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

An in vitro method for designing a customized therapy for a subject with prostate cancer, comprising:

• (i) contacting a prostate tumor sample from the subject with an antibody to quantify c-MAF gene expression level or amplification, and
• (ii) comparing the expression level or amplification obtained in (i) with the expression level or amplification of the c-MAF gene in a control sample,
• wherein the antibody comprises a heavy chain CDR1 of SEQ ID NO:
• 21, a heavy chain CDR2 of SEQ ID NO:
• 22, a heavy chain CDR3 of SEQ ID NO:
• 23, a light chain CDR1 of SEQ ID NO:
• 18, a light chain CDR2 of SEQ ID NO:
• 19, and a light chain CDR3 of SEQ ID NO:
• 20,
• wherein if the expression level or amplification of the c-MAF gene in the tumor sample is increased with respect to the expression level or amplification of the c-MAF gene in the control sample, then said subject is susceptible to receive a therapy intended to prevent, inhibit and/or treat metastasis, relapse or recurrence of the cancer or a therapy intended to prevent or inhibit bone degradation.

A method for treating, inhibiting, reducing the risk of and/or preventing bone metastasis, relapse or recurrence from prostate cancer in a subject suffering prostate cancer, comprising:

• (i) contacting a prostate tumor sample from subject with an antibody to quantify c-MAF gene expression level or amplification,
• (ii) comparing the expression level or amplification obtained in (i) with the expression level or amplification of the c-MAF gene in a control sample, wherein if the expression level or amplification or the c-MAF gene in the tumor sample is increased with respect to the expression level or amplification of the c-MAF gene in the control sample, then the subject is susceptible to receive a c-MAF inhibitory agent and/or a therapy intended to prevent or inhibit bone degradation, and
• (iii) administering a c-MAF inhibitory agent to the subject selected from the group consisting of:
• a c-MAF specific siRNA, a c-MAF specific antisense oligonucleotide, a c-MAF specific ribozyme, a c-MAF inhibitory antibody or nanobody, a dominant negative c-MAF variant, a compound from Table 1 or from Table 2, catalytic RNAs, DNA enzymes, inhibitory antibodies, inhibitory peptides, a c-MAF specific small molecule, a c-MAF specific antibody, a c-MAF specific antibody-like molecule, a c-MAF specific structurally constrained (cyclical) peptide, a c-MAF specific stapled peptide, and a c-MAF specific alphabody, and/or
• administering a therapy intended to prevent or inhibit bone degradation to the subject selected from the group consisting of:
• a bisphosphonate, a RANKL, inhibitor, a PTH or PTHLH inhibitor, a PRG analog, strontium ranelate, a DKK-1 inhibitor, a dual MET and VEGFR2 inhibitor, an estrogen receptor modulator, an EGFR inhibitor, calcitonin, Radium-223, and a cathepsin K inhibitor,
• wherein the antibody comprises a heavy chain CDR1 of SEQ ID NO:
• 21, a heavy chain CDR2 of SEQ ID NO:
• 22, a heavy chain CDR3 of SEQ ID NO:
• 23, a light chain CDR1 of SEQ ID NO:
• 18, a light chain CDR2 of SEQ ID NO:
• 19, and a light chain CDR3 of SEQ ID NO:
• 20.

A kit for predicting bone metastasis, relapse or recurrence of a prostate cancer in a subject suffering from said cancer or for determining a therapy for a subject suffering prostate cancer, comprising:

• a) means for quantifying the expression level of c-MAF in a tumor sample of said subject;
• b) means for comparing the quantified level of expression of c-MAF in said sample to a reference c-MAF expression level, and, optionally,
• c) means for determining a therapy for preventing, inhibiting and/or reducing bone metastasis, relapse or recurrence in said subject based on the comparison of the quantified expression level to the reference c-MAF expression level,
• wherein the means for quantifying the expression level of c-MAF is an antibody comprising a heavy chain CDR1 of SEQ. ID NO:
• 21, a heavy chain CDR2 of SEQ ID NO:
• 22, a heavy chain CDR3 of SEQ ID NO:
• 23, a light chain CDR1 of SEQ 1D NO:
• 18, a light chain CDR2 of SEQ ID NO:
• 19, and a light chain CDR3 of SEQ ID NO:
• 20.

An in vitro method for typing a sample of a subject suffering from prostate cancer, comprising:

• (i) providing a tumor sample from said subject;
• (ii) contacting lwith an antibody to quantify the expression level or amplification of c-MAF;
• (iii) typing said sample by comparing the quantified expression level or amplification of c-MAF to a predetermined reference level of c-MAF expression or amplification;
• wherein the antibody comprises a heavy chain CDR1 of SEQ ID NO:
• 21, a heavy chain CDR2 of SEQ ID NO:
• 22, a heavy chain CDR3 of SEQ ID NO:
• 23, a light chain CDR1 of SEQ ID NO:
• 18, a light chain CDR2 of SEQ ID NO:
• 19, and a light chain CDR3 of SEQ ID NO:
• 20,
• wherein said typing provides prognostic information related to the risk of bone metastasis, relapse or recurrence in said subject.

A method of classifying a subject suffering from prostate cancer into a cohort, comprising:

• a) contacting a prostate tumor sample from the subject with an antibody to quantify c-MAF gene expression level or amplification;
• b) comparing the expression level or amplification of c-MAF in said sample to a predetermined reference level of c-MAF expression or amplification;
• and
• c) classifying said subject into a cohort based on said expression level or amplification of c-MAF in said sample,
• wherein the antibody comprises a heavy chain CDR1 of SEQ ID NO:
• 21, a heavy chain CDR2 of SEQ ID NO:
• 22, a heavy chain CDR3 of SEQ ID NO:
• 23, a light chain CDR1 of SEQ ID NO:
• 18, a light chain CDR2 of SEQ ID NO:
• 19, and a light chain CDR3 of SEQ ID NO:
• 20.