a 5-fluorouracil antitumor agent in cancer patients.
  • chemoradiotherapy is performed to reduce the tumor in order to facilitate tumor removal before tumor removal, specifically 5-fluorouracil / leucovorin radiation.
  • 5-Fluorouracil such as therapies and TS-1 (formulation containing tegafur, gimeracil, oteracil potassium 1: 0.4: 1, trade name: TS-1 (registered trademark), manufactured by Taiho Pharmaceutical Co., Ltd.) / irinotecan radiotherapy
  • TS-1 registered trademark
  • neoadjuvant chemoradiation therapy may not be sufficient for tumor reduction depending on the patient's constitution, and it is not necessary if the effect can be predicted before neoadjuvant chemoradiation therapy is performed.
  • Chemoradiotherapy can be reduced, which is preferable from the viewpoint of patient QOL and medical economy.
  • many studies have been conducted on the prediction of the effects of chemoradiotherapy including 5-fluorouracil antitumor agents in colorectal cancer.
  • Met, MMP7 Non-patent Document 1
  • miR miR It has been reported that the expression of -181b and let-7g (Non-patent Document 2) is associated with the therapeutic effect of TS-1.
  • the present invention relates to providing a method capable of accurately predicting the sensitivity of cancer patients who undergo chemotherapy including a 5-fluorouracil antitumor agent.
  • the present invention relates to the following 1) to 6).
  • 1) A method for predicting a therapeutic effect on chemotherapy containing a 5-fluorouracil antitumor agent in a cancer patient comprising the following steps (1) to (2): (1) miR-17, miR-17 *, miR-20a, miR-20a *, miR-20b, miR-92a, miR-106a, miR- contained in a biological sample that may contain cancer cells collected from a patient Measuring the expression level of one or more miRNAs selected from 126 *, miR-142-3p, miR-223, miR-630 and let-7a *; (2) A step of predicting that in any of the following cases (a) to (c), a patient is likely to show a therapeutic effect on chemotherapy including a 5-fluorouracil antitumor agent.
  • An antitumor agent comprising a fluorouracil antitumor agent
  • the prediction method of the present invention is sensitive to chemotherapy (or chemoradiotherapy) administered with a 5-fluorouracil antitumor agent (especially, a combination of tegafur, gimeracil, and oteracil potassium) in cancer patients, particularly colorectal cancer patients. Therefore, when preoperative chemoradiotherapy is performed, etc., it is useful for determining the start and continuation of the chemotherapy, which can contribute to improvement of the patient's QOL and medical economy.
  • a 5-fluorouracil antitumor agent especially, a combination of tegafur, gimeracil, and oteracil potassium
  • miRNA also called microRNA
  • miRNA is a single-stranded RNA of about 20 to 25 bases, which itself does not encode proteins, but regulates its expression by binding to mRNA of other genes. It is thought that it has the function to do.
  • the miRNA of the present invention is selected from 12 types of miRNAs listed in the table below. As in Examples described later, it is possible to predict the therapeutic effect on a 5-fluorouracil antitumor agent using these miRNAs as an index.
  • the base sequences of these miRNAs are all known, and information on each miRNA can be obtained from miRBASE (http://microrana.sanger.ac.uk/) based on the miRBASE Accession No shown in the table below.
  • the miRNA of the present invention includes not only a mature miRNA having a base sequence shown by a sequence number in the following table, but also a pri-miRNA and a pre-miRNA that are precursors thereof.
  • the 5-fluorouracil antitumor agent includes not only 5-fluorouracil but also a 5-fluorouracil derivative whose active metabolite is 5-fluorouracil, specifically, 5-fluorouracil, tegafur. And tegafur / uracil compounding agent, tegafur / gimeracil / oteracil potassium compounding agent, doxyfluridine, capecitabine, carmofur and the like.
  • a tegafur / gimeracil / oteracil potassium compounding agent is preferable, and a tegafur / gimeracil / oteracil potassium compounding agent containing tegafur, gimeracil, and oteracil potassium in a molar ratio of 1: 0.4: 1 is particularly preferable.
  • the chemotherapy in the present invention is not particularly limited as long as it contains a 5-fluorouracil antitumor agent, and another antitumor agent may be used in combination.
  • a 5-fluorouracil antitumor agent for example, you may use together with leucovorin, irinotecan, oxaliplatin, cisplatin, carboplatin, irradiation, etc.
  • the 5-fluorouracil antitumor agent is administered alone or the 5-fluorouracil antitumor agent and radiation are used in combination.
  • the chemotherapy of the present invention may or may not be accompanied by tumor removal before and after its execution, and is preferably a preoperative adjuvant chemotherapy performed before tumor removal.
  • tegafur (generic name, chemical name: 5-fluoro-1- (2-tetrahydrofuryl) -2,4- (1H, 3H) -pyrimidinedione), which is an active ingredient, is a known compound, It is a drug that is activated in vivo to release 5-fluorouracil, which is the main body of antitumor activity.
  • Tegafur can be produced according to a known method, for example, the method described in JP-B-49-10510.
  • gimeracil (generic name, chemical name: 2,4-dihydroxy-5-chloropyridine), which is an active ingredient, is also a known compound and itself has no antitumor activity. It suppresses 5-fluorouracil being metabolized and inactivated in vivo, and can enhance the antitumor effect.
  • an active ingredient oteracil potassium (generic name, chemical name: monopotassium 1,2,3,4-tetrahydro-2,4-dioxo-1,3,5-triazine-6-carboxylate) is also used. It is a known compound and does not itself have antitumor activity, but it is mainly distributed in the gastrointestinal tract and suppresses gastrointestinal disorders by suppressing the activation of 5-fluorouracil at that site. .
  • each active ingredient in the combination of tegafur, gimeracil, and oteracil potassium administered in the chemotherapy of the present invention is not particularly limited as long as each compounding purpose is achieved.
  • gimeracil may be about 0.1 to 5 mol, preferably about 0.2 to 1.5 mol per mol of tegafur. Is about 0.1 to 5 mol, preferably about 0.2 to 2 mol.
  • tegafur: gimeracil: oteracil potassium (molar ratio) 1: 0.4: 1.
  • each active ingredient in the antitumor agent of the present invention are appropriately selected according to the conditions such as the usage, patient age, sex, stage, presence / absence of metastasis, treatment calendar, presence / absence of other antitumor agents, etc.
  • the Each active ingredient is administered once a day or divided into a plurality of times. When each active ingredient is administered in a plurality of times a day, each active ingredient is administered at the same time or at intervals, and the administration sequence is not particularly limited.
  • an oral agent a tablet, a coated tablet, a powder, a granule, a capsule, a liquid agent, etc.
  • an injection a suppository, a patch, and an ointment.
  • An agent etc. can be illustrated.
  • the antitumor agent of the present invention is produced by a generally known formulation method according to each dosage form using a pharmacologically acceptable carrier.
  • pharmacologically acceptable carriers include those commonly used for ordinary drugs, such as excipients, binders, disintegrants, lubricants, diluents, solubilizers, suspending agents, isotonic agents, pH adjustment. Examples include agents, buffers, stabilizers, colorants, flavoring agents, and flavoring agents.
  • colorectal cancer stomach cancer, lung cancer, liver cancer, renal cancer, pancreatic cancer, biliary tract cancer, bladder cancer, cervical cancer, etc.
  • colorectal cancer is preferred. Rectal cancer is particularly preferred.
  • the prediction method of the present invention includes a step (1) of measuring the expression level of the miRNA contained in a biological sample that may contain cancer cells collected from a patient, and the following (a) to (c) In any of the cases, the step (2) is performed in which it is predicted that the patient is likely to have a therapeutic effect on chemotherapy including a 5-fluorouracil antitumor agent.
  • the biological sample is not particularly limited as long as it is a sample collected from a cancer patient and may contain cancer cells.
  • Body fluid blood, urine, etc.
  • tissue, extract thereof, and culture of the collected tissue Etc. can be exemplified.
  • the collection method of a biological sample can be suitably selected according to the kind of biological sample and the cancer type. Preparation of RNA from a biological sample can be usually performed by a known method.
  • the expression level of miRNA can be measured according to a known gene expression level measurement method such as a miRNA microarray method, a Northern blot method, or an RT-PCR method using a probe or primer that specifically hybridizes with each miRNA.
  • a known gene expression level measurement method such as a miRNA microarray method, a Northern blot method, or an RT-PCR method using a probe or primer that specifically hybridizes with each miRNA.
  • Such probes and primers are usually known probes so as to specifically hybridize with a continuous base sequence of at least 15 bases to all bases, preferably 18 bases to all bases in the base sequence of miRNA. Or it designs as a polynucleotide which has said each base length according to a primer design method. The probe need not be completely complementary as long as it specifically hybridizes with each miRNA.
  • a polynucleotide is preferably 70% or more, preferably 80% or more in base sequence, compared to a polynucleotide comprising a base sequence of at least 15 bases continuous in the base sequence of each miRNA or a complementary polynucleotide thereof.
  • the polynucleotide is preferably 90% or more, more preferably 95% or more, particularly preferably 98% or more.
  • identity of the base sequence can be calculated by homology search, sequence alignment program, BLAST, FASTA, ClustalW or the like.
  • “specifically hybridizes” means that a specific hybrid is formed and a nonspecific hybrid is not formed under stringent hybridization conditions.
  • Stringent hybridization conditions can be determined based on the melting temperature (Tm) of a nucleic acid that forms a hybrid in accordance with a generally known method. As washing conditions capable of maintaining a specific hybridized state, the conditions are usually about “1 ⁇ SSC, 0.1% SDS, 37 ° C.”, more strictly “0.5 ⁇ SSC, 0.1% SDS, 42 ° C. ", And more strictly,” 0.1 ⁇ SSC, 0.1% SDS, 65 ° C ".
  • the probe or primer can be prepared by a generally known synthesis method, for example, a commercially available nucleotide synthesizer, based on the base sequence. It can also be prepared by PCR using the base sequence as a template.
  • the probe or primer may be labeled with a commonly used radioactive substance, fluorescent substance, chemiluminescent substance, or enzyme so that miRNA can be easily detected.
  • the measurement of the expression level of miRNA by the miRNA microarray method can be performed by a generally known method.
  • RNA extracted from cancer cells of a patient is dephosphorylated and labeled with a radioisotope or a fluorescent substance. Labeled RNA is hybridized on a miRNA microarray. Subsequently, the amount of the double-stranded probe and RNA formed is measured as a signal derived from the label of the probe.
  • Signal detection can be carried out by measuring with a generally known method such as a radiation detector or a fluorescence detector according to the label of the probe.
  • Measurement of the expression level of miRNA by Northern blotting can be performed by a generally known method. For example, RNA prepared from cancer cells of a patient is transferred to a nylon membrane or the like, and a probe labeled with a radioisotope or a fluorescent substance is hybridized thereto. Subsequently, the amount of the double-stranded probe and RNA formed is measured as a signal derived from the label of the probe. Signal detection can be carried out by measuring with a generally known method such as a radiation detector or a fluorescence detector according to the label of the probe. In addition, it is also possible to carry out according to the protocol of this kit using a commercially available kit for Northern blotting.
  • the measurement of the expression level of miRNA by the RT-PCR method can be performed by a generally known method.
  • a cDNA prepared from RNA prepared from cancer cells of a patient is used as a template, a pair of primers labeled with a radioisotope or a fluorescent substance is hybridized thereto, and PCR is performed according to a generally known method.
  • the amount of the obtained amplified double-stranded DNA is measured as a signal derived from the label of the primer.
  • Signal detection can be carried out by measurement using a generally known method such as a radiation detector or a fluorescence detector. It is also possible to use a commercially available RT-PCR kit according to the protocol of the kit.
  • Step (2) In this step, using the miRNA expression level measured in the above step (1), the possibility of showing a therapeutic effect against chemotherapy including a 5-fluorouracil antitumor agent is predicted.
  • “Showing therapeutic effect” means that the size of the tumor is reduced at a certain rate, specifically, (1) the histological effect is grade 2 or more, and (2) the therapeutic effect by RECIST classification. Satisfying any of the following criteria: (3) that there is a down-stage effect.
  • the “histological effect” is an effect determined by examining a histopathological examination of a patient specimen, and the effect is in accordance with the “Colon Cancer Handling Rules” (6th edition). Is determined by the following criteria.
  • grade-0 ineffective (the cancer cell is hardly affected by treatment such as degeneration and necrosis)
  • grade-1a very mild effect (degeneration / necrosis and melting are observed in less than about 1/3 of cancer)
  • grade-1b mild effect (degeneration / necrosis and lysis of cancer cells are observed in 1/3 or more and less than 2/3 of the cancer)
  • grade-2 considerable effect (remarkable degeneration / necrosis and melting / disappearance in 2/3 or more of cancers)
  • grade-3 Remarkable (when the entire cancer is necrotic or has melted or disappeared. It has been replaced by granulation-like tissue or fibrotic foci).
  • RECIST classification is determined based on the following criteria according to the RECIST (Response Evaluation Criteria in Solid Tumors) guideline Japanese translation JCOG version.
  • PD Progressive disease
  • SD Stable
  • the “down stage effect” is an effect of lowering the stage before and after chemotherapy in stage classification (Stage 0 to IV) based on TNM classification (classification determined by tumor size, presence / absence of metastasis, etc.).
  • TNM classification and the stage classification are determined in accordance with the “Colon Cancer Handling Rules” (6th edition).
  • the prediction of the therapeutic effect is performed by comparing the expression level of miRNA obtained in step (1) with the corresponding cut-off value for predicting the therapeutic effect, and the level thereof. That is, when any one or more of the following conditions (a) to (c) is satisfied, it can be predicted that the patient is highly likely to have a therapeutic effect on chemotherapy including a 5-fluorouracil antitumor agent.
  • any one or more of the above conditions (a) when any one or more of the above conditions (a) is met, it is predicted that the patient is likely to have a histological effect of grade 2 or higher against chemotherapy containing a 5-fluorouracil antitumor agent.
  • any one or more of the above conditions (b) when any one or more of the above conditions (b) is met, it is predicted that the patient is likely to show a therapeutic effect by RECIST classification of PR or higher for chemotherapy including 5-fluorouracil antitumor agent It is also possible to predict that a patient is likely to show a downstage effect for chemotherapy containing a 5-fluorouracil antitumor agent when any one or more of the above conditions (c) is met It is.
  • the cut-off value in the present invention varies depending on various conditions such as the type of miRNA expression level measurement method, it is necessary to set in advance according to the conditions.
  • the cutoff value can be determined by various statistical analysis methods from the expression level of the miRNA of the present invention measured in advance. For example, as a cut-off value for predicting a histological effect of grade 2 or higher, the average value or median value of the expression level of miRNA of the present invention in patients who received chemotherapy containing 5-fluorouracil antitumor agent, etc.
  • ROC analysis to maximize the sum of sensitivity and specificity based on the relationship between the miRNA expression level of the present invention and the histological effect of each patient in patients who received chemotherapy containing 5-fluorouracil antitumor agents
  • required based on can be illustrated.
  • ROC analysis Receiveiver Operating Characteristic
  • the cutoff value for predicting the therapeutic effect and the downstage effect in the RECIST classification of PR or higher can be appropriately set according to the same concept.
  • a cutoff value (ROC analysis) for predicting a histological effect of grade 2 or higher is, for example, miR-142- 3p is 1979.17, miR-223 is 2262.64, and the cut-off value (ROC analysis) when predicting the therapeutic effect over PR in the RECIST classification is miR-17 is 720.69, and miR-17 * is 63.57, miR-20a is 1379.53, miR-20a * is 21.19, miR-20b is 484.55, miR-92a is 801.87, miR-106a is 101.01, miR-223 is 2390 .04, let-7a * is 2.13, predicts downstage effect
  • the case of cut-off values (ROC analysis) miR-126 * is 60.29, miR-223 is 1,349.00, miR-630 is 138.22, exemplified as.
  • the prediction method of the present invention may be applied before (or after) receiving chemotherapy containing a 5-fluorouracil antitumor agent, or may be applied while receiving the chemotherapy.
  • the prediction method of the present invention is useful for determining the start (or resumption) of the chemotherapy, and in the latter case, it is useful for determining the continuation of the chemotherapy.
  • the diagnostic kit of the present invention comprises miR-17, miR-17 *, miR-20a, miR-20a *, miR-20b, miR-92a, miR-106a, miR-126 *, miR-142-3p, miR- Diagnostic reagent for use in the prediction method of the present invention, comprising a primer and / or probe that specifically hybridizes with one or more miRNAs selected from 223, miR-630 and let-7a * Useful as.
  • the diagnostic kit may include one or more components necessary for miRNA detection in addition to the above-described primers and / or probes. Examples of such components include restriction enzymes, polymerases, buffers, dNTPs, labeling and detection reagents, instructions, and the like.
  • Example 1 miRNA microarray analysis Preoperative chemoradiotherapy using TS-1 (manufactured by Taiho Pharmaceutical Co., Ltd.) and radiation was performed on 22 rectal cancer patients. According to the body surface area, TS-1 was taken at a dose of 80 to 120 mg / day in terms of tegafur twice a day for 5 days and then withdrawn for 2 days. Radiation was 2 Gy on the same day as TS-1, that is, for 5 days, and then rested for 2 days. Four courses were implemented with one week as one course (total 40Gy). The initial reference amount (one dose) of TS-1 was taken as the following reference value according to the body surface area, and was orally administered twice a day after breakfast and dinner.
  • TS-1 manufactured by Taiho Pharmaceutical Co., Ltd.
  • miRNA microarray analysis was performed on 821 microRNA using Human miRNA Microarray v2 (manufactured by Agilent Technologies). Signal measurement was performed with Agilent Technologies Microarray Scanner (manufactured by Agilent Technologies), and standardization was performed by replacing with 0.01 when the obtained signal value was 0.01 or less.
  • PR based on RECIST classification 14 cases, SD: 8 cases (response rate 63%).
  • miR-223 was significantly increased, and miR-17, 17 *, 20a, 20a *, 20b, 92a, 106a, and let-7a * were significantly decreased.
  • the cut-off values of the amounts of each miRNA obtained by ROC analysis for predicting a group of PR or higher are 720.69 for miR-17, 63.57 for miR-17 *, and 1379 for miR-20a, respectively.
  • miR-20a * is 21.19, miR-20b is 484.55, miR-92a is 801.87, miR-106a is 101.01, miR-223 is 2390.04, and let-7a * is 2
  • the prediction rate of the group with PR or higher by this cut-off value is 91.7% for miR-17, 91.7% for miR-17 *, 91.7% for miR-20a, and miR- 20a * is 91.7%, miR-20b is 91.7%, miR-92a is 92.3%, miR-106a is 92.3%, miR-223 is 90.0%, let-7 * It was significantly high and 100.0%.
  • miR-17, 17 *, 20a, 20a *, 20b, 92a, 106a, 223, let-7a * are each independently preoperative chemistry containing a 5-fluorouracil antitumor agent, particularly TS-1. Useful as a predictor of RECIST classification in radiation therapy.
  • miR-126 *, 223, and 630 were significantly highly expressed.
  • the cut-off values of each miRNA amount determined by ROC analysis for predicting a group having a downstage effect are miR-126 * of 60.29, miR-223 of 1349.00, and miR-630 of The prediction rate of the group with downstage effect by this cut-off value is 80.0% for miR-126 *, 80.0% for miR-223, and 88.9% for miR-630, respectively.
  • miR-126 *, 223, and 630 are each independently useful as a factor for predicting a downstage effect in preoperative chemoradiotherapy including 5-fluorouracil antitumor agents, particularly TS-1.

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Abstract

Cette invention concerne une méthode qui permet de prédire avec une précision élevée l'efficacité thérapeutique d'une chimiothérapie comprenant un agent antitumoral du type 5-fluorouracil chez un patient atteint du cancer. La méthode selon l'invention qui permet de prédire l'efficacité thérapeutique d'une chimiothérapie comprenant un agent antitumoral du type 5-fluorouracil chez un patient atteint du cancer utilise, à titre de mesure, le niveau d'expression d'un mi-ARN choisi parmi miR-17, miR-17*, miR-20a, miR-20a*, miR-20b, miR-92a, miR-106a, miR-126*, miR-142-3p, miR-223, miR-630 et let-7a* contenu dans un échantillon biologique prélevé sur le patient.
PCT/JP2009/007302 2008-12-26 2009-12-25 Prédiction basée sur un micro-arn de l'efficacité d'une chimiothérapie préopératoire sur le cancer rectal WO2010073721A1 (fr)

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JP2012016294A (ja) * 2010-07-06 2012-01-26 Toray Ind Inc 胃がんの補助化学療法感受性判定用組成物又はキット
JP5548693B2 (ja) * 2009-10-30 2014-07-16 学校法人慶應義塾 抗がん剤の感受性判定方法
WO2014111561A1 (fr) * 2013-01-21 2014-07-24 Deutsches Krebsforschungszentrum Arnmi-142-3p sérique utilisé comme marqueur de pronostic du cancer

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