NZ730886B2 - Use of fgfr mutant gene panels in identifying cancer patients that will be responsive to treatment with an fgfr inhibitor - Google Patents
Use of fgfr mutant gene panels in identifying cancer patients that will be responsive to treatment with an fgfr inhibitor Download PDFInfo
- Publication number
- NZ730886B2 NZ730886B2 NZ730886A NZ73088615A NZ730886B2 NZ 730886 B2 NZ730886 B2 NZ 730886B2 NZ 730886 A NZ730886 A NZ 730886A NZ 73088615 A NZ73088615 A NZ 73088615A NZ 730886 B2 NZ730886 B2 NZ 730886B2
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- New Zealand
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- fgfr3
- seq
- tacc3
- mutants
- fgfr
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/498—Pyrazines or piperazines ortho- and peri-condensed with carbocyclic ring systems, e.g. quinoxaline, phenazine
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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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
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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
- C12Q2600/00—Oligonucleotides characterized by their use
- C12Q2600/106—Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism
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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
- C12Q2600/00—Oligonucleotides characterized by their use
- C12Q2600/156—Polymorphic or mutational markers
Abstract
Disclosed herein are methods of identifying a cancer patient that will be responsive to treatment with a fibroblast growth factor receptor (FGFR) inhibitor and methods of treating cancer patients. The methods involve evaluating a biological sample from the patient for the presence of one or more FGFR mutants from a FGFR mutant gene panel. Kits and primers for identifying the presence of one or more FGFR mutant genes in a biological sample are also disclosed herein.
Claims (16)
1. A use of a fibroblast growth factor receptor (FGFR) inhibitor in the manufacture of a medicament for treating bladder cancer in a patient in need thereof, wherein: a biological sample from the patient is evaluated for the presence of one or more FGFR3 mutants, and the patient is to be treated with the FGFR inhibitor if the one or more FGFR3 mutants is present in the sample, wherein the one or more FGFR3 mutants comprise FGFR3:TACC3 v1 (FGFR3 exon 18-TACC3 exon 11 fusion), FGFR3:TACC3 v3 (FGFR3 exon 18-TACC3 exon 10 fusion), FGFR3 R248C, FGFR3 S249C, FGFR3 G370C, or FGFR3 Y373C, or any combination thereof, and wherein the FGFR inhibitor comprises a compound having the structure of Formula (I), a N-oxide thereof, a pharmaceutically acceptable salt thereof, or a solvate thereof.
2. A method of identifying a bladder cancer patient that is responsive to treatment with a fibroblast growth factor receptor (FGFR) inhibitor, comprising evaluating a biological sample from the patient for the presence of one or more FGFR3 mutants, wherein the presence of the one or more FGFR3 mutants indicates that the patient is responsive to treatment with the FGFR inhibitor, and wherein the one or more FGFR3 mutants comprise FGFR3:TACC3 v1 (FGFR3 exon 18-TACC3 exon 11 fusion), FGFR3 :TACC3 v3 (FGFR3 exon 18-TACC3 exon 10 fusion), FGFR3 R248C, FGFR3 S249C, FGFR3 G370C, or FGFR3 Y373C, or any combination thereof, and wherein the FGFR inhibitor comprises a compound having the structure of Formula (I), a N-oxide thereof, a pharmaceutically acceptable salt thereof, or a solvate thereof.
3. The use of claim 1 or the method of claim 2, wherein the FGFR inhibitor is the compound of Formula (I)
4. The use of claim 1 or 3 or method of claim 2 or 3, wherein the one or more FGFR3 mutants comprise FGFR3 R248C, FGFR3 S249C, FGFR3 G370C, or FGFR3 Y373C, or any combination thereof.
5. The use of any one of claims 1, 3 or 4, or method of any one of claims 2-4, wherein the cancer is metastatic bladder cancer.
6. The use of any one of claims 1, 3-5 or the method of any one of claims 2-5, wherein said evaluating comprises amplifying a cDNA with a pair of primers that amplify the one or more FGFR3 mutants; optionally, wherein the cDNA is a pre-amplified cDNA.
7. The use or method of claim 6, wherein the one or more FGFR3 mutants and pair of primers are: FGFR3:TACC3 v1 and primers having the sequences of SEQ ID NO:5 and SEQ ID NO:6; FGFR3:TACC3 v3 and primers having the sequences of SEQ ID NO:7 and SEQ ID NO: 8; FGFR3 R248C and primers having the sequences of SEQ ID NO:23 and SEQ ID NO:24 or SEQ ID NO:31 and SEQ ID NO:32; FGFR3 S249C and primers having the sequences of SEQ ID NO:25 and SEQ ID NO:26 or SEQ ID NO:33 and SEQ ID NO:34; FGFR3 G370C and primers having the sequences of SEQ ID NO:27 and SEQ ID NO:28 or SEQ ID NO:35 and SEQ ID NO:36; FGFR3 Y373C and primers having the sequences of SEQ ID NO:29 and SEQ ID NO:30 or SEQ ID NO:37 and SEQ ID NO:38; or any combination thereof.
8. The use or method of claim 6 or 7, wherein the evaluating comprises isolating RNA from the biological sample and synthesizing the cDNA from the isolated RNA, optionally: wherein the method further comprises pre-amplifying the cDNA prior to the amplifying step; and/or wherein said determining step comprises sequencing the amplified cDNA.
9. The use or method of any one of claims 6-8, wherein the amplifying step comprises performing a real-time PCR; optionally: wherein the real-time PCR is performed with one or more probes comprising SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, and/or SEQ ID NO:55; and/or wherein the real-time PCR is performed with one or more 3’ blocking oligonucleotides comprising SEQ ID NO:39, SEQ ID NO:41, and/or SEQ ID NO:42.
10. The use of any one of claims 1 or 3-9, the method of any one of claims 2-9, wherein the one or more FGFR3 mutants comprise FGFR3:TACC3 v1.
11. The use of any one of claims 1 or 3-9, the method of any one of claims 2-9, wherein the one or more FGFR3 mutants comprise FGFR3:TACC3 v3.
12. The use of any one of claims 1 or 3-9, the method of any one of claims 2-9, wherein the one or more FGFR3 mutants comprise FGFR3 R248C.
13. The use of any one of claims 1 or 3-9, the method of any one of claims 2-9, wherein the one or more FGFR3 mutants comprise FGFR3 S249C.
14. The use of any one of claims 1 or 3-9, the method of any one of claims 2-9, wherein the one or more FGFR3 mutants comprise FGFR3 G370C.
15. The use of any one of claims 1 or 3-9, the method of any one of claims 2-9, wherein the one or more FGFR3 mutants comprise FGFR3 Y373C.
16. A use as claimed in any one of claims 1-15, substantially as described herein and with reference to any example thereof.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201462056159P | 2014-09-26 | 2014-09-26 | |
| PCT/US2015/050996 WO2016048833A2 (en) | 2014-09-26 | 2015-09-18 | Use of fgfr mutant gene panels in identifying cancer patients that will be responsive to treatment with an fgfr inhibitor |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| NZ730886A NZ730886A (en) | 2024-08-30 |
| NZ730886B2 true NZ730886B2 (en) | 2024-12-03 |
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