Method for the diagnosis, prognosis and treatment of prostate cancer metastasis

1. A method for typing a sample of a subject suffering from prostate cancer, and treating said subject to inhibit metastasis or recurrence and/or to avoid, inhibit, and/or treat bone degradation, comprising:

(i) quantifying the expression level, copy number, or amplification of the c-MAF gene in a prostate tumor sample;

(ii) typing said prostate tumor sample by comparing the quantified expression level, copy number, or amplification of c-MAF to a predetermined reference level of c-MAF expression;

(iii) determining that said typing indicates a risk of bone metastasis in said subject; and

(iv) administering a therapeutically effective amount of a therapy aiming to inhibit and/or treat bone metastasis selected from the group consisting of a c-MAF inhibitor, an mTor inhibitor, a Src kinase inhibitor, a COX-2 inhibitor, a CCR5 antagonist and/or Radium-223, and/or an agent capable of avoiding, inhibiting, and/or treating bone degradation to said subject.

2. The method of claim 1 , wherein the agent capable of avoiding, inhibiting, and/or treating bone degradation is selected from the group consisting of a bisphosphonate, a RANKL inhibitor, a PTH inhibitor, a PTHLH inhibitor, a PRG analog, strontium ranelate, a DKK-1 inhibitor, a dual MET and VEGFR2 inhibitor, an estrogen receptor modulator, calcitonin, Radium-223, a CCR5 antagonist, a Src kinase inhibitor, a COX-2 inhibitor, an mTor inhibitor, and a cathepsin K inhibitor.

3. The method of claim 2 , wherein the bisphosphonate is zoledronic acid or clodronate.

4. The method of claim 1 , wherein the amplification of the c-MAF gene is determined by means of determining the amplification of the locus 16q22-q24.

5. The method of claim 1 , wherein the expression level is quantified by means of a quantitative polymerase chain reaction (PCR) or a DNA or RNA array or nucleotide hybridization technique.

6. The method according to claim 1 , wherein the amplification of the c-MAF gene is determined by means of in situ hybridization or PCR.

7. The method of claim 1 , wherein the bone metastasis is osteolytic metastasis.

8. The method according to claim 1 , wherein an increase of c-MAF expression level, copy number, or amplification compared to the predetermined reference level of c-MAF expression, copy number, or amplification indicates an increased risk of bone metastasis.

9. An in vitro method for designing a customized therapy for a subject having prostate cancer with bone metastasis which comprises

(i) quantifying the c-MAF gene expression level, copy number, or amplification in a bone metastatic tumor tissue sample of said subject;

(ii) comparing the expression level, copy number, or amplification obtained in step (i) with the expression level, copy number, or amplification of the c-MAF gene in a control sample, wherein an increase in the expression level, copy number, or amplification of the c-MAF gene in the tumor tissue sample is increased with respect to the expression level, copy number, or amplification of the c-MAF gene in the control sample, then said subject is susceptible to receive a therapy intended to prevent or inhibit bone degradation;

(iii) determining that the subject has an increase in the expression level, copy number or amplification of the c-MAF gene in the tumor tissue sample with respect to the expression level, copy number or amplification of the c-MAF gene in the control sample; and

(iv) administering a therapy intended to prevent or inhibit bone degradation.

10. The method of claim 9 , wherein the therapy intended to prevent or inhibit bone degradation is selected from the group consisting of a bisphosphonate, a RANKL inhibitor, a PTH inhibitor, a PTHLH inhibitor, a PRG analog, strontium ranelate, a DKK-1 inhibitor, a dual MET and VEGFR2 inhibitor, an estrogen receptor modulator, calcitonin, Radium-223, a CCR5 antagonist, a Src kinase inhibitor, a COX-2 inhibitor, an mTor inhibitor, and a cathepsin K inhibitor.

11. The method of claim 10 , wherein the bisphosphonate is zoledronic acid or clodronate.

12. The method of claim 9 , wherein the amplification of the c-MAF gene is determined by means of determining the amplification of the locus 16q22-q24.

13. The method of claim 9 , wherein the expression level is quantified by means of a quantitative polymerase chain reaction (PCR) or a DNA or RNA array or nucleotide hybridization technique.

14. The method according to claim 9 , wherein the amplification of the c-MAF gene is determined by means of in situ hybridization or PCR.

15. The method of claim 9 , wherein the bone metastasis is osteolytic metastasis.

16. The method according to claim 9 , wherein the increase of c-MAF expression is at least about 1.1 times, 1.2 times, 1.3 times, 1.4 times, 1.5 times, 2 times, 3 times, 4 times, 5 times, 10 times, 20 times, 30 times, 40 times, 50 times, 60 times, 70 times, 80 times, 90 times, 100 times or greater than the control sample.

17. A method for typing a sample of a subject suffering from prostate cancer, and treating said subject to avoid, inhibit, and/or treat bone degradation, comprising:

(i) quantifying the expression level of c-MAF in a prostate tumor sample;

(ii) typing said prostate tumor sample by comparing the quantified c-MAF expression level to a predetermined reference level of c-MAF expression level;

(iii) determining that the typing indicates a risk of bone metastasis in said subject; and

(iv) administering a therapeutically effective amount of clodronate or zoledronic acid to said subject.

18. The method of claim 17 , wherein the expression level of c-MAF is the expression level of c-MAF protein.

19. The method of claim 18 , wherein the expression level of the c-MAF protein is measured using Western blot, ELISA, immunohistochemistry or a protein array.

20. The method of claim 17 , wherein the bone metastasis is osteolytic metastasis.

21. The method according to claim 2 , wherein the estrogen receptor modulator inhibits the binding of estrogen to the estrogen receptor.

22. The method according to claim 2 , wherein the estrogen receptor modulator is selected from the group consisting of progestogen, estradiol, droloxifene, raloxifiene, lasofoxifene, TSE-424, tamoxifen, idoxifene, LY353381, LY117081, toremifene, fulvestrant, 4-[7-(2,2-dimethyl-1-oxopropoxy-4-methyl-2-[4-[2-(1-piperidinyl)ethoxy]phenyl]-2H-1-benzopyran-3-yl]-phenyl-2,2-dimethylpropanoate, and SH646.

23. The method according to claim 10 , wherein the estrogen receptor modulator inhibits the binding of estrogen to the estrogen receptor.

24. The method according to claim 10 , wherein the estrogen receptor modulator is selected from the group consisting of progestogen, estradiol, droloxifene, raloxifiene, lasofoxifene, TSE-424, tamoxifen, idoxifene, LY353381, LY117081, toremifene, fulvestrant, 4-[7-(2,2-dimethyl-1-oxopropoxy-4-methyl-2-4-2-(1-piperidinyl)ethoxy]phenyl]-2H-1-benzopyran-3-yl]-phenyl-2,2- dimethylpropanoate, and SH646.