Diagnostic tools and treatments for clear cell renal cell carcinoma

A method of diagnosing an elevated risk of recurrence of clear cell renal cell carcinoma in a subject and treating the subject for clear cell renal cell carcinoma, comprising:

• a. detecting and quantifying total copper content and Cu-COX complex in a sample of kidney tumor tissue or kidney tumor biopsy from said subject;
• b. diagnosing an elevated risk of recurrence of clear cell renal cell carcinoma for a subject with:
• i. a level of Cu-COX complex identified at a molecular mass range between 500 kDa-250 kDa is higher than 0.45 ng g−1 expressed as copper concentration;
• or
• ii. the copper content at a molecular mass fraction between 500 kDa-250 kDa is ≥20% of the total copper in the sample;
• and
• c. treating the subject diagnosed with an elevated risk of recurrence of clear cell renal cell carcinoma by administering a therapeutically effective amount of biguanides, metformin, phenformin, BAY-872243, IACS-010759, dihydroorotate dehydrogenase inhibitors, leflunomide, brequuinar, teriflunomide or combinations thereof to the subject.

A method of diagnosing an elevated risk of recurrence of clear cell renal cell carcinoma in a subject and treating the subject for clear cell renal cell carcinoma, comprising:

• a. detecting and quantifying total copper content and Cu-COX complex in a sample of kidney tumor tissue or kidney tumor biopsy from said subject;
• b. diagnosing an elevated risk of recurrence of clear cell renal cell carcinoma for a subject with:
• i. a level of Cu-COX complex identified at a molecular mass range between 500 kDa-250 kDa is higher than 0.45 ng g−1 expressed as copper concentration;
• or
• ii. the copper content at a molecular mass fraction between 500 kDa-250 kDa is ≥20% of the total copper in the sample;
• and
• c. treating the subject diagnosed with an elevated risk of recurrence of clear cell renal cell carcinoma by administering a therapeutically effective amount of copper chelators selected from the group consisting of D-penicillamine:
• (S)-2-amino-3-mercapto-3-methylbutanoic acid (DPA), Tetrathiomolybdate (TM), Trientine:
• triethylenetetramine dihydrochloride (TETA), 5,7-Dichloro-2 [(dimethylamino) methyl] quinolin-8-ol (PBT2), 2,3-Dimercaptosuccinic acid (DMSA) and combinations thereof to the subject.