Table 2.
Niche applications of combinations of biomarkers with Food and Drug Administration approval or with potential in the future (unmet needs)
| Clinical application | Biomarkers | Status |
|---|---|---|
| Investigation of pelvic mass | • CA 125 and HE4 (+ ROMA)a • CA 125 and 7 proteomic markers (+ Danish-Index)b |
• FDA-approved (2011) • FDA-approved (2009) |
| Improve PSA specificity in screening | • Serum PSA and urine PCA-3 and TMPRSS2-ERG fusionsc | • Pending FDA approval |
| Separate indolent from aggressive prostate cancer | • PTEN lossc • TMPRSS2-ERG fusions3 |
• More research necessarye |
| Assess risk of malignancy of thyroid nodules with indeterminate results on biopsy | • HBME-1, Galectin-3 and CK19d | • More research necessary |
| Assess risk of malignancy of CT (± PET) imaging-identified indeterminate lung masses | • CEA, CYFRA 21-1, SCC, CA15.3, Pro-GRP, NSE | • More research necessary |
a See [9] for details; b see [10] for details; c see [12,15] for details; d see [16,17] for details. HBME-1 is an antimesothelial cell monoclonal antibody; e PCA-3 was approved by FDA (2012) to help determine the need for repeat prostatic biopsy in men who had a previous negative biopsy. See also [18]. CA: carbohydrate antigen; CT: computed tomography; CK19: cytokeratin 19; CYFRA 21-1: cytokeratin fragment 21-1; FDA: Food and Drug Administration; HBME-1: human bone marrow endothelial 1; HE4: human epididymis protein 4; NSE: neuron-specific enolase; PET: positron emission tomography; pro-GRP: pro-gastrin releasing peptide; PCA3: prostate cancer gene 3; PSA: prostate-specific antigen; PTEN: phosphatase and tensin homolog; ROMA: risk of ovarian malignancy algorithm; TMPRSS2-ERG: transmembrane protease, serine 2 (TMPRSS2) and v-ets erythroblastosis virus E26 oncogene homolog (avian) (ERG)