Method for the diagnosis, prognosis and treatment of lung cancer metastasis
The present invention relates to a method for the diagnosis or the prognosis of metastasis in lung cancer which comprises determining if the c-MAF gene is amplified in a primary tumor sample. Likewise, the invention also relates to a method for the diagnosis or the prognosis of metastasis in lung cancer, as well as to a method for determining the tendency to develop bone metastasis with respect to metastasis in other organs, which comprise determining the c-MAF gene expression level. Finally, the invention relates to the use of a c-MAF inhibitor as therapeutic target for treating the lung cancer.
1. An in vitro method for a customized therapy for a subject with lung cancer with bone metastasis comprising,
(i) quantifying the c-MAF gene expression level, amplification or copy number in a tumor sample of said subject;
(ii) determining that the subject has an increase in the expression level, copy number or amplification of the c-MAF gene in the tumor sample with respect to the expression level, copy number or amplification of the c-MAF gene in the control sample, and then said subject receives a therapy aiming to prevent and/or treat the bone metastasis and/or prevent and/or treat bone degradation, wherein the therapy aiming to prevent and/or treat the bone metastasis is a c-MAF inhibitor and/or wherein the therapy aiming to prevent and/or treat the bone degradation is selected from the group consisting of a bisphosphonate, a RANKL inhibitor, a PTH or a PTHLH inhibitor, strontium ranelate, calcitonin, and a cathepsin K inhibitor.
2. The method according to claim 1 , wherein the bone metastasis is osteolytic bone metastasis.
3. The method according to claim 1 , wherein the expression level, copy number or amplification is quantified by means of quantitative polymerase chain reaction (PCR) or a DNA or RNA array, nucleotide hybridization technique, western blot, in situ hybridization, ELISA, immunohistochemistry or a protein array.
4. The method according to claim 1 , wherein the RANKL inhibitor is selected from the group consisting of: a RANKL specific antibody, a RANKL specific nanobody, and osteoprotegerin.
5. The method according to claim 1 , wherein the RANKL inhibitor is the RANKL specific antibody denosumab, the bisphosphonate is zoledronic acid or clodronate, and the RANKL inhibitor is the RANKL specific nanobody ALX-0141.
6. An in vitro method for a customized therapy for a subject with lung cancer, comprising:
(i) detecting c-MAF amplification in a tumor sample of said subject relative to a reference gene copy number, wherein the amplification of the c-MAF gene is determined by means of determining the amplification of the locus 16q22-q24, wherein an amplification of the c-MAF gene with respect to said reference gene copy number is indicative of the presence of metastasis or an increased risk of developing metastasis, and then said subject receives a therapy aiming to prevent and/or treat the metastasis and/or prevent and/or treat bone degradation, wherein the therapy aiming to prevent and/or treat the metastasis is a c-MAF inhibitor and/or wherein the therapy aiming to prevent and/or treat the bone degradation is selected from the group consisting of a bisphosphonate, a RANKL inhibitor, a PTH or a PTHLH inhibitor, strontium ranelate, calcitonin, and a cathepsin K inhibitor.
7. The method according to claim 6 , wherein the metastasis is bone metastasis.
8. The method according to claim 7 , wherein the bone metastasis is osteolytic bone metastasis.
9. The method according to claim 6 , wherein the amplification is quantified by means of in situ hybridization or PCR.
10. The method according to claim 6 , wherein the RANKL inhibitor is selected from the group consisting of: a RANKL specific antibody, a RANKL specific nanobody, and osteoprotegerin.
11. The method according to claim 6 , wherein the RANKL inhibitor is the RANKL specific antibody denosumab, the bisphosphonate is zoledronic acid, and the RANKL inhibitor is the RANKL specific nanobody ALX-0141.
12. The method of claim 1 , wherein the therapy aiming to prevent and/or treat the bone degradation is a bisphosphonate.
13. The method of claim 6 , wherein the therapy aiming to prevent and/or treat the bone degradation is a bisphosphonate.
14. The method according to claim 12 , wherein the bisphosphonate is zoledronic acid or clodronate.
15. The method according to claim 13 , wherein the bisphosphonate is zoledronic acid or clodronate.