Methods of treating lung cancer
Methods of treating cancers comprising FGFR1 gene amplification are provided. In some embodiments, the methods comprise administering a fibroblast growth factor receptor 1 (FGFR1) extracellular domain (ECD) and/or an FGFR1 ECD fusion molecule. In some embodiments, the methods comprise administering a fibroblast growth factor receptor 1 (FGFR1) extracellular domain (ECD) and/or an FGFR1 ECD fusion molecule in combination with at least one additional therapeutic agent.
1. A method of treating lung cancer having an FGFR1 gene amplification in a subject, wherein the cancer overexpresses fibroblast growth factor 2 (FGF2), and wherein at least a portion of the cells of the lung cancer have a ratio of FGFR1 gene to chromosome 8 centromere of at least 1.5, and wherein the FGFR1 gene amplification is indicative of therapeutic responsiveness by the lung cancer to a fibroblast growth factor receptor 1 (FGFR1) extracellular domain (ECD) or an FGFR1 ECD fusion molecule, comprising:
administering a therapeutically effective amount of an FGFR1 ECD or an FGFR1 ECD fusion molecule to the subject.
2. The method of claim 1 , wherein, prior to administration of the FGFR1 ECD or FGFR1 ECD fusion molecule, at least a portion of the cells of the lung cancer have been determined to have a ratio of FGFR1 gene to chromosome 8 centromere of at least 1.5.
3. The method of claim 1 , wherein at least a portion of the cells of the lung cancer having an FGFR1 gene amplification comprise at least three copies of the FGFR1 gene.
4. The method of claim 2 , wherein FGFR1 gene amplification was determined by a method selected from fluorescence in situ hybridization, array comparative genomic hybridization, DNA microarray, spectral karyotyping, quantitative PCR, southern blotting, or sequencing.
5. The method of claim 1 , wherein the lung cancer further overexpresses at least one marker selected from FGFR1, FGFR3IIIc, DKK3, FGF18, and ETV4.
6. The method of claim 5 , wherein the lung cancer overexpresses FGFR1IIIc, wherein FGFR1IIIc is a species of FGFR1.
7. A method of treating lung cancer that overexpresses FGF2 in a subject, wherein overexpression of FGF2 is indicative of therapeutic responsiveness by the lung cancer to a fibroblast growth factor receptor 1 (FGFR1) extracellular domain (ECD) or an FGFR1 ECD fusion molecule, comprising:
administering a therapeutically effective amount of an FGFR1 ECD or an FGFR1 ECD fusion molecule to the subject.
8. The method of claim 7 , wherein, prior to administration of the FGFR1 ECD or FGFR1 ECD fusion molecule, at least a portion of the cells of the lung cancer have been determined to overexpress FGF2.
9. The method of claim 7 , wherein the lung cancer overexpresses at least one additional marker selected from FGFR3IIIc, DKK3, FGF18, and ETV4.
10. The method of claim 7 , wherein the lung cancer does not have an FGFR1 gene amplification.
11. The method of claim 7 , wherein the overexpression is protein overexpression.
12. The method of claim 7 , wherein the overexpression is mRNA overexpression.
13. The method of claim 1 , wherein the method further comprises administering at least one additional therapeutic agent.
14. The method of claim 13 , wherein at least one additional therapeutic agent is selected from docetaxel, paclitaxel, vincristine, carboplatin, cisplatin, oxaliplatin, doxorubicin, 5-fluorouracil (5-FU), leucovorin, pemetrexed, etoposide, topotecan, sorafenib, a VEGF antagonist, a VEGF trap, an anti-VEGF antibody, and bevacizumab.
15. The method of claim 1 , wherein the method comprises administering an FGFR1 ECD.
16. The method of claim 15 , wherein the FGFR1 ECD comprises an amino acid sequence selected from SEQ ID NOs: 1 to 4.
17. The method of claim 1 , wherein the method comprises administering an FGFR1 ECD fusion molecule.
18. The method of claim 17 , wherein the FGFR1 ECD fusion molecule comprises an FGFR1 ECD and a fusion partner, and wherein the fusion partner is Fc.
19. The method of claim 18 , wherein the FGFR1 ECD fusion molecule comprises a sequence selected from SEQ ID NO: 5 and SEQ ID NO: 6.
20. A method of treating lung cancer in a subject, wherein the cancer has an FGFR1 gene amplification and an FGF2 overexpression, the method comprising:
determining in a lung cancer sample from the subject that at least a portion of the cells of the sample have a ratio of FGFR1 gene to chromosome 8 centromere of at least 1.5, and that at least a portion of the cells of the sample overexpress FGF2 mRNA or FGF2 protein, and
administering a therapeutically effective amount of an FGFR1 ECD or an FGFR1 ECD fusion molecule to the subject for whom at least a portion of the cells of the sample are determined to have FGFR1 gene amplification and FGF2 overexpression.