GB2619478A - Treatment of ovarian cancer minimal residual disease - Google Patents
Treatment of ovarian cancer minimal residual disease Download PDFInfo
- Publication number
- GB2619478A GB2619478A GB2314598.0A GB202314598A GB2619478A GB 2619478 A GB2619478 A GB 2619478A GB 202314598 A GB202314598 A GB 202314598A GB 2619478 A GB2619478 A GB 2619478A
- Authority
- GB
- United Kingdom
- Prior art keywords
- biomarker
- agent
- mrd
- level
- cells
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 208000007660 Residual Neoplasm Diseases 0.000 title claims abstract 36
- 206010033128 Ovarian cancer Diseases 0.000 title claims abstract 25
- 206010061535 Ovarian neoplasm Diseases 0.000 title claims abstract 23
- 239000003795 chemical substances by application Substances 0.000 claims abstract 38
- 238000000034 method Methods 0.000 claims abstract 35
- 230000037356 lipid metabolism Effects 0.000 claims abstract 28
- 230000003834 intracellular effect Effects 0.000 claims abstract 7
- 230000004129 fatty acid metabolism Effects 0.000 claims abstract 4
- 239000000090 biomarker Substances 0.000 claims 52
- 210000004027 cell Anatomy 0.000 claims 33
- 108090000623 proteins and genes Proteins 0.000 claims 20
- 108090000765 processed proteins & peptides Proteins 0.000 claims 17
- 102000004196 processed proteins & peptides Human genes 0.000 claims 16
- 229920001184 polypeptide Polymers 0.000 claims 15
- 235000014113 dietary fatty acids Nutrition 0.000 claims 13
- 229930195729 fatty acid Natural products 0.000 claims 13
- 239000000194 fatty acid Substances 0.000 claims 13
- 150000004665 fatty acids Chemical class 0.000 claims 13
- 102000004169 proteins and genes Human genes 0.000 claims 12
- 239000012634 fragment Substances 0.000 claims 11
- 210000001744 T-lymphocyte Anatomy 0.000 claims 7
- 230000007705 epithelial mesenchymal transition Effects 0.000 claims 6
- 230000002438 mitochondrial effect Effects 0.000 claims 6
- 230000035772 mutation Effects 0.000 claims 6
- 239000003814 drug Substances 0.000 claims 5
- 102000039446 nucleic acids Human genes 0.000 claims 5
- 108020004707 nucleic acids Proteins 0.000 claims 5
- 150000007523 nucleic acids Chemical class 0.000 claims 5
- 102100022089 Acyl-[acyl-carrier-protein] hydrolase Human genes 0.000 claims 4
- 102000002666 Carnitine O-palmitoyltransferase Human genes 0.000 claims 4
- 108010018424 Carnitine O-palmitoyltransferase Proteins 0.000 claims 4
- 108010039731 Fatty Acid Synthases Proteins 0.000 claims 4
- 102100031261 Perilipin-1 Human genes 0.000 claims 4
- 102000012141 Peroxisome proliferator-activated receptor alpha Human genes 0.000 claims 4
- 229940079593 drug Drugs 0.000 claims 4
- 108091008725 peroxisome proliferator-activated receptors alpha Proteins 0.000 claims 4
- 101000998027 Homo sapiens Keratin, type I cytoskeletal 17 Proteins 0.000 claims 3
- 102100033511 Keratin, type I cytoskeletal 17 Human genes 0.000 claims 3
- 206010028980 Neoplasm Diseases 0.000 claims 3
- 108010067162 Perilipin-1 Proteins 0.000 claims 3
- 201000011510 cancer Diseases 0.000 claims 3
- 230000015556 catabolic process Effects 0.000 claims 3
- 230000022131 cell cycle Effects 0.000 claims 3
- 210000000254 ciliated cell Anatomy 0.000 claims 3
- 230000007423 decrease Effects 0.000 claims 3
- 230000003647 oxidation Effects 0.000 claims 3
- 238000007254 oxidation reaction Methods 0.000 claims 3
- 238000004393 prognosis Methods 0.000 claims 3
- 102100021641 Acetyl-CoA carboxylase 2 Human genes 0.000 claims 2
- 108010018763 Biotin carboxylase Proteins 0.000 claims 2
- 102000005870 Coenzyme A Ligases Human genes 0.000 claims 2
- 102100034543 Fatty acid desaturase 3 Human genes 0.000 claims 2
- 101710178017 Fatty acid desaturase 3 Proteins 0.000 claims 2
- 108010087894 Fatty acid desaturases Proteins 0.000 claims 2
- 102000013948 Fatty acid-binding protein 4 Human genes 0.000 claims 2
- 108050003772 Fatty acid-binding protein 4 Proteins 0.000 claims 2
- 102100030421 Fatty acid-binding protein 5 Human genes 0.000 claims 2
- 101710083187 Fatty acid-binding protein 5 Proteins 0.000 claims 2
- 102100026748 Fatty acid-binding protein, intestinal Human genes 0.000 claims 2
- 108050008832 Fatty acid-binding protein, intestinal Proteins 0.000 claims 2
- 101000677545 Homo sapiens Long-chain specific acyl-CoA dehydrogenase, mitochondrial Proteins 0.000 claims 2
- 101000760730 Homo sapiens Medium-chain specific acyl-CoA dehydrogenase, mitochondrial Proteins 0.000 claims 2
- 101000929936 Homo sapiens Short/branched chain specific acyl-CoA dehydrogenase, mitochondrial Proteins 0.000 claims 2
- 102000004882 Lipase Human genes 0.000 claims 2
- 108090001060 Lipase Proteins 0.000 claims 2
- 239000004367 Lipase Substances 0.000 claims 2
- 108010013563 Lipoprotein Lipase Proteins 0.000 claims 2
- 102100022119 Lipoprotein lipase Human genes 0.000 claims 2
- 102100021644 Long-chain specific acyl-CoA dehydrogenase, mitochondrial Human genes 0.000 claims 2
- 108010011449 Long-chain-fatty-acid-CoA ligase Proteins 0.000 claims 2
- 102100024590 Medium-chain specific acyl-CoA dehydrogenase, mitochondrial Human genes 0.000 claims 2
- 108010016731 PPAR gamma Proteins 0.000 claims 2
- 102000001406 Perilipin Human genes 0.000 claims 2
- 108060006002 Perilipin Proteins 0.000 claims 2
- 102000012132 Peroxisome proliferator-activated receptor gamma Human genes 0.000 claims 2
- 102100035766 Short/branched chain specific acyl-CoA dehydrogenase, mitochondrial Human genes 0.000 claims 2
- 102100028897 Stearoyl-CoA desaturase Human genes 0.000 claims 2
- NIJJYAXOARWZEE-UHFFFAOYSA-N Valproic acid Chemical group CCCC(C(O)=O)CCC NIJJYAXOARWZEE-UHFFFAOYSA-N 0.000 claims 2
- 125000003275 alpha amino acid group Chemical group 0.000 claims 2
- 150000001413 amino acids Chemical class 0.000 claims 2
- 238000002619 cancer immunotherapy Methods 0.000 claims 2
- 230000004136 fatty acid synthesis Effects 0.000 claims 2
- 235000019421 lipase Nutrition 0.000 claims 2
- 238000012216 screening Methods 0.000 claims 2
- 210000001519 tissue Anatomy 0.000 claims 2
- DZLOHEOHWICNIL-QGZVFWFLSA-N (2R)-2-[6-(4-chlorophenoxy)hexyl]-2-oxiranecarboxylic acid ethyl ester Chemical compound C=1C=C(Cl)C=CC=1OCCCCCC[C@]1(C(=O)OCC)CO1 DZLOHEOHWICNIL-QGZVFWFLSA-N 0.000 claims 1
- WHYGBVWGARJOCS-UHFFFAOYSA-N 2-benzyl-3-(4-chlorophenyl)-5-(4-nitrophenyl)-1h-pyrazolo[1,5-a]pyrimidin-7-one Chemical compound C1=CC([N+](=O)[O-])=CC=C1C1=CC(=O)N(NC(CC=2C=CC=CC=2)=C2C=3C=CC(Cl)=CC=3)C2=N1 WHYGBVWGARJOCS-UHFFFAOYSA-N 0.000 claims 1
- BBGOSBDSLYHMRA-UHFFFAOYSA-N 4-[1-[4-cyclobutyl-2-methyl-5-(5-methyl-1h-1,2,4-triazol-3-yl)benzoyl]piperidin-4-yl]benzonitrile Chemical compound N1C(C)=NN=C1C1=CC(C(=O)N2CCC(CC2)C=2C=CC(=CC=2)C#N)=C(C)C=C1C1CCC1 BBGOSBDSLYHMRA-UHFFFAOYSA-N 0.000 claims 1
- YFEOVRCUSPPGFZ-UHFFFAOYSA-N 4-[1-[5-[5-(methoxymethyl)-2-(trifluoromethyl)-1H-imidazol-4-yl]-2,4-dimethylbenzoyl]azetidin-3-yl]benzonitrile Chemical compound COCc1[nH]c(nc1-c1cc(C(=O)N2CC(C2)c2ccc(cc2)C#N)c(C)cc1C)C(F)(F)F YFEOVRCUSPPGFZ-UHFFFAOYSA-N 0.000 claims 1
- VCWLZDVWHQVAJU-UHFFFAOYSA-N 4-methylidene-2-octyl-5-oxotetrahydrofuran-3-carboxylic acid Chemical compound CCCCCCCCC1OC(=O)C(=C)C1C(O)=O VCWLZDVWHQVAJU-UHFFFAOYSA-N 0.000 claims 1
- 101150092254 ASF1 gene Proteins 0.000 claims 1
- 102100022279 Aldehyde dehydrogenase family 3 member B2 Human genes 0.000 claims 1
- 102100037437 Beta-defensin 1 Human genes 0.000 claims 1
- 102100024935 CBY1-interacting BAR domain-containing protein 2 Human genes 0.000 claims 1
- 102100035355 Cadherin-related family member 3 Human genes 0.000 claims 1
- 102100036289 Calcium-binding mitochondrial carrier protein SCaMC-2 Human genes 0.000 claims 1
- 102100035768 Calcyphosin-like protein Human genes 0.000 claims 1
- 102100033620 Calponin-1 Human genes 0.000 claims 1
- 102100027943 Carnitine O-palmitoyltransferase 1, liver isoform Human genes 0.000 claims 1
- 102100035366 Centromere protein M Human genes 0.000 claims 1
- 102100037635 Centromere protein U Human genes 0.000 claims 1
- 102100023716 Coiled-coil domain-containing protein 78 Human genes 0.000 claims 1
- 102100038688 Cysteine-rich secretory protein LCCL domain-containing 2 Human genes 0.000 claims 1
- 102100027419 Cytochrome P450 4B1 Human genes 0.000 claims 1
- 102100036218 DNA replication complex GINS protein PSF2 Human genes 0.000 claims 1
- 102100030960 DNA replication licensing factor MCM2 Human genes 0.000 claims 1
- 102100021389 DNA replication licensing factor MCM4 Human genes 0.000 claims 1
- 102100033720 DNA replication licensing factor MCM6 Human genes 0.000 claims 1
- 102100035784 Decorin Human genes 0.000 claims 1
- 102100035890 Delta(24)-sterol reductase Human genes 0.000 claims 1
- 101001046554 Dictyostelium discoideum Thymidine kinase 1 Proteins 0.000 claims 1
- -1 EFCAB 1 Proteins 0.000 claims 1
- 102100031814 EGF-containing fibulin-like extracellular matrix protein 1 Human genes 0.000 claims 1
- 102100037241 Endoglin Human genes 0.000 claims 1
- 229940123469 Fatty acid synthase inhibitor Drugs 0.000 claims 1
- 108090000652 Flap endonucleases Proteins 0.000 claims 1
- 102000004150 Flap endonucleases Human genes 0.000 claims 1
- 102100036242 HLA class II histocompatibility antigen, DQ alpha 2 chain Human genes 0.000 claims 1
- 108010081606 HLA-DQA2 antigen Proteins 0.000 claims 1
- 101000755890 Homo sapiens Aldehyde dehydrogenase family 3 member B2 Proteins 0.000 claims 1
- 101000952040 Homo sapiens Beta-defensin 1 Proteins 0.000 claims 1
- 101000761495 Homo sapiens CBY1-interacting BAR domain-containing protein 2 Proteins 0.000 claims 1
- 101000737802 Homo sapiens Cadherin-related family member 3 Proteins 0.000 claims 1
- 101000715551 Homo sapiens Calcyphosin-like protein Proteins 0.000 claims 1
- 101000945318 Homo sapiens Calponin-1 Proteins 0.000 claims 1
- 101000859570 Homo sapiens Carnitine O-palmitoyltransferase 1, liver isoform Proteins 0.000 claims 1
- 101000737696 Homo sapiens Centromere protein M Proteins 0.000 claims 1
- 101000880512 Homo sapiens Centromere protein U Proteins 0.000 claims 1
- 101000978324 Homo sapiens Coiled-coil domain-containing protein 78 Proteins 0.000 claims 1
- 101000957715 Homo sapiens Cysteine-rich secretory protein LCCL domain-containing 2 Proteins 0.000 claims 1
- 101000736065 Homo sapiens DNA replication complex GINS protein PSF2 Proteins 0.000 claims 1
- 101000583807 Homo sapiens DNA replication licensing factor MCM2 Proteins 0.000 claims 1
- 101000615280 Homo sapiens DNA replication licensing factor MCM4 Proteins 0.000 claims 1
- 101001018484 Homo sapiens DNA replication licensing factor MCM6 Proteins 0.000 claims 1
- 101001018431 Homo sapiens DNA replication licensing factor MCM7 Proteins 0.000 claims 1
- 101001000206 Homo sapiens Decorin Proteins 0.000 claims 1
- 101000929877 Homo sapiens Delta(24)-sterol reductase Proteins 0.000 claims 1
- 101001065272 Homo sapiens EGF-containing fibulin-like extracellular matrix protein 1 Proteins 0.000 claims 1
- 101000881679 Homo sapiens Endoglin Proteins 0.000 claims 1
- 101000994455 Homo sapiens Keratin, type I cytoskeletal 23 Proteins 0.000 claims 1
- 101001023271 Homo sapiens Laminin subunit gamma-2 Proteins 0.000 claims 1
- 101000978212 Homo sapiens Latent-transforming growth factor beta-binding protein 4 Proteins 0.000 claims 1
- 101000783723 Homo sapiens Leucine-rich alpha-2-glycoprotein Proteins 0.000 claims 1
- 101000619602 Homo sapiens Leucine-rich repeat-containing protein 46 Proteins 0.000 claims 1
- 101000685655 Homo sapiens Long-chain fatty acid transport protein 1 Proteins 0.000 claims 1
- 101001051093 Homo sapiens Low-density lipoprotein receptor Proteins 0.000 claims 1
- 101000947699 Homo sapiens Microfibril-associated glycoprotein 4 Proteins 0.000 claims 1
- 101000957259 Homo sapiens Mitotic spindle assembly checkpoint protein MAD2A Proteins 0.000 claims 1
- 101001000104 Homo sapiens Myosin-11 Proteins 0.000 claims 1
- 101000991410 Homo sapiens Nucleolar and spindle-associated protein 1 Proteins 0.000 claims 1
- 101001129132 Homo sapiens Perilipin-1 Proteins 0.000 claims 1
- 101001073422 Homo sapiens Pigment epithelium-derived factor Proteins 0.000 claims 1
- 101000605122 Homo sapiens Prostaglandin G/H synthase 1 Proteins 0.000 claims 1
- 101000657536 Homo sapiens Putative tubulin-like protein alpha-4B Proteins 0.000 claims 1
- 101000864793 Homo sapiens Secreted frizzled-related protein 4 Proteins 0.000 claims 1
- 101000868443 Homo sapiens Sentan Proteins 0.000 claims 1
- 101000691614 Homo sapiens Serine/threonine-protein kinase PLK3 Proteins 0.000 claims 1
- 101000825726 Homo sapiens Structural maintenance of chromosomes protein 4 Proteins 0.000 claims 1
- 101000648544 Homo sapiens Sushi domain-containing protein 2 Proteins 0.000 claims 1
- 101000714202 Homo sapiens Tektin-1 Proteins 0.000 claims 1
- 101000945477 Homo sapiens Thymidine kinase, cytosolic Proteins 0.000 claims 1
- 101000807354 Homo sapiens Ubiquitin-conjugating enzyme E2 C Proteins 0.000 claims 1
- 101000894590 Homo sapiens Uncharacterized protein C20orf85 Proteins 0.000 claims 1
- 101000914180 Homo sapiens Uncharacterized protein C6orf118 Proteins 0.000 claims 1
- 101000743863 Homo sapiens ZW10 interactor Proteins 0.000 claims 1
- 102100032705 Keratin, type I cytoskeletal 23 Human genes 0.000 claims 1
- 102100035159 Laminin subunit gamma-2 Human genes 0.000 claims 1
- 102100023757 Latent-transforming growth factor beta-binding protein 4 Human genes 0.000 claims 1
- 102100035987 Leucine-rich alpha-2-glycoprotein Human genes 0.000 claims 1
- 102100022180 Leucine-rich repeat-containing protein 46 Human genes 0.000 claims 1
- 102100023111 Long-chain fatty acid transport protein 1 Human genes 0.000 claims 1
- 102100024640 Low-density lipoprotein receptor Human genes 0.000 claims 1
- 102100026261 Metalloproteinase inhibitor 3 Human genes 0.000 claims 1
- 102100036103 Microfibril-associated glycoprotein 4 Human genes 0.000 claims 1
- 102100038792 Mitotic spindle assembly checkpoint protein MAD2A Human genes 0.000 claims 1
- 102100036639 Myosin-11 Human genes 0.000 claims 1
- XKLMZUWKNUAPSZ-UHFFFAOYSA-N N-(2,6-dimethylphenyl)-2-{4-[2-hydroxy-3-(2-methoxyphenoxy)propyl]piperazin-1-yl}acetamide Chemical compound COC1=CC=CC=C1OCC(O)CN1CCN(CC(=O)NC=2C(=CC=CC=2C)C)CC1 XKLMZUWKNUAPSZ-UHFFFAOYSA-N 0.000 claims 1
- 102100030991 Nucleolar and spindle-associated protein 1 Human genes 0.000 claims 1
- 101150095279 PIGR gene Proteins 0.000 claims 1
- 102000001487 Perilipin-4 Human genes 0.000 claims 1
- 108010068636 Perilipin-4 Proteins 0.000 claims 1
- 102000001488 Perilipin-5 Human genes 0.000 claims 1
- 108010068642 Perilipin-5 Proteins 0.000 claims 1
- 102100035846 Pigment epithelium-derived factor Human genes 0.000 claims 1
- 102100031574 Platelet glycoprotein 4 Human genes 0.000 claims 1
- 101710202087 Platelet glycoprotein 4 Proteins 0.000 claims 1
- 108010000598 Polycomb Repressive Complex 1 Proteins 0.000 claims 1
- 102000002273 Polycomb Repressive Complex 1 Human genes 0.000 claims 1
- 102100035187 Polymeric immunoglobulin receptor Human genes 0.000 claims 1
- 102100038277 Prostaglandin G/H synthase 1 Human genes 0.000 claims 1
- 102100034805 Putative tubulin-like protein alpha-4B Human genes 0.000 claims 1
- 108091006455 SLC25A25 Proteins 0.000 claims 1
- 101100436059 Schizosaccharomyces pombe (strain 972 / ATCC 24843) cia1 gene Proteins 0.000 claims 1
- 101100407812 Schizosaccharomyces pombe (strain 972 / ATCC 24843) pas4 gene Proteins 0.000 claims 1
- 102100030052 Secreted frizzled-related protein 4 Human genes 0.000 claims 1
- 102100032849 Sentan Human genes 0.000 claims 1
- 102100026209 Serine/threonine-protein kinase PLK3 Human genes 0.000 claims 1
- 102100030684 Sphingosine-1-phosphate phosphatase 1 Human genes 0.000 claims 1
- 101710168942 Sphingosine-1-phosphate phosphatase 1 Proteins 0.000 claims 1
- 102100022842 Structural maintenance of chromosomes protein 4 Human genes 0.000 claims 1
- 102100028854 Sushi domain-containing protein 2 Human genes 0.000 claims 1
- 102100036488 Tektin-1 Human genes 0.000 claims 1
- 102100034838 Thymidine kinase, cytosolic Human genes 0.000 claims 1
- 108010031429 Tissue Inhibitor of Metalloproteinase-3 Proteins 0.000 claims 1
- UHWVSEOVJBQKBE-UHFFFAOYSA-N Trimetazidine Chemical compound COC1=C(OC)C(OC)=CC=C1CN1CCNCC1 UHWVSEOVJBQKBE-UHFFFAOYSA-N 0.000 claims 1
- 102100037256 Ubiquitin-conjugating enzyme E2 C Human genes 0.000 claims 1
- 102100021442 Uncharacterized protein C20orf85 Human genes 0.000 claims 1
- 102100025763 Uncharacterized protein C6orf118 Human genes 0.000 claims 1
- 101100163864 Xenopus laevis asf1aa gene Proteins 0.000 claims 1
- 102100039102 ZW10 interactor Human genes 0.000 claims 1
- DSTWHRGOCUOKDE-UHFFFAOYSA-N [4-(6-fluoro-1,3-benzoxazol-2-yl)phenyl]-[4-(1-hydroxycyclopropanecarbonyl)piperazin-1-yl]methanone Chemical compound FC1=CC2=C(N=C(O2)C2=CC=C(C=C2)C(=O)N2CCN(CC2)C(=O)C2(CC2)O)C=C1 DSTWHRGOCUOKDE-UHFFFAOYSA-N 0.000 claims 1
- 239000000427 antigen Substances 0.000 claims 1
- 230000015572 biosynthetic process Effects 0.000 claims 1
- 108010018719 cytochrome P-450 CYP4B1 Proteins 0.000 claims 1
- 230000000694 effects Effects 0.000 claims 1
- 235000004626 essential fatty acids Nutrition 0.000 claims 1
- 229950006213 etomoxir Drugs 0.000 claims 1
- 239000003112 inhibitor Substances 0.000 claims 1
- 150000002632 lipids Chemical class 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- CYXKNKQEMFBLER-UHFFFAOYSA-N perhexiline Chemical compound C1CCCNC1CC(C1CCCCC1)C1CCCCC1 CYXKNKQEMFBLER-UHFFFAOYSA-N 0.000 claims 1
- 229960000989 perhexiline Drugs 0.000 claims 1
- 229960000213 ranolazine Drugs 0.000 claims 1
- 150000004671 saturated fatty acids Chemical class 0.000 claims 1
- 230000004936 stimulating effect Effects 0.000 claims 1
- 238000003786 synthesis reaction Methods 0.000 claims 1
- 229960001177 trimetazidine Drugs 0.000 claims 1
- 150000004670 unsaturated fatty acids Chemical class 0.000 claims 1
- 235000021122 unsaturated fatty acids Nutrition 0.000 claims 1
- 229960000604 valproic acid Drugs 0.000 claims 1
Classifications
-
- 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
- G01N33/57407—Specifically defined cancers
- G01N33/57449—Specifically defined cancers of ovaries
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2800/00—Detection or diagnosis of diseases
- G01N2800/52—Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2800/00—Detection or diagnosis of diseases
- G01N2800/54—Determining the risk of relapse
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Urology & Nephrology (AREA)
- Hematology (AREA)
- Biomedical Technology (AREA)
- Chemical & Material Sciences (AREA)
- Molecular Biology (AREA)
- Medicinal Chemistry (AREA)
- Physics & Mathematics (AREA)
- Cell Biology (AREA)
- Hospice & Palliative Care (AREA)
- Biotechnology (AREA)
- Food Science & Technology (AREA)
- Oncology (AREA)
- Microbiology (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- General Physics & Mathematics (AREA)
- Pathology (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
The present invention relates to a method of preventing or treating ovarian cancer minimal residual disease (MRD) in a subject. The invention relates to administering an effective amount of an agent which reduces intracellular lipid metabolism, particularly an agent which reduces fatty acid metabolism. The invention also relates to a method of obtaining an indication of the risk to a subject of having or developing a MRD.
Claims (27)
1 . An agent which reduces intracellular lipid metabolism for use in preventing or treating ovarian cancer minimal residual disease (MRD) in a human subject.
2. A method of preventing or treating ovarian cancer minimal residual disease (MRD) in a human subject, the method comprising administering an effective amount of an agent which reduces intracellular lipid metabolism to a subject in need thereof.
3. Use of an agent which reduces intracellular lipid metabolism in the manufacture of a medicament for preventing or treating ovarian cancer minimal residual disease (MRD) in a human subject.
4. A method of obtaining an indication of the risk of a human subject who has previously been treated for ovarian cancer of subsequently having or developing MRD, the method comprising the steps: (a) determining a first level of a lipid metabolism biomarker in a sample of MRD cells obtained from the subject; (b) comparing the first level with a second level of the lipid metabolism biomarker, wherein the second level of lipid metabolism biomarker has been obtained from: (i) a sample of control cells obtained from a control subject or site, or (ii) a reference level; wherein an increase in the first level of lipid metabolism biomarker compared to the second level of lipid metabolism biomarker is indicative of an increased risk of the subject of having or developing MRD.
5. A method of treating ovarian cancer MRD in a human subject, the method comprising the steps of: (a) determining the level of a lipid metabolism biomarker in MRD cells obtained from the subject; (b) comparing the level of lipid biomarker with a reference level; and (c) administering a treatment appropriate for treating ovarian cancer MRD to the subject if the level of lipid metabolism biomarker is above the reference level, thereby treating the ovarian cancer MRD in the human subject.
6. A method of classifying a human subject into an ovarian cancer MRD subgroup, the method comprising the steps: (a) determining the levels of one or more lipid metabolism biomarkers in a sample of MRD cells obtained from the human subject; and (b) classifying the human subject as belonging to an ovarian cancer MRD subgroup based on the levels of the one or more lipid metabolism biomarkers.
7. A method of obtaining an indication of the prognosis of ovarian cancer MRD in a human subject, the method comprising the steps: (a) determining the level of a lipid metabolism biomarker in a sample of MRD cells obtained from the human subject at a first time point and; (b) determining the level of the corresponding lipid metabolism biomarker in a corresponding second sample of MRD cells obtained from the subject at a second (later) time point; wherein an increase in the second level of lipid metabolism biomarker compared to the first level of lipid metabolism biomarker is indicative of a decline in the prognosis of the subject, and wherein a decrease in the second level of lipid metabolism biomarker compared to the first level of lipid metabolism biomarker is indicative of an improvement in the prognosis of the subject.
8. A method of obtaining an indication of the efficacy of a drug which is being used to treat ovarian cancer MRD in a human subject, the method comprising the steps: (a) determining the level a lipid metabolism biomarker in a sample of MRD cells obtained from the human subject at a first time point; and (b) determining the level of the corresponding lipid metabolism biomarker in a corresponding second sample of MRD cells obtained from the subject at a second (later) time point; wherein the drug has been administered to the subject in the interval between the first and second time points, wherein an increase in the second level of lipid metabolism biomarker compared to the first level of lipid metabolism biomarker is indicative of a lack of efficacy of the drug, and wherein a decrease in the second level of lipid metabolism biomarker compared to the first level of lipid metabolism biomarker is indicative of the efficacy of the drug.
9. A method of screening for agents for preventing and/or treating ovarian cancer MRD in a human subject, the method comprising the step: (a) screening for agents which specifically inhibit or reduce the level of intracellular expression of lipid metabolism biomarkers, wherein agents which are identified are ones for preventing and/or treating ovarian cancer MRD.
10. A method as claimed in any one of claims 4 to 9, wherein: (i) the biomarker is a gene, and the level of the biomarker is the expression level of the gene; or (ii) the biomarker is a polypeptide, and the level of the biomarker is the quantity of polypeptide or activity level of the polypeptide.
11. An agent, method or use as claimed in any one of the preceding claims, wherein: (i) the agent is one which reduces fatty acid metabolism, or (ii) the biomarker is one which is involved in fatty acid metabolism.
12. An agent, method or use as claimed in claim 11 , wherein the fatty acid metabolism is: (i) the uptake of fatty acids, (ii) the storage of fatty acids, (iii) the synthesis of fatty acids, or (iv) the catabolism or oxidation of fatty acids.
13. An agent, method or use as claimed in claim 11 or claim 12, wherein the fatty acid is a saturated fatty acid, an unsaturated fatty acid or an essential fatty acid.
14. An agent, method or use as claimed in any one of the preceding claims, wherein: (i) the agent is one which reduces or inhibits the uptake of fatty acids (preferably wherein the agent reduces or inhibits a fatty acid transfer protein); or (ii) the biomarker is one which is involved in the uptake of fatty acids (preferably wherein the biomarker is or encodes a fatty acid transfer protein).
15. An agent, method or use as claimed in claim 14, wherein: (i) the agent is one which reduces or inhibits expression of one or more of: CD36 (cluster of differentiation 36 / fatty acid translocase), FABP2 (fatty acid binding protein 2), FABP4 (fatty acid binding protein 4), FABP5 (fatty acid binding protein 5), LPL (lipoprotein lipase) and PPARA (peroxisome proliferator-activated receptor alpha); or (ii) the biomarker is or encodes one or more of the polypeptides given in (i).
16. An agent as claimed in claim 14, wherein the agent is an FATP inhibitor, preferably Grassofermata.
17. An agent, method or use as claimed in any one of claims 1 -13, wherein: (i) the agent is one which reduces or inhibits the storage of fatty acids (preferably wherein the agent reduces or inhibits a Perilipin); or (ii) the biomarker is one which is involved in fatty acid storage (preferably wherein the biomarker is or encodes a Perilipin).
18. An agent, method or use as claimed in claim 17, wherein: (i) the agent is one which reduces or inhibits expression of one or more of: PLIN1 (lipid droplet-associated protein 1) PLIN4 (lipid droplet-associated protein 4) and PLIN5 (lipid droplet-associated protein 5); or (ii) the biomarker is or encodes one or more of the polypeptides given in (i).
19. An agent, method or use as claimed in any one of claims 1 -13, wherein: (i) the agent is one which reduces or inhibits fatty acid synthesis (preferably wherein the agent reduces or inhibits a fatty acid synthase); or (ii) the biomarker is one which is involved in fatty acid synthesis (preferably wherein the biomarker is or encodes a fatty acid synthase).
20. An agent, method or use as claimed in claim 19, wherein: (i) the agent is one which reduces or inhibits expression of one or more of: FASN (fatty acid synthase), FADS3 (fatty acid desaturase 3), ACACB (Acetyl-CoA carboxylase 2) and SCD (Stearoyl-CoA desaturase); or (ii) the biomarker is or encodes one or more of the polypeptides given in (i).
21. An agent as claimed in claim 19 or claim 20, wherein the agent is a fatty acid synthase inhibitor, preferably C75, TVB-3664, TVB-2640 or FT113.
22. An agent, method or use as claimed in any one of claims 1-13, wherein: (i) the agent is one which reduces or inhibits fatty acid catabolism or oxidation (preferably wherein the agent reduces or inhibits a lipase or carnitine palmitoyltransferase); or (ii) the biomarker one which is involved in fatty acid catabolism or oxidation (preferably wherein the biomarker is or encodes a lipase or carnitine palmitoyltransferase).
23. An agent, method or use as claimed in claim 22, wherein: (i) the agent is one which reduces or inhibits expression of one or more of: ACADL (Acyl-CoA dehydrogenase long chain), ACADM (acyl-CoA dehydrogenase medium chain), ACADSB (acyl-CoA dehydrogenase short/branched chain), ACSL1 (Acyl-CoA synthetase long-chain 1), ACSL6 (Acyl-CoA synthetase long-chain 6), CPT1A or CPT1 (carnitine palmitoyl transferase), PPARA (peroxisome proliferator-activated receptor alpha) and PPARGC1A (peroxisome proliferator-activated receptor gamma); or (ii) the biomarker is or encodes one or more of the polypeptides given in (i).
24. An agent as claimed in claim 22 or claim 23, wherein the agent is selected from the group consisting of Etomoxir, Perhexiline, Trimetazidine and Ranolazine; or is valproic acid.
25. A process for identifying and/or isolating T cells which are capable of recognising ovarian cancer MRD cells in a human subject, the process comprising the steps: (a) identifying a non-synonymous mutation in a polypeptide-encoding gene in the nuclear or mitochondrial genome of the subjectâ s ovarian cancer MRD cells, wherein the mutation is one which is not present in the corresponding gene in the nuclear or mitochondrial genomes of cells of the subjectâ s ovarian cancer and/or non-cancer tissues, wherein the polypeptide is one which is involved in intracellular lipid metabolism, and wherein the polypeptide is a mitochondrial polypeptide; (b) identifying a plurality of fragments of the polypeptide which are encoded by the gene having the non-synonymous mutation, wherein each fragment has an amino acid sequence which spans the site of the mutated amino acid(s), and wherein each fragment is capable of being presented by a mammalian MHC1 molecule; (c) contacting a population of cells from the subject with one or more of the plurality of fragments, wherein the population of cells comprises T cells; and (d) identifying and/or isolating T cells from within the population of cells which recognise one or more of the plurality of fragments, wherein the T cells which are identified and/or isolated in Step (d) are T cells which are capable of recognising ovarian cancer MRD cancer cells in the subject.
26. A method of identifying a peptide neo-antigen for use in cancer immunotherapy in a human subject having ovarian cancer MRD cells, the method comprising the steps: (a) identifying a non-synonymous mutation in a polypeptide-encoding gene in the nuclear or mitochondrial genome of the subjectâ s ovarian cancer MRD cells, wherein the mutation is one which is not present in the corresponding gene in the nuclear or mitochondrial genomes of cells of the subjectâ s ovarian cancer and/or non-cancer tissues, wherein the polypeptide is one which is involved in intracellular lipid metabolism, and wherein the polypeptide is a mitochondrial polypeptide; (b) identifying a plurality of fragments of the polypeptide which are encoded by the gene having the non-synonymous mutation, wherein each fragment has an amino acid sequence which spans the site of the mutated amino acid(s), and wherein each fragment is capable of being presented by a mammalian MHC1 molecule; (c) contacting a population of cells from the subject with one or more of the plurality of fragments, wherein the population of cells comprises T cells; and (d) identifying fragments which are capable of stimulating T cells within the population of cells, wherein fragments which are identified in Step (d) are peptides which are suitable for use in cancer immunotherapy in the subject.
27. A method of determining the status of high-grade serous ovarian carcinoma (HGSOC) MRD cells in a subject, the method comprising: providing a sample of ovarian cancer MRD cells obtained from the subject; and detecting the presence of HGSOC biomarkers in the sample, wherein the method comprises detecting the presence of: (i) a differentiated cell type by detecting one or more of differentiated cell biomarker proteins and/or nucleic acid encoding differentiated cell biomarker proteins selected from the group comprising LTBP4, PTGS1 , SLC25A25, LAMC2, LRG1 , DHCR24, PLK3 and LDLR; (ii) a KRT17 Cluster cell type by detecting one or more of KRT17 Cluster cell biomarker proteins and/or nucleic acid encoding KRT17 Cluster cell biomarker proteins selected from the group comprising SPP1 , IL1 B, IL1 RN, KRT23, ALDH3B2, SUSD2, DEFB1 , HLA-DQA2, CYP4B1 , and PIGR; (iii) an epithelial-mesenchymal transition (EMT) cell type by detecting one or more of epithelial-mesenchymal transition (EMT) biomarker proteins and/or nucleic acid encoding EMT biomarker proteins selected from the group comprising SPARC, SERPINF1 , DCN, SFRP4, CRISPLD2, TIMP3, CNN1 , MYH11 , MFAP4, ENG, EFEMP1 , and RGS 16; (iv) a cell cycle cell type by detecting one or more of cell cycle biomarker proteins and/or nucleic acid encoding cell cycle biomarker proteins selected from the group comprising FEN1 , NUSAP1 , UBE2C, ZWINT, PRC1 , ASF1 B, MCM4, GINS2, CENPM, MCM2, TK1 , MCM6, SMC4, CENPU, and MAD2L1 ; and (v) a ciliated cell type by detecting one or more of ciliated cell biomarker proteins and/or nucleic acid encoding ciliated cell biomarker proteins selected from the group comprising TEKT1 , FAM92B, SNTN, LRRC46, EFCAB 1 , CDHR3, C6orf118, CCDC78, TUBA4B, C20orf85 and CAPSL; wherein the level of the biomarkers is used to determine the fraction of EMT cells in the high-grade serous ovarian carcinoma MRD cells in the subject.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB2102606.7A GB202102606D0 (en) | 2021-02-24 | 2021-02-24 | Treatment of ovarian cancer minimal residual disease |
| PCT/GB2022/050497 WO2022180393A2 (en) | 2021-02-24 | 2022-02-23 | Treatment of ovarian cancer minimal residual disease |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| GB202314598D0 GB202314598D0 (en) | 2023-11-08 |
| GB2619478A true GB2619478A (en) | 2023-12-06 |
Family
ID=75339170
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GBGB2102606.7A Ceased GB202102606D0 (en) | 2021-02-24 | 2021-02-24 | Treatment of ovarian cancer minimal residual disease |
| GB2314598.0A Pending GB2619478A (en) | 2021-02-24 | 2022-02-23 | Treatment of ovarian cancer minimal residual disease |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GBGB2102606.7A Ceased GB202102606D0 (en) | 2021-02-24 | 2021-02-24 | Treatment of ovarian cancer minimal residual disease |
Country Status (2)
| Country | Link |
|---|---|
| GB (2) | GB202102606D0 (en) |
| WO (1) | WO2022180393A2 (en) |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2003024442A2 (en) * | 2001-09-18 | 2003-03-27 | G2M Cancer Drugs Ag | Valproic acid and derivatives for the combinatorial therapeutic treatment of human cancers and for the treatment of tumor metastasis and minimal residual disease |
| US20190142835A1 (en) * | 2017-11-14 | 2019-05-16 | Oregon Health & Science University | Inhibition of autophagy using phospholipase a2 inhibitors |
| WO2020065023A1 (en) * | 2018-09-27 | 2020-04-02 | Vaccibody As | Method for selecting neoepitopes |
| WO2020174211A1 (en) * | 2019-02-27 | 2020-09-03 | Oxford University Innovation Limited | High-grade serous ovarian carcinoma (hgsoc) |
-
2021
- 2021-02-24 GB GBGB2102606.7A patent/GB202102606D0/en not_active Ceased
-
2022
- 2022-02-23 GB GB2314598.0A patent/GB2619478A/en active Pending
- 2022-02-23 WO PCT/GB2022/050497 patent/WO2022180393A2/en active Application Filing
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2003024442A2 (en) * | 2001-09-18 | 2003-03-27 | G2M Cancer Drugs Ag | Valproic acid and derivatives for the combinatorial therapeutic treatment of human cancers and for the treatment of tumor metastasis and minimal residual disease |
| US20190142835A1 (en) * | 2017-11-14 | 2019-05-16 | Oregon Health & Science University | Inhibition of autophagy using phospholipase a2 inhibitors |
| WO2020065023A1 (en) * | 2018-09-27 | 2020-04-02 | Vaccibody As | Method for selecting neoepitopes |
| WO2020174211A1 (en) * | 2019-02-27 | 2020-09-03 | Oxford University Innovation Limited | High-grade serous ovarian carcinoma (hgsoc) |
Non-Patent Citations (1)
| Title |
|---|
| ANDREA GARCIA-GARIJO ET AL, "Determinants for Neoantigen Identification", FRONTIERS IN IMMUNOLOGY, vol. 10, no.1392,(2019-06-24),pages 1 - 19, doi:10.3389/fimmu.2019.01.01392 * abstract * * |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2022180393A3 (en) | 2022-10-13 |
| GB202102606D0 (en) | 2021-04-07 |
| WO2022180393A2 (en) | 2022-09-01 |
| GB202314598D0 (en) | 2023-11-08 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP2434023B1 (en) | Urine markers for detection of bladder cancer | |
| Eschrich et al. | Molecular staging for survival prediction of colorectal cancer patients | |
| US8026055B2 (en) | Materials and methods for prognosing lung cancer survival | |
| EP1668156B9 (en) | Method of diagnosing breast cancer | |
| CA2273847C (en) | Diagnosis of disease state using mrna profiles | |
| US20050095592A1 (en) | Identification of ovarian cancer tumor markers and therapeutic targets | |
| US20030219760A1 (en) | Diagnostic and prognostic tests | |
| KR20150090246A (en) | Molecular diagnostic test for cancer | |
| KR20140044341A (en) | Molecular diagnostic test for cancer | |
| KR20110020853A (en) | Methods of diagnosing rejection of a kidney allograft using genomic or proteomic expression profiling | |
| KR20160117606A (en) | Molecular diagnostic test for predicting response to anti-angiogenic drugs and prognosis of cancer | |
| CN111876478A (en) | Pulmonary nodule diagnostic marker and application | |
| JP2005510251A5 (en) | ||
| GB2619478A (en) | Treatment of ovarian cancer minimal residual disease | |
| EP3294748A1 (en) | Novel methylation site regulating expression of mda-9/syntenin | |
| AU2011236061B2 (en) | Urine markers for detection of bladder cancer | |
| KR102631854B1 (en) | Use of BUB1 as a biomarker for predicting the prognosis of Non-muscle invasive bladder cancer | |
| Ma et al. | Gene Expression Profiles for Recurrence of Lymph Node-positive Primary Breast Cancer in Women Over 40 Years of Age | |
| Kaufmann et al. | Gene expression signatures of breast tissue before and after cross-sex hormone therapy in female-to-male transsexuals | |
| Gelmann | NKX3. 1 Genotype and IGF-1 Interact in Prostate Cancer Risk | |
| NZ618191B2 (en) | Molecular diagnostic test for cancer | |
| NZ584549A (en) | HOXA13 urine marker for detection of bladder cancer |