Targets for the treatment of ALT-positive cancers
Patent Information
- Authority / Receiving Office
- JP · JP
- Patent Type
- Applications
- Current Assignee / Owner
- THE FRANCIS CRICK INST LTD
- Filing Date
- 2024-05-23
- Publication Date
- 2026-06-09
Smart Images
Figure 2026518747000028 
Figure 2026518747000029 
Figure 2026518747000030
Abstract
Claims
1. A method for treating or preventing ALT-positive cancer in a subject, wherein the method comprises a farnesyl diphosphate synthase (FDPS), a cleavage and polyadenylation specificity factor (CPSF) subunit selected from the list consisting of i) 3 (CPSF3), ii) 1 (CPSF1), and iii) 6 (CPSF6), isopentenyl diphosphate delta-isomerase 1 (IDI1), and B-TFIID.TATA box-binding protein-related factor 1 (BTAF1), zinc finger protein 207 (ZNF207), lysine acetyltransferase 5 (KAT5), signal recognition particle 54 (SRP54), COP9 signalosome subunit 4 (COPS4), proteasome 20S subunit beta 1 (PSMB1), IK cytokine (IK), nucleoporin 155 (NUP155), ubiquitin A-52 residue ribosomal protein fusion product 1 (UBA52), SDS3 homolog SIN3A corepressor complex Components (SUDS3), complement C1Q binding protein (C1QBP), transketolase (TKT), heat shock protein family D (Hsp60) member 1 (HSPD1), proteasome activator complex subunit 3 (PSME3), ubiquitin-like modifier activator enzyme 5 (UBA5), ubiquitin-like modifier activator enzyme 2 (UBA2), SUMO1 activator enzyme subunit 1 (SAE1), proline-rich mitotic checkpoint regulator (PRCC), DNA methyltransferase 1 (DNMT1), basic transcription Factor IIIC subunit 3 (GTF3C3), tRNA methyltransferase 6 (TRMT6), growth factor receptor binding protein 2 (GRB2), ring box protein 1 (RBX1), proteasome 20S subunit alpha 4 (PSMA4), proteasome 20S subunit alpha 5 (PSMA5), RuvB-like protein 1 (RUVBL1), ring finger protein 113A (RNF113A), premRNA processing factor 8 (PRPF8), enhanced exportin 1 (XPO1), nucleoporin A method comprising administering to a subject an inhibitor of one or more genes selected from the list consisting of GLE1 (GLE1), nuclear RNA transport factor 1 (NXF1), mRNA transport factor (RAE1), 60S ribosomal protein L11 (RPL11), 60S ribosomal protein L10a (RPL10A), ubiquitin-conjugating enzyme E2I (UBE2I / UBC9), RAN-binding protein 2 (RANBP2), polyadenylate-binding protein 2 (PABPN1), aldolase A (ALDOA), and nuclear respiratory factor 1 (NRF1).
2. A method for providing diagnosis or prognosis of ALT-positive cancer in a subject, comprising: farnesyl diphosphate synthase (FDPS), cleavage and polyadenylation specificity factor (CPSF) subunit selected from the list consisting of i) 3 (CPSF3), ii) 1 (CPSF1), and iii) 6 (CPSF6), isopentenyl diphosphate delta-isomerase 1 (IDI1), and B-TFIID for the subject.TATA box-binding protein-related factor 1 (BTAF1), zinc finger protein 207 (ZNF207), lysine acetyltransferase 5 (KAT5), signal recognition particle 54 (SRP54), COP9 signalosome subunit 4 (COPS4), proteasome 20S subunit beta 1 (PSMB1), IK cytokine (IK), nucleoporin 155 (NUP155), ubiquitin A-52 residue ribosomal protein fusion product 1 (UBA52), SDS3 homolog SIN3A corepressor compound Combined component (SUDS3), complement C1Q binding protein (C1QBP), transketolase (TKT), heat shock protein family D (Hsp60) member 1 (HSPD1), proteasome activator complex subunit 3 (PSME3), ubiquitin-like modifier activator enzyme 5 (UBA5), ubiquitin-like modifier activator enzyme 2 (UBA2), SUMO1 activator enzyme subunit 1 (SAE1), proline-rich mitotic checkpoint regulator (PRCC), DNA methyltransferase 1 (DNMT1) , basic transcription factor IIIC subunit 3 (GTF3C3), tRNA methyltransferase 6 (TRMT6), growth factor receptor binding protein 2 (GRB2), ring box protein 1 (RBX1), proteasome 20S subunit alpha 4 (PSMA4), proteasome 20S subunit alpha 5 (PSMA5), RuvB-like protein 1 (RUVBL1), ring finger protein 113A (RNF113A), premRNA processing factor 8 (PRPF8), enhanced exportin 1 (XPO1), A method based on the expression status or activity of one or more genes selected from the list consisting of nucleoporin GLE1 (GLE1), nuclear RNA transport factor 1 (NXF1), mRNA transport factor (RAE1), 60S ribosomal protein L11 (RPL11), 60S ribosomal protein L10a (RPL10A), ubiquitin-conjugating enzyme E2I (UBE2I / UBC9), RAN-binding protein 2 (RANBP2), polyadenylate-binding protein 2 (PABPN1), aldolase A (ALDOA), and nuclear respiratory factor 1 (NRF1).
3. The method according to claim 1 or 2, wherein one or more of the genes are chaperone proteins.
4. The method according to claim 3, wherein one or more genes are selected from a list consisting of heat shock protein family D (Hsp60) member 1 (HSPD1).
5. The method according to claim 1 or 2, wherein one or more of the genes are enzymes.
6. The one or more genes are farnesyl diphosphate synthase (FDPS), cleavage and polyadenylation specificity factor (CPSF) subunits, selected from the list consisting of i) 3 (CPSF3), ii) 1 (CPSF1), and iii) 6 (CPSF6), isopentenyl diphosphate delta-isomerase 1 (IDI1), B-TFIID The method according to claim 5, selected from the list consisting of TATA box-binding protein-related factor 1 (BTAF1), lysine acetyltransferase 5 (KAT5), signal recognition particle 54 (SRP54), transketolase (TKT), ubiquitin-like modifier activator enzyme 2 (UBA2), SUMO1 activator enzyme subunit 1 (SAE1), DNA methyltransferase 1 (DNMT1), tRNA methyltransferase 6 (TRMT6), ubiquitin-like modifier activator enzyme 5 (UBA5), RuvB-like enzyme 1 (RUVBL1), ubiquitin-conjugating enzyme E2I (UBE2I / UBC9), RAN-binding protein 2 (RANBP2), polyadenylate-binding protein 2 (PABPN1), and aldolase A (ALDOA).
7. The method according to claim 1 or 2, wherein one or more of the genes are scaffold proteins.
8. The method according to claim 7, wherein one or more genes are selected from a list consisting of COP9 signalosome subunit 4 (COPS4), proteasome subunit beta-1 (PSMB1), IK cytokine (IK), SDS3 homolog SIN3A corepressor complex component (SUDS3), proteasome activator complex subunit 3 (PSME3), growth factor receptor binding protein 2) (GRB2), ring box protein 1 (RBX1), proteasome 20S subunit alpha 4 (PSMA4), proteasome 20S subunit alpha 5 (PSMA5), ring finger protein 113A (RNF113A), and premRNA processing factor 8 (PRPF8).
9. The method according to claim 1 or 2, wherein one or more of the genes are transcription factors.
10. The method according to claim 9, wherein one or more genes are selected from a list consisting of zinc finger protein 207 (ZNF207), basic transcription factor IIIC subunit 3 (GTF3C3), and nuclear respiratory factor 1 (NRF1).
11. The method according to claim 1 or 2, wherein one or more of the genes are transporter proteins.
12. The method according to claim 11, wherein one or more genes are selected from a list consisting of nucleoporin 155 (NUP155), complement C1Q binding protein (C1QBP), enhanced exportin 1 (XPO1), nucleoporin GLE1 (GLE1), nuclear RNA transport factor 1 (NXF1), and mRNA transport factor (RAE1).
13. The method according to claim 1 or 2, wherein the one or more genes are part of the SUMO activating enzyme complex.
14. The method according to claim 13, wherein one or more genes are selected from a list consisting of ubiquitin-like modifying factor activating enzyme 2 (UBA2), SUMO1 activating enzyme subunit 1 (SAE1), ubiquitin-conjugating enzyme E2I (UBE2I / UBC9), and RAN-binding protein 2 (RANBP2).
15. The method according to claim 1 or 2, wherein one or more of the genes have ubiquitin-like modifier activating enzyme activity (GO: 0008641).
16. The method according to claim 15, wherein one or more genes are selected from a list consisting of ubiquitin-like modifier activating enzyme 2 (UBA2), SUMO1 activating enzyme subunit 1 (SAE1), ubiquitin-like modifier activating enzyme 5 (UBA5), ubiquitin-conjugating enzyme E2I (UBE2I / UBC9), and RAN-binding protein 2 (RANBP2).
17. The method according to claim 1 or 2, wherein one or more of the genes are part of a proteasome complex (GO:0000502).
18. The method according to claim 17, wherein one or more genes are selected from a list consisting of proteasome 20S subunit beta-1 (PSMB1), proteasome activator complex subunit 3 (PSME3), proteasome 20S subunit alpha-4 (PSMA4), and proteasome 20S subunit alpha-5 (PSMA5).
19. The method according to claim 1 or 2, wherein one or more of the genes are involved in regulating mRNA metabolic processes (GO: 1903311).
20. The method according to claim 19, wherein one or more genes are selected from a list consisting of proteasome 20S subunit beta 1 (PSMB1), proteasome activator complex subunit 3 (PSME3), ubiquitin A-52 residue ribosomal protein fusion product 1 (UBA52), complement C1Q binding protein (C1QBP), 60S ribosomal protein L11 (RPL11), and 60S ribosomal protein L10a (RPL10A).
21. The method according to claim 1 or 2, wherein one or more of the genes are involved in mRNA splicing (GO:0000398).
22. The method according to claim 21, wherein one or more genes are selected from a list consisting of cleavage and polyadenylation-specific factor 1 (CPSF1), IK cytokine (IK), proline-rich mitotic checkpoint regulator (PRCC), ring finger protein 113A (RNF113A), premRNA processing factor 8 (PRPF8), cleavage and polyadenylation-specific factor subunit 6 (CPSF6), and polyadenylate-binding protein 2 (PABPN1).
23. The method according to claim 1 or 2, wherein one or more of the genes are involved in tRNA processing (GO:0008033).
24. The method according to claim 23, wherein one or more genes are selected from a list consisting of cleavage and polyadenylation specific factor 1 (CPSF1), tRNA methyltransferase 6 (TRMT6), cleavage and polyadenylation specific factor subunit 6 (CPSF6), and polyadenylate-binding protein 2 (PABPN1).
25. The method according to claim 1 or 2, wherein one or more of the genes are involved in RNA transport from the nucleus (GO:0006405).