The failure of protein cancer biomarkers to reach the clinic: why, and what can be done to address the problem?

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 fusions^c	• Pending FDA approval
Separate indolent from aggressive prostate cancer	• PTEN loss^c • TMPRSS2-ERG fusions³	• More research necessary^e
Assess risk of malignancy of thyroid nodules with indeterminate results on biopsy	• HBME-1, Galectin-3 and CK19^d	• 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)

ISSN: 1741-7015