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

doi:10.1186/1741-7015-10-87

. 2012 Aug 9:10:87.

doi: 10.1186/1741-7015-10-87.

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

Eleftherios P Diamandis¹

Affiliations

PMID: 22876833
PMCID: PMC3425158
DOI: 10.1186/1741-7015-10-87

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

Eleftherios P Diamandis. BMC Med. 2012.

. 2012 Aug 9:10:87.

doi: 10.1186/1741-7015-10-87.

Author

Eleftherios P Diamandis¹

Affiliation

¹ Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, ON, Canada. ediamandis@mtsinai.on.ca

PMID: 22876833
PMCID: PMC3425158
DOI: 10.1186/1741-7015-10-87

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.

PubMed Disclaimer

Figures

**Figure 1**
**Summary of reasons for biomarker failure to reach the clinic**. Fraud is a very rare reason for biomarker failures; most biomarkers represent true discoveries but their clinical characteristics are not good enough to be used at the clinic.

See this image and copyright information in PMC

Cited by

The Potential of Extracellular Matrix- and Integrin Adhesion Complex-Related Molecules for Prostate Cancer Biomarker Discovery.
Samaržija I. Samaržija I. Biomedicines. 2023 Dec 28;12(1):79. doi: 10.3390/biomedicines12010079. Biomedicines. 2023. PMID: 38255186 Free PMC article. Review.
An update on methods for detection of prognostic and predictive biomarkers in melanoma.
Adeuyan O, Gordon ER, Kenchappa D, Bracero Y, Singh A, Espinoza G, Geskin LJ, Saenger YM. Adeuyan O, et al. Front Cell Dev Biol. 2023 Oct 13;11:1290696. doi: 10.3389/fcell.2023.1290696. eCollection 2023. Front Cell Dev Biol. 2023. PMID: 37900283 Free PMC article. Review.
The Biomarker Toolkit - an evidence-based guideline to predict cancer biomarker success and guide development.
Savva KV, Kawka M, Vadhwana B, Penumaka R, Patton I, Khan K, Perrott C, Das S, Giot M, Mavroveli S, Hanna GB, Ni MZ, Peters CJ. Savva KV, et al. BMC Med. 2023 Oct 4;21(1):383. doi: 10.1186/s12916-023-03075-3. BMC Med. 2023. PMID: 37794461 Free PMC article.
Mass spectrometry-based proteomics as an emerging tool in clinical laboratories.
Birhanu AG. Birhanu AG. Clin Proteomics. 2023 Aug 26;20(1):32. doi: 10.1186/s12014-023-09424-x. Clin Proteomics. 2023. PMID: 37633929 Free PMC article. Review.
Somatic Copy Number Alteration in Circulating Tumor DNA for Monitoring of Pediatric Patients with Cancer.
Ruas JS, Silva FLT, Euzébio MF, Biazon TO, Daiggi CMM, Nava D, Franco MT, Cardinalli IA, Cassone AE, Pereira LH, Seidinger AL, Maschietto M, Jotta PY. Ruas JS, et al. Biomedicines. 2023 Apr 3;11(4):1082. doi: 10.3390/biomedicines11041082. Biomedicines. 2023. PMID: 37189699 Free PMC article.

See all "Cited by" articles

References

1. Buchen L. Missing the mark. Why is it so hard to find a test to predict cancer? Nature. 2011;471:428–432. doi: 10.1038/471428a. - DOI - PubMed
1. Hanash SM. Why have protein biomarkers not reached the clinic? Genome Med. 2011;3:66. doi: 10.1186/gm282. - DOI - PMC - PubMed
1. Reich ES. Cancer trial errors revealed. Nature. 2011;469:139–140. doi: 10.1038/469139a. - DOI - PubMed
1. 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. doi: 10.1186/1471-2407-11-140. - DOI - PMC - PubMed
1. 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. doi: 10.1158/0008-5472.CAN-04-3550. - DOI - PubMed

Publication types

Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Substances

Actions
Actions

LinkOut - more resources

Full Text Sources
Other Literature Sources
- The Lens - Patent Citations

[1] Buchen L. Missing the mark. Why is it so hard to find a test to predict cancer? Nature. 2011;471:428–432. doi: 10.1038/471428a. - DOI - PubMed

[2] Buchen L. Missing the mark. Why is it so hard to find a test to predict cancer? Nature. 2011;471:428–432. doi: 10.1038/471428a. - DOI - PubMed

[3] Hanash SM. Why have protein biomarkers not reached the clinic? Genome Med. 2011;3:66. doi: 10.1186/gm282. - DOI - PMC - PubMed

[4] Hanash SM. Why have protein biomarkers not reached the clinic? Genome Med. 2011;3:66. doi: 10.1186/gm282. - DOI - PMC - PubMed

[5] Reich ES. Cancer trial errors revealed. Nature. 2011;469:139–140. doi: 10.1038/469139a. - DOI - PubMed

[6] Reich ES. Cancer trial errors revealed. Nature. 2011;469:139–140. doi: 10.1038/469139a. - DOI - PubMed

[7] 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. doi: 10.1186/1471-2407-11-140. - DOI - PMC - PubMed

[8] 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. doi: 10.1186/1471-2407-11-140. - DOI - PMC - PubMed

[9] 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. doi: 10.1158/0008-5472.CAN-04-3550. - DOI - PubMed

[10] 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. doi: 10.1158/0008-5472.CAN-04-3550. - DOI - PubMed

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

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

Affiliation

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

Author

Affiliation

Abstract

Figures

Similar articles

Cited by

References

Publication types

MeSH terms

Substances

LinkOut - more resources

Full Text Sources

Other Literature Sources

Abstract

Figures

Similar articles

Cited by

References

Publication types

MeSH terms

Substances

Related information

LinkOut - more resources

Full Text Sources

Other Literature Sources