Skip to main content
SpringerLink
Log in

Application of Multiplex Biomarker Approaches to Accelerate Drug Discovery and Development

  • Protocol
  • First Online:
Multiplex Biomarker Techniques

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1546))

Abstract

Multiplex biomarker tests are becoming an essential part of the drug development process. This chapter explores the role of biomarker-based tests as effective tools in improving preclinical research and clinical development, and the challenges that this presents. The potential of incorporating biomarkers in the clinical pipeline to improve decision making, accelerate drug development, improve translation, and reduce development costs is discussed. This chapter also discusses the latest biomarker technologies in use to make this possible and details the next steps that must undertaken to keep driving this process forwards.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 139.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Hughes JP, Rees S, Kalindjian SB, Philpott KL (2011) Principles of early drug discovery. Br J Pharmacol 162:1239–1249

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Giezen TJ, Mantel-Teeuwisse AK, Straus SM, Schellekens H, Leufkens HG, Egberts AC (2008) Safety-related regulatory actions for biologicals approved in the United States and the European Union. JAMA 300:1887–1896

    Article  CAS  PubMed  Google Scholar 

  3. McNaughton R, Huet G, Shakir S (2013) An investigation into drug products withdrawn from the EU market between 2002 and 2011 for safety reasons and the evidence used to support the decision-making. BMJ Open 4:e004221

    Article  Google Scholar 

  4. Onakpoya IJ, Heneghan CJ, Aronson JK (2016) Post-marketing withdrawal of 462 medicinal products because of adverse drug reactions: a systematic review of the world literature. BMC Med 14:10

    Article  PubMed  PubMed Central  Google Scholar 

  5. Rawson NS (2016) Drug safety: withdrawn medications are only part of the picture. BMC Med 14:28

    Article  PubMed  PubMed Central  Google Scholar 

  6. Ovens J (2006) Funding for accelerating drug development initiative critical. Nat Rev Drug Discov 5:271

    Article  CAS  Google Scholar 

  7. http://www.fda.gov/oc/initiatives/criticalpath/whitepaper.html

  8. Need AC, Motulsky AG, Goldstein DB (2005) Priorities and standards in pharmacogenetic research. Nat Genet 37:671–681

    Article  CAS  PubMed  Google Scholar 

  9. http://www.fda.gov/ohrms/dockets/ac/98/briefingbook/1998-3454B1_03_WL50.pdf

  10. Cohen JS (2006) Risks of troglitazone apparent before approval in USA. Diabetologia 49:1454–5145

    Article  CAS  PubMed  Google Scholar 

  11. Onakpoya IJ, Heneghan CJ, Aronson JK (2016) Worldwide withdrawal of medicinal products because of adverse drug reactions: a systematic review and analysis. Crit Rev Toxicol 3:1–13 [Epub ahead of print]

    Google Scholar 

  12. Marciante KD, Durda JP, Heckbert SR, Lumley T, Rice K, McKnight B et al (2011) Cerivastatin, genetic variants, and the risk of rhabdomyolysis. Pharmacogenet Genomics 21:280–288

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Choi S (2003) Nefazodone (Serzone) withdrawn because of hepatotoxicity. CMAJ 169:1187

    PubMed  PubMed Central  Google Scholar 

  14. Dogné JM, Hanson J, Supuran C, Pratico D (2006) Coxibs and cardiovascular side-effects: from light to shadow. Curr Pharm Des 12:971–975

    Article  PubMed  Google Scholar 

  15. http://www.bloomberg.com/news/articles/2013-07-18/merck-pays-23-million-to-end-vioxx-drug-purchase-suits

  16. Sheridan C (2006) TeGenero fiasco prompts regulatory rethink. Nat Biotechnol 24:475–476

    Article  CAS  PubMed  Google Scholar 

  17. Atkinson AJ, Colburn WA, DeGruttola VG, DeMets DL, Downing GJ, Hoth DF, Biomarkers Definitions Working Group et al (2001) Biomarkers and surrogate endpoints: preferred definitions and conceptual framework. Clin Pharmacol Ther 69:89–95

    Article  Google Scholar 

  18. Fulton RJ, McDade RL, Smith PL, Kienker LJ, Kettman JR Jr (1997) Advanced multiplexed analysis with the FlowMetrix system. Clin Chem 43:1749–1756

    Article  CAS  PubMed  Google Scholar 

  19. Anderson NL, Anderson NG (2002) The human plasma proteome: history, character, and diagnostic prospects. Mol Cell Proteomics 1:845–867

    Article  CAS  PubMed  Google Scholar 

  20. Link AJ, Eng J, Schieltz DM, Carmack E, Mize GJ, Morris DR et al (1999) Direct analysis of protein complexes using mass spectrometry. Nat Biotechnol 17:676–682

    Article  CAS  PubMed  Google Scholar 

  21. Griffin JL (2003) Metabonomics: NMR spectroscopy and pattern recognition analysis of body fluids and tissues for characterisation of xenobiotic toxicity and disease diagnosis. Curr Opin Chem Biol 7:648–654

    Article  CAS  PubMed  Google Scholar 

  22. Beckonert O, Keun HC, Ebbels TM, Bundy J, Holmes E, Lindon JC et al (2007) Metabolic profiling, metabolomic and metabonomic procedures for NMR spectroscopy of urine, plasma, serum and tissue extracts. Nat Protoc 2:2692–2703

    Article  CAS  PubMed  Google Scholar 

  23. Imming P, Sinning C, Meyer A (2006) Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov 5:821–834

    Article  CAS  PubMed  Google Scholar 

  24. Sioud M (2007) Main approaches to target discovery and validation. Methods Mol Biol 360:1–12

    CAS  PubMed  Google Scholar 

  25. Spaethling JM, Sanchez-Alavez M, Lee J, Xia FC, Dueck H, Wang W (2016) Single-cell transcriptomics and functional target validation of brown adipocytes show their complex roles in metabolic homeostasis. FASEB J 30:81–92

    Article  CAS  PubMed  Google Scholar 

  26. Rust S, Guillard S, Sachsenmeier K, Hay C, Davidson M, Karlsson A et al (2013) Combining phenotypic and proteomic approaches to identify membrane targets in a ‘triple negative’ breast cancer cell type. Mol Cancer 12:11

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Prosser GA, de Carvalho LP (2013) Metabolomics reveal d-alanine:d-alanine ligase as the target of d-cycloserine in Mycobacterium tuberculosis. ACS Med Chem Lett 4:1233–1237

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Amacher DE (2010) The discovery and development of proteomic safety biomarkers for the detection of drug-induced liver toxicity. Toxicol Appl Pharmacol 245:134–142

    Article  CAS  PubMed  Google Scholar 

  29. Meneses-Lorente G, Watt A, Salim K, Gaskell SJ, Muniappa N, Lawrence J et al (2006) Identification of early proteomic markers for hepatic steatosis. Chem Res Toxicol 19:986–998

    Article  CAS  PubMed  Google Scholar 

  30. Tang H, Panemangalore R, Yarde M, Zhang L, Cvijic ME (2016) 384-well multiplexed luminex cytokine assays for lead optimization. J Biomol Screen. pii: 1087057116644164. (Epub ahead of print)

    Google Scholar 

  31. Valet G (2006) Cytomics as a new potential for drug discovery. Drug Discov Today 11:785–791

    Article  CAS  PubMed  Google Scholar 

  32. Gale EA (2001) Lessons from the glitazones: a story of drug development. Lancet 357:1870–1875

    Article  CAS  PubMed  Google Scholar 

  33. Suter L, Schroeder S, Meyer K, Gautier JC, Amberg A, Wendt M et al (2010) EU framework 6 project: predictive toxicology (PredTox)--overview and outcome. Toxicol Appl Pharmacol 252:73–84

    Article  PubMed  CAS  Google Scholar 

  34. Afshari CA, Hamadeh HK, Bushel PR (2011) The evolution of bioinformatics in toxicology: advancing toxicogenomics. Toxicol Sci 120(S1):S225–S237

    Article  CAS  PubMed  Google Scholar 

  35. Bulera SJ, Eddy SM, Ferguson E, Jatkoe TA, Reindel JF, Bleavins MR et al (2001) RNA expression in the early characterization of hepatotoxicants in Wistar rats by high-density DNA microarrays. Hepatology 33:1239–1258

    Article  CAS  PubMed  Google Scholar 

  36. Waring JF, Ciurlionis R, Jolly RA, Heindel M, Ulrich RG (2001) Microarray analysis of hepatotoxins in vitro reveals a correlation between geneexpression profiles and mechanisms of toxicity. Toxicol Lett 120:359–368

    Article  CAS  PubMed  Google Scholar 

  37. Verret V, Namur J, Ghegediban SH, Wassef M, Moine L, Bonneau M et al (2013) Toxicity of doxorubicin on pig liver after chemoembolization with doxorubicin-loaded microspheres: a pilot DNA-microarrays and histology study. Cardiovasc Intervent Radiol 36:204–312

    Article  PubMed  Google Scholar 

  38. Tsuchiya H, Sato J, Tsuda H, Fujiwara Y, Yamada T, Fujimura A et al (2013) Serum amyloid A upsurge precedes standard biomarkers of hepatotoxicity in ritodrine-injected mice. Toxicology 305:79–88

    Article  CAS  PubMed  Google Scholar 

  39. Andersson U, Lindberg J, Wang S, Balasubramanian R, Marcusson-Ståhl M, Hannula M et al (2009) A systems biology approach to understanding elevated serum alanine transaminase levels in a clinical trial with ximelagatran. Biomarkers 14:572–586

    Article  CAS  PubMed  Google Scholar 

  40. Meneses-Lorente G, Guest PC, Lawrence J, Muniappa N, Knowles MR, Skynner HA et al (2004) A proteomic investigation of drug-induced steatosis in rat liver. Chem Res Toxicol 17:605–612

    Article  CAS  PubMed  Google Scholar 

  41. Killestein J, Polman CH (2011) Determinants of interferon β efficacy in patients with multiple sclerosis. Nat Rev Neurol 7:221–228

    Article  CAS  PubMed  Google Scholar 

  42. Gerger A, Labonte M, Lenz HJ (2011) Molecular predictors of response to antiangiogenesis therapies. Cancer J 17:134–141

    Article  CAS  PubMed  Google Scholar 

  43. Flood DG, Marek GJ, Williams M (2011) Developing predictive CSF biomarkers-A challenge critical to success in Alzheimer’s disease and neuropsychiatric translational medicine. Biochem Pharmacol 81:1422–1434

    Article  CAS  PubMed  Google Scholar 

  44. Kopetz S, Hoff PM, Morris JS, Wolff RA, Eng C, Glover KY et al (2010) Phase II trial of infusional fluorouracil, irinotecan, and bevacizumab for metastatic colorectal cancer: efficacy and circulating angiogenic biomarkers associated with therapeutic resistance. J Clin Oncol 28:453–459

    Article  CAS  PubMed  Google Scholar 

  45. Kempf K, Herder C, Erlund I, Kolb H, Martin S, Carstensen M et al (2010) Effects of coffee consumption on subclinical inflammation and other risk factors for type 2 diabetes: a clinical trial. Am J Clin Nutr 91:950–907

    Article  CAS  PubMed  Google Scholar 

  46. Miles DW, de Haas SL, Dirix LY, Romieu G, Chan A, Pivot X et al (2013) Biomarker results from the AVADO phase 3 trial of first-line bevacizumab plus docetaxel for HER2-negative metastatic breast cancer. Br J Cancer 108:1052–1060

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Poste G (2011) Bring on the biomarkers. Nature 469:156–157

    Article  CAS  PubMed  Google Scholar 

  48. Schumacher S, Nestler J, Otto T, Wegener M, Ehrentreich-Förster E, Michel D et al (2012) Highly-integrated lab-on-chip system for point-of-care multiparameter analysis. Lab Chip 12:464–473

    Article  CAS  PubMed  Google Scholar 

  49. Berg B, Cortazar B, Tseng D, Ozkan H, Feng S, Wei Q et al (2015) Cellphone-based hand-held micro-plate reader for point-of-care testing of enzyme-linked immunosorbent assays. ACS Nano 9:7857–7866

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge, CB2 3RA, UK

    Hassan Rahmoune

  2. Laboratory of Neuroproteomics, Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, SP, Brazil

    Paul C. Guest

Authors
  1. Hassan Rahmoune
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Paul C. Guest
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hassan Rahmoune .

Editor information

Editors and Affiliations

  1. Laboratory of Neuroproteomics, University of Campinas (UNICAMP), Campinas, Brazil

    Paul C. Guest

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer Science+Business Media LLC

About this protocol

Cite this protocol

Rahmoune, H., Guest, P.C. (2017). Application of Multiplex Biomarker Approaches to Accelerate Drug Discovery and Development. In: Guest, P.C. (eds) Multiplex Biomarker Techniques. Methods in Molecular Biology, vol 1546. Humana, New York, NY. https://doi.org/10.1007/978-1-4939-6730-8_1

Download citation

  • DOI: https://doi.org/10.1007/978-1-4939-6730-8_1

  • Published:

  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-4939-6729-2

  • Online ISBN: 978-1-4939-6730-8

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation