WO2021058503A1 - Procédé d'identification de produits géniques impliqués dans une réponse incomplète de populations de cellules sensibles aux médicaments - Google Patents

Procédé d'identification de produits géniques impliqués dans une réponse incomplète de populations de cellules sensibles aux médicaments Download PDF

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Publication number
WO2021058503A1
WO2021058503A1 PCT/EP2020/076465 EP2020076465W WO2021058503A1 WO 2021058503 A1 WO2021058503 A1 WO 2021058503A1 EP 2020076465 W EP2020076465 W EP 2020076465W WO 2021058503 A1 WO2021058503 A1 WO 2021058503A1
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Prior art keywords
cell
cells
cancer
drug
treatment
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PCT/EP2020/076465
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English (en)
Inventor
Jérémie ROUX
Agnès PAQUET
Mickael Meyer
Luis Pereira
Original Assignee
Centre National De La Recherche Scientifique - Cnrs -
Universite Cote D'azur
INSERM (Institut National de la Santé et de la Recherche Médicale)
Institut National De Recherche En Informatique Et En Automatique
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Application filed by Centre National De La Recherche Scientifique - Cnrs -, Universite Cote D'azur, INSERM (Institut National de la Santé et de la Recherche Médicale), Institut National De Recherche En Informatique Et En Automatique filed Critical Centre National De La Recherche Scientifique - Cnrs -
Publication of WO2021058503A1 publication Critical patent/WO2021058503A1/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

Definitions

  • the measure of the activity at early time allows to predict accurately the response phenotype of a cell after a time when the contact of the sensitive cell populations with said cancer drug induced only little transcriptional response that would change its profile and allows to recover both non-responding and responding cells that eventually die when its response phenotype manifests itself.
  • the cells are predicted responding for normalized average nuclear intensity > 75 th percentile of the population, preferably > 80 th , 85 th , 90 th , 95 th percentiles of the population and are predicted non-responding for normalized average nuclear intensity ⁇ 25 th percentile of the population, preferably ⁇ 20 th , 15 th , 10 th , 5 th percentiles of the population.
  • the cells are predicted responding for cytoplasmic-nuclear ratio intensity ⁇ 25 th percentile of the population, preferably ⁇ 20 th , 15 th , 10 th , 5 th percentiles of the population and are predicted non-responding for cytoplasmic-nuclear ratio intensity > 75 th percentile of the population, preferably > 80 th , 85 th , 90 th , 95 th percentiles of the population.
  • said combined preparation comprised a cancer drug agent, preferably death receptor targeted agent as described previously, and an inhibitor of Dynamin-l-like protein, preferably dynasore (CAS No. 1202867-00-2) or Mdivi-1 (CAS No. 338967-87-6).
  • a cancer drug agent preferably death receptor targeted agent as described previously
  • an inhibitor of Dynamin-l-like protein preferably dynasore (CAS No. 1202867-00-2) or Mdivi-1 (CAS No. 338967-87-6).
  • Suitable dosage ranges for a compound that modulates the identified gene by the method described previously may be of the order of several hundred micrograms of the agent with a range from about 0.001 to 10 mg/kg/day, preferably in the range from about 0.01 to 1 mg/kg/day.
  • the final number of cells included was: 1529 for control sample, 1481 for TRAIL 50mn 25ng/ml, 1631 for TRAIL 120mn lOng/ml, 1804 for TRAIL 120mn 25ng/ml and 2115 for TRAIL 120mn 40ng/ml.
  • Cell cycle scores were calculated using Seurat CellCycleScoring function, based on previously published gene sets (Revinski et al, 2018). Each sample was first normalized to 10,000 UMIs, and variable features were selected using the vst method.

Abstract

La présente invention concerne un procédé in vitro d'identification d'un produit génique impliqué dans la destruction fractionnelle de populations de cellules sensibles aux médicaments après le traitement du médicament contre le cancer et une préparation combinée comprenant un médicament contre le cancer et un composé qui module l'expression ou l'activité du produit génique identifié par ledit procédé pour une utilisation dans le traitement contre le cancer pour augmenter ladite puissance de médicament contre le cancer et réduire le développement de la résistance au traitement contre le cancer.
PCT/EP2020/076465 2019-09-24 2020-09-23 Procédé d'identification de produits géniques impliqués dans une réponse incomplète de populations de cellules sensibles aux médicaments WO2021058503A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
EP19306181 2019-09-24
EP19306181.9 2019-09-24

Publications (1)

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WO2021058503A1 true WO2021058503A1 (fr) 2021-04-01

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Cited By (1)

* Cited by examiner, † Cited by third party
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CN116589593A (zh) * 2023-04-23 2023-08-15 河南中医药大学第一附属医院 Fret荧光蛋白探针及其应用

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WO2002009755A2 (fr) * 2000-07-27 2002-02-07 Genentech, Inc. Synergisme de l'agoniste du recepteur de l'apo-2l et du cpt-11
JP2013142070A (ja) * 2012-01-11 2013-07-22 Nihon Univ ミトコンドリア分裂阻害剤を用いたｔｒａｉｌ抵抗性の克服

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN116589593A (zh) * 2023-04-23 2023-08-15 河南中医药大学第一附属医院 Fret荧光蛋白探针及其应用
CN116589593B (zh) * 2023-04-23 2024-03-15 河南中医药大学第一附属医院 Fret荧光蛋白探针及其应用

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