Top

Published in:

Open Access 01-12-2012 | Commentary

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

Author: Eleftherios P Diamandis

Published in: BMC Medicine | Issue 1/2012

Abstract

There is a plethora of published cancer biomarkers but the reality is that very few, if any, new circulating cancer biomarkers have entered the clinic in the last 30 years. I here try to explain this apparent oxymoron by classifying circulating cancer biomarkers into three categories: fraudulent reports (rare); true discoveries of biomarkers, that then fail to meet the demands of the clinic; and false discoveries, which represent artifactual biomarkers. I further provide examples of combinations of some known cancer biomarkers that can perform well in niche clinical applications, despite individually being not useful.

Available only for authorised users

Buchen L: Missing the mark. Why is it so hard to find a test to predict cancer?. Nature. 2011, 471: 428-432. 10.1038/471428a.CrossRefPubMed

Hanash SM: Why have protein biomarkers not reached the clinic?. Genome Med. 2011, 3: 66-10.1186/gm282.CrossRefPubMedPubMedCentral

Reich ES: Cancer trial errors revealed. Nature. 2011, 469: 139-140. 10.1038/469139a.CrossRef

Kantelhardt EJ, Vetter M, Schmidt M, Veyret C, Augustin D, Hanf V, Meisner C, Paepke D, Schmitt M, Sweep F, von Minckwitz G, Martin PM, Jaenicke F, Thomssen C, Harbeck N: Prospective evaluation of prognostic factors uPA/PAI-1 in node-negative breast cancer: phase III NNBC3-Europe trial (AGO, GBG, EORTC-PBG) comparing 6 × FEC versus 3 × FEC/3 × Docetaxel. BMC Cancer. 2011, 11: 140-10.1186/1471-2407-11-140.CrossRefPubMedPubMedCentral

Simon I, Zhuo S, Corral L, Diamandis EP, Sarno MJ, Wolfert RL, Kim NW: B7-h4 is a novel membrane-bound protein and a candidate serum and tissue biomarker for ovarian cancer. Cancer Res. 2006, 66: 1570-1575. 10.1158/0008-5472.CAN-04-3550.CrossRefPubMed

Cramer DW, Bast RC, Berg CD, Diamandis EP, Godwin AK, Hartge P, Lokshin AE, Lu KH, McIntosh MW, Mor G, Patriotis C, Pinsky PF, Thornquist MD, Scholler N, Skates SJ, Sluss PM, Srivastava S, Ward DC, Zhang Z, Zhu CS, Urban N: Ovarian cancer biomarker performance in prostate, lung, colorectal and ovarian cancer screening trial specimens. Cancer Prev Res. 2011, 4: 365-374. 10.1158/1940-6207.CAPR-10-0195.CrossRef

Diamandis EP, Hoffman BR, Sturgeon CM: National Academy of Clinical Biochemistry laboratory medicine practice guidelines for the use of tumor markers. Clin Chem. 2008, 54: 1935-1939. 10.1373/clinchem.2008.105494.CrossRefPubMed

Diamandis EP: Cancer biomarkers: can we turn recent failures into success?. J Natl Cancer Inst. 2010, 102: 1462-1467. 10.1093/jnci/djq306.CrossRefPubMedPubMedCentral

Molina R, Escudero JN, Augé JM, Filella X, Foj L, Torné A, Lejarcegui J, Pahisa J: HE4 a novel tumour marker for ovarian cancer: comparison with Ca125 and ROMA algorithm in patients with gynaecological diseases. Tumour Biol. 2011, 32: 1087-1095. 10.1007/s13277-011-0204-3.CrossRefPubMedPubMedCentral

10.

Hogdall C, Fung ET, Christensen IJ, Nedergaard L, Engelholm SA, Petri AL, Risum S, Lundvall L, Yip C, Pedersen AT, Hartwell D, Lomas L, Høgdall EV: A novel proteomic biomarker panel as a diagnostic tool for patients with ovarian cancer. Gynecol Oncol. 2011, 123: 308-313. 10.1016/j.ygyno.2011.07.018.CrossRefPubMed

11.

Molina R, Holdenrieder S, Auge JM, Schalhorn A, Hatz R, Stieber P: Diagnostic relevance of circulating biomarkers in patients with lung cancer. Cancer Biomark. 2010, 6: 163-178.PubMed

12.

de la Taille A, Irani J, Graefen A, Chun F, de Reijke T, Kil P, Gontero P, Mottaz A, Haese A: Clinical evaluation of the PCA3 assay in guiding initial biopsy decisions. J Urol. 2011, 185: 2119-2125. 10.1016/j.juro.2011.01.075.CrossRefPubMed

13.

Pepe MS, Feng Z, Janes H, Bossuyt PM, Potter JD: Pivotal evaluation of the accuracy of a biomarker used for classification or prediction: standards for study design. J Natl Cancer Inst. 2008, 100: 1432-1438. 10.1093/jnci/djn326.CrossRefPubMedPubMedCentral

14.

Ransohoff DF: Bias as a threat to the validity of cancer molecular-marker research. Nat Rev Cancer. 2005, 5: 142-149. 10.1038/nrc1550.CrossRefPubMed

15.

Sardana G, Dowell B, Diamandis EP: Emerging biomarkers for the diagnosis and prognosis of prostate cancer. Clin Chem. 2008, 54: 1951-1960. 10.1373/clinchem.2008.110668.CrossRefPubMed

16.

Fadda G, Rossi ED, Raffaelli M, Pontecorvi A, Sioletic S, Morassi F, Lombardi CP, Zannoni GF, Rindi G: Follicular thyroid neoplasms can be classified as low- and high-risk according to HBME-1 and Galectin-3 expression on liquid-based fine-needle cytology. Eur J Endocrinol. 2011, 165: 447-453. 10.1530/EJE-11-0181.CrossRefPubMed

17.

Nga ME, Lin GS, Soh CH, Kumarasinghe MP: HBME01 and CK19 are highly discriminatory in the cytological diagnosis of papillary thyroid carcinoma. Diagn Cytopathol. 2008, 36: 550-556. 10.1002/dc.20841.CrossRefPubMed

18.

Presner JR, Rubin MA, Wei JT, Chinnaiyan AM: Beyond PSA: the next generation of prostate cancer biomarkers. Sci Transl Med. 2012, 4: 127rv3-10.1126/scitranslmed.3003180.

The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1741-7015/10/87/prepub

Title: The failure of protein cancer biomarkers to reach the clinic: why, and what can be done to address the problem?
Author: Eleftherios P Diamandis
Publication date: 01-12-2012
Publisher: BioMed Central
Published in: BMC Medicine / Issue 1/2012
Electronic ISSN: 1741-7015
DOI: https://doi.org/10.1186/1741-7015-10-87

At a glance: The STEP trials

Springer Medicine

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

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 1/2012

Novel regulatory therapies for prevention of Graft-versus-host disease

Transcriptome changes in age-related macular degeneration

Is belief larger than fact: expectations, optimism and reality for translational stem cell research

Impact of evergreening on patients and health insurance: a meta analysis and reimbursement cost analysis of citalopram/escitalopram antidepressants

Crosstalk between HIV and hepatitis C virus during co-infection

Cost-effectiveness analysis for clinicians