Researchers at UCLA and their collaborators are developing a platform that will allow clinicians to diagnose a prostate cancer patient by evaluating the phosphoproteome from tissue obtained by biopsy. In addition to diagnosis, this method provides information about kinase activation that a clinician can use for treatment decisions.
Early stage prostate cancer is dependent on androgens for survival. Men diagnosed with aggressive prostate cancer initially respond well to anti-androgen therapies but eventually develop a more drug resistant form of the disease. In addition, all prostate cancer patients are essentially treated with the same regimen and there are currently no subtypes to stratify patients for therapeutic purposes. Therefore, the development of new diagnostic biomarkers that predict disease progression or new companion biomarkers that stratify patients for effective personalized therapy are urgently needed.
Researchers at UCLA along with their collaborators are developing a method that will allow clinicians to diagnose prostate cancer by evaluating the phosphoproteome, or phosphorylated proteome, from patient tissues obtained by biopsy. In order to rapidly transition this method into the clinic, the inventors have optimized the selected ion monitoring (SIM) mass spectrometry technique to screen a patient’s phosphoproteome accurately and sensitively. In addition to diagnostics, the proposed prostate cancer phosphoproteome biomarkers can also guide clinicians through treatment decisions by identifying activated kinases. Thus far, the inventors have shown that specific kinases are activated in metastatic castration resistant prostate cancer (CRPC) but not normal tissue or less advanced stages of disease. The advantage of using the phosphopeptides they have selected is that the biomarkers are targets of FDA approved drugs or late-stage clinical trials, allowing the results of their approach to be moved to the clinic very quickly.