Method for the prognosis and treatment of cancer metastasis

An in vitro method for predicting the clinical outcome of a subject suffering bone metastasis from a triple negative or basal-like breast cancer and further treating said subject, which comprises

• i) quantifying the expression level of the c-MAF gene in a tumor sample of said subject, wherein the quantifying of the expression level comprises quantifying the messenger RNA (mRNA) of c-MAF, or a fragment of said mRNA, or quantifying the complementary DNA (cDNA) of c-MAF, or a fragment of said cDNA;
• ii) comparing the expression level obtained in step i) with a reference value,
• wherein increased expression level of said gene with respect to said reference value is indicative of a poor clinical outcome for said subject, wherein said subject has an increased expression level of said gene and is predicted to have a poor clinical outcome;
• and
• iii) administering to said subject a therapeutically effective amount of a c-MAF inhibitor, a therapy aiming to prevent and/or treat bone metastasis selected from the group consisting of an mTOR inhibitor, a Src Kinase inhibitor, a COX-2 inhibitor, a CCR-5 antagonist and/or Radium-223, and/or an agent capable of avoiding and/or preventing bone degradation to the subject if the subject is predicted to have a poor clinical outcome, and wherein the agent capable of avoiding and/or preventing the bone degradation is selected from the group consisting of a bisphosphonate, a RANKL inhibitor, PTH and PTHLH inhibitor or a PRG analog, strontium ranelate, a DKK-1 inhibitor, a dual MET and VEGFR2 inhibitor, an estrogen receptor modulator, calcitonin, and a cathepsin K inhibitor.

An in vitro method for designing a customized therapy for a subject suffering triple negative or basal-like breast cancer which comprises

• i) quantifying the c-MAF gene expression level in a tumor sample of said subject, wherein the quantifying of the c-MAF gene expression level comprises quantifying the messenger RNA (mRNA) of c-MAF, or a fragment of said mRNA, or quantifying the complementary DNA (cDNA) of c-MAF, or a fragment of said cDNA;
• ii) comparing the expression level obtained in i) with a reference value,
• wherein if the expression level is increased with respect to said reference value, then said subject is susceptible to receive a therapy aiming to prevent and/or treat bone metastasis and/or bone degradation, wherein said subject has an increased expression level with respect to said reference value and is susceptible to receive the therapy aiming to prevent and/or treat bone metastasis and/or bone degradation;
• and
• iii) administering to said subject a therapeutically effective amount of a c-MAF inhibitor, a therapy aiming to prevent and/or treat bone metastasis selected from the group consisting of an mTOR inhibitor, a Src Kinase inhibitor, a COX-2 inhibitor, a CCR-5 antagonist and/or Radium-223, and/or an agent capable of avoiding and/or preventing bone degradation to the subject if the subject is susceptible to receive the therapy aiming to prevent and/or treat bone metastasis and/or bone degradation, and wherein the agent capable of avoiding and/or preventing the bone degradation is selected from the group consisting of a bisphosphonate, a RANKL inhibitor, PTH and PTHLH inhibitor or a PRG analog, strontium ranelate, a DKK-1 inhibitor, a dual MET and VEGFR2 inhibitor, an estrogen receptor modulator, calcitonin, and a cathepsin K inhibitor.

An in vitro method for determining the risk of bone metastasis in a subject suffering triple negative or basal-like breast cancer and further treating said subject, which comprises quantifying the expression level of the c-MAF gene in a sample of a said subject, wherein the quantifying of the expression level comprises quantifying the messenger RNA (mRNA) of c-MAF, or a fragment of said mRNA, or quantifying the complementary DNA (cDNA) of c-MAF, or a fragment of said cDNA, wherein when the expression level of said gene is above an average value plus one standard deviation it is indicative of an increased risk of early bone metastasis or recurrence, and administering to said subject a therapeutically effective amount of a c-MAF inhibitor, a therapy aiming to prevent and/or treat bone metastasis selected from the group consisting of an mTOR inhibitor, a Src Kinase inhibitor, a COX-2 inhibitor, a CCR-5 antagonist and/or Radium-223, and/or an agent capable of avoiding and/or preventing bone degradation to the subject if the expression levels of said gene above the average value plus one standard deviation is indicative of an increased risk of early bone metastasis or recurrence, and wherein the agent capable of avoiding and/or preventing the bone degradation is selected from the group consisting of a bisphosphonate, a RANKL inhibitor, PTH and PTHLH inhibitor or a PRG analog, strontium ranelate, a DKK-1 inhibitor, a dual MET and VEGFR2 inhibitor, an estrogen receptor modulator, calcitonin, and a cathepsin K inhibitor, wherein the expression level of said gene in said subject is above the average value plus one standard deviation and is indicative of an increased risk of early bone metastasis or recurrence.