Skip to main content

Translation of Cancer Molecular Biomarkers: Ethical and Epistemological Issues

  • Chapter
  • First Online:

Abstract

The phenomenon of high cancer mortality has been the key factor in driving drug approval processes and health-care policies. In this paper, we discuss the inconsistencies of the genetic model of cancer as applied in the case of colorectal cancer (CRC). The result of relying on a genetic model of CRC is the approval of cancer drugs based on the inhibition of the epidermal growth factor receptor. The poor clinical performance of these drugs has prompted the use of a molecular biomarker to find the respondent patients. Due to the complexity of the cancer cell biological pathways, even the use of a molecular biomarker has not improved the clinical response of treated patients. Within the clinical uncertainty derived from the limited predictive value of a cancer molecular biomarker, we analyse the patient-doctor relationship. Beyond the challenge of communicating the medical uncertainty, many influences coming from the health-care system make the medical decisions biased. We analyse the ethical justification in using drugs that, at best, extend the patients’ survival for a few weeks, then we proceed to highlight the excessive cost of these drugs that create a problem for the allocation of resources for the whole society. We hold that a sensitive evaluation before the use of costly drugs for metastatic cancers must enter into the physician-patient relationship balancing the ethical concerns of the oncologist community and the need for the development of preventive policies.

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

Buying options

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   169.99
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

Learn about institutional subscriptions

Notes

  1. 1.

    Signal triggering molecule, binding to a target receptor.

References

  • Allegra CJ, Jessup JM, Sommerfield MR, Hamilton SR, Hammond EH, Hayes DF, McAllister PK, Morton RF, Schilsky RL (2009) American Society of Clinical Oncology provisional clinical opinion: testing for KRAS gene mutations in patients with metastatic colorectal carcinoma to predict response to anti-epidermal growth factor receptor monoclonal antibody therapy. J Clin Oncol 27(12):2091–2096

    Article  PubMed  Google Scholar 

  • Bardelli A, Siena S (2010) Molecular mechanisms of resistance to cetuximab and panitumumab in colorectal cancer. J Clin Oncol 28:1254–1261

    Article  PubMed  CAS  Google Scholar 

  • Barona JL (1997) Cancer patients and medical practice. Some historical and cultural considerations. Ann NY Acad Sci 809:17–29

    Article  PubMed  CAS  Google Scholar 

  • Bokemeyer C, Bondarenko I, Hartmann JT, de Braud F, Schuch G, Zubel A, Celik I, Schlichting M, Koralewski P (2011) Efficacy according to biomarker status of cetuximab plus FOLFOX-4 as first-line treatment for metastatic colorectal cancer: the OPUS study. Ann Oncol 22(7):1535–1546

    Article  PubMed  CAS  Google Scholar 

  • Braddock CH, Edwards KA, Hasenberg NH, Laidley TL, Levinson W (1999) Informed decision making in outpatient practice. Time to get back to basics. JAMA 282(24):2313–2320

    Article  PubMed  Google Scholar 

  • Callahan D (1976) Ethical responsibility in science in the face of uncertain consequences. Ann NY Acad Sci 265:1–12

    Article  PubMed  CAS  Google Scholar 

  • Fearon ER, Vogelstein B (1990) A genetic model for colorectal tumourigenesis. Cell 61:759–767

    Article  PubMed  CAS  Google Scholar 

  • Fojo T, Grady C (2009) How much is life worth: cetuximab, non-small cell lung cancer, and the $440 billion question. J Nat Cancer Inst 101(15):1044–1048

    Article  PubMed  Google Scholar 

  • Fraga MF, Esteller M (2007) Epigenetics and aging: the targets and the marks. Trends Genet 23:413–418

    Article  PubMed  CAS  Google Scholar 

  • Gafni A, Charles C (2009) The physician-patient encounter: an agency relationship? In: Edwards A, Elwyn G (eds) Shared decision-making in health care. Achieving evidence-based patient choice. Oxford University Press, New York, pp. 73–78

    Google Scholar 

  • Gawande A (2010) Letting go. What should medicine do when it can’t save your life? New Yorker Ann Med August 2, published online, Access date 02/12/2011

    Google Scholar 

  • Gilbert SF, Epel D (2009) Ecological developmental biology. Integrating epigenetics, medicine and evolution. Sinauer Associates, Sunderland

    Google Scholar 

  • Gravalos CJ, Cassinello J, Garcia-Alfonso P, Jimeno A (2010) Integration of panitumumab into the treatment of colorectal cancer. Crit Rev Oncol Hemat 74:16–26

    Article  Google Scholar 

  • Gschwind A, Fischer OM, Ullrich A (2004) The discovery of receptor tyrosine kinases: targets for cancer therapy. Nat Rev Cancer 4(5):361–370

    Article  PubMed  CAS  Google Scholar 

  • Hanahan D, Weinberg RA (2000) The hallmarks of cancer. Cell 100(1):57–70

    Article  PubMed  CAS  Google Scholar 

  • Issa JP, Ottaviano YL, Celano P, Hamilton SR, Davidson NE, Baylin SB (1994) Methylathion of the oestrogen receptor CpG islands links aging and neoplasia in human colon. Nat Genet 7:536–540

    Article  PubMed  CAS  Google Scholar 

  • Johnson RJ, Ning YM, Farrell A, Justice R, Keegan P, Pazdur R (2011) Accelerated approval of oncology products: the food and drug administration experience. J Nat Cancer Inst 103(8):616–617

    Article  Google Scholar 

  • Joshi SS, Ortiz S, Witherspoon JN, Rademaker A, West DP, Anderson R, Rosenbaum SE, Lecouture ME (2010) Effects of epidermal growth factor receptor inhibitor-induced dermatologic toxicities on quality of life. Cancer 116(16):3916–3923

    Article  PubMed  Google Scholar 

  • Nadler E, Eckert B, Neumann PJ (2006) Do oncologists believe new cancer drugs offer good value? Oncologist 11:90–95

    Article  PubMed  Google Scholar 

  • Peppercorn JM, Smith TJ, Helft PR, Debono DJ, Berry SR, Wollins DS, Hayes DM, Roen JH, Schnipper LE (2011) American society of clinical oncology statement: toward individualized care for patients with advanced cancer. J Clin Oncol 29(6):755–760

    Article  PubMed  Google Scholar 

  • Rapley T, May T (2009) Evidence and risk: the sociology of health care grappling with knowledge and uncertainty. In: Edwards A, Elwyn G (eds) Shared decision-making in health care. Achieving evidence-based patient choice. Oxford University Press, New York, pp. 53–58

    Google Scholar 

  • Sartore-Bianchi A, Bencardino K, Di Nicolantonio F, Pozzi F, Funaioli C, Gambi V, Arena S, Martini M, Lamba S, Cassingena A, Schiavo R, Bardelli A, Siena S (2010) Integrated molecular dissection of the epidermal growth factor receptor (EFGR) oncogenic pathway to predict response to EGFR-targeted monoclonal antibodies in metastatic colorectal cancer. Target Oncol 5:19–28

    Article  PubMed  Google Scholar 

  • Schrag D (2004) The price tag on progress-chemotherapy for colorectal cancer. New Engl J Med 351(4):317–319

    Article  PubMed  CAS  Google Scholar 

  • Starling N, Tilden D, White J, Cunningham D (2007) Cost-effectiveness analysis of cetuximab/irinotecan vs active/best supportive care for the treatment of metastatic colorectal cancer patients who have failed previous chemotherapy treatment. Br J Cancer 96:206–212

    Article  PubMed  CAS  Google Scholar 

  • Taylor BS, Ladanyi M (2011) Clinical cancer genomics: how soon is now? J Pathol 223:318–326

    Article  PubMed  Google Scholar 

  • Temel JS, Joseph MD, Muzikansky A, Gallagher ER, Admane S, Jackson VA, Dahlin CM, Blinderman CD, Jacobsen J, Pirl WF, Billings JA, Lynch TJ (2010) Early palliative care of patients with metastatic non-small-cell lung cancer. New Engl J Med 363:733–742

    Article  PubMed  CAS  Google Scholar 

  • Towle A, Godolphine W (2009) Education and training of health-care professionals. In: Edwards A, Elwyn G (eds) Shared decision-making in health care. Achieving evidence-based patient choice. Oxford University Press, New York, pp. 381–388

    Google Scholar 

  • Van Cutsem E, Peeters M, Siena S, Humblet Y, Hendlisz A, Neyns B, Canon J, Van Laethem J, Maurel J, Richardson G, Wolf M, Amado RG (2007) Open-label phase III trial of panitumumab plus best supportive care compared with best supportive care alone in patients with chemotherapy-refractory metastatic colorectal cancer. J Clin Oncol 25:1658–1664

    Article  PubMed  Google Scholar 

  • Van Cutsem E, Köhne CH, Hitre E, Zaluski J, Chang Chien CR, Makhson A, D’Haens G, Pintér T, Lim R, Bodoky G, Roh JK, Folprecht G, Ruff P, Stroh C, Tejpar S, Schlichting M, Nippgen J, Rougier P (2009) Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer. N Engl J Med 360(14):1408–1417

    Article  PubMed  Google Scholar 

  • Van Houdt WJ, Hoogwater FJ, de Bruijn MT, Emmink BL, Nijkamp MW, Raats DA, van der Groep P, van Diest P, Borel Rinkes IH, Kranenburg O (2010) Oncogenic KRAS desensitizes colorectal tumor cells to epidermal growth factor receptor inhibition and activation. Neoplasia 12(6):443–52

    Google Scholar 

  • Vincenzi B, Zoccoli A, Pantano F, Venditti O, Galluzzo S (2010) Cetuximab: from bench to bedside. Cur Cancer Drug Tar 10(1):80–95

    Article  CAS  Google Scholar 

  • Vogelstein B, Kinzler KW (2004) Cancer genes and the pathways they control. Nature Med 10(8):789–799

    Article  PubMed  CAS  Google Scholar 

  • Wegwarth O, Day RD, Gigerenzer G (2010) Decisions on pharmacogenomic tests in the USA and Germany. J Eval Clin Pract 17(2):228–235

    Article  PubMed  Google Scholar 

  • Woodcock J (2009) Chutes and ladders on the critical path: comparative effectiveness, product value, and the use of biomarkers in drug development. Int J Clin Pharmacol Ther 86(1):12–14

    Article  CAS  Google Scholar 

  • Yap TA, Sandhu SK, Workman P, Bono SJ (2010) Envisioning the future of early anticancer drug development. Nat Rev Cancer 10(7):514–523

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Flavio D’Abramo .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2012 Springer Basel AG

About this chapter

Cite this chapter

D’Abramo, F., Guastadisegni, C. (2012). Translation of Cancer Molecular Biomarkers: Ethical and Epistemological Issues. In: Schildmann, J., Sandow, V., Rauprich, O., Vollmann, J. (eds) Human Medical Research. Springer, Basel. https://doi.org/10.1007/978-3-0348-0390-8_14

Download citation

Publish with us

Policies and ethics