Personalized medicine has been presented in public and professional contexts in excessively optimistic tones. In the area of cancer what has become clear is the extraordinary heterogeneity and resilience of tumors in the face of numerous targeted therapies. This is the problem of cancer drug resistance. I summarize this problem in the first part of this essay. I then place this problem in the context of the larger political economic problem of escalating health care costs in both the EU and the US. In turn, that needs to be placed within an ethical context: How should we fairly distribute access to needed health care for an enormous range of health care needs when we have only limited resources (money) to meet virtually unlimited health care needs (cancer and everything else)? This is the problem of health care rationing. It is inescapable as a moral problem and requires a just resolution. Ultimately that resolution must be forged through a process of rational democratic deliberation.
References
[1]
Lemonick, M.D.; Park, A. New hope for cancer. TIME, 2001. Available online: http://www.time.com/time/magazine/article/0,9171,999978,00.html (accessed on 30 April 2013).
[2]
Fleck, L.M. Just Caring: Health Care Rationing and Democratic Deliberation; Oxford University Press: New York, NY, USA, 2009.
[3]
Garraway, L.A.; Jaenne, P.A. Circumventing cancer drug resistance in the era of personalized medicine. Cancer Discov. 2012, 2, 214–226, doi:10.1158/2159-8290.CD-12-0012.
[4]
Al-Lazikani, B.; Banerji, U.; Workman, P. Combinatorial drug therapy for cancer in the post-genomic era. Nat. Biotechnol. 2012, 30, 679–692, doi:10.1038/nbt.2284.
Misale, S.; Yaeger, R.; Hobor, S.; Scala, E.; Janakiraman, M.; Liska, D.; Valtorta, E.; Schiavo, R.; Buocarino, M.; Siravegna, G.; et al. Emergence of KRAS mutations and acquired resistance to anti-EGFR therapy in colorectal cancer. Nature 2012, 486, 532–536.
[7]
Gonalez, D.; Clarke, P.A.; Al-Lazikani, B.; workman, P. Personalized cancer medicine: Molecular diagnostics, predictive biomarkers, and drug resistance. Clin. Pharmacol. Ther. 2013, 93, 252–259, doi:10.1038/clpt.2012.237.
[8]
Fidler, I.J.; Hart, I.R. Biological diversity in metastatic neoplasms: Origins and implications. Science 1982, 217, 998–1003.
[9]
Heppner, G.H. Tumor heterogeneity. Cancer Res. 1984, 44, 2259–2265.
[10]
Gerlinger, M.; Rowan, A.J.; Horswell, S.; Math, M.; Larkin, J.; Endesfelder, D.; Gronroos, E.; Martinez, P.; Matthews, N.; Tarpey, P.; et al. Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. N. Engl. J. Med. 2012, 366, 883–892, doi:10.1056/NEJMoa1113205.
[11]
Raspe, E.; Decraene, C.; Berx, G. Gene expression profiling to dissect the complexity of cancer biology: Pitfalls and promise. Semin. Cancer Biol. 2012, 22, 250–260, doi:10.1016/j.semcancer.2012.02.011.
[12]
Longo, D.L. Tumor heterogeneity and personalized medicine. N. Engl. J. Med. 2012, 366, 956–957, doi:10.1056/NEJMe1200656.
[13]
Yap, T.A.; Omlin, A.; de Bono, J.S. Development of therapeutic combinations targeting major cancer signaling pathways. J. Clin. Oncol. 2013, 31, 1592–1605, doi:10.1200/JCO.2011.37.6418.
[14]
Lee, J.H.; Kim, D.G.; Bae, T.J.; Rho, K.; Kim, J.T.; Lee, J.J.; Jang, Y.; Kim, B.C.; Park, K.M.; Kim, S.; et al. CDA: Combinatorial drug discovery using transcriptional response modules. PLoS One 2012, 7, e42573, doi:10.1371/journal.pone.0042573.
[15]
Castano, Z.; Fillmore, C.M.; Kim, C.F.; McAllister, S.S. The bed and the bugs: Interactions between the tumor microenvironment and cancer stem cells. Semin. Cancer Biol. 2012, 22, 462–470, doi:10.1016/j.semcancer.2012.04.006.
[16]
Prasasya, S.D.; Tian, D.; Kreeger, P.K. Analysis of cancer signaling networks by systems biology to develop therapies. Semin. Cancer Biol. 2011, 21, 200–206, doi:10.1016/j.semcancer.2011.04.001.
[17]
The Cancer Genome Atlas Research Network. Genomic and epigenomic landscapes of adult de novo acute myeloid leukemia. N. Engl. J. Med. 2013, doi:10.1056/NEJMoa1301689.
[18]
Steensma, D.P. The beginning of the end of the beginning in cancer genomics. N. Engl. J. Med. 2013, doi:10.1056/NEJMe1303816.
[19]
Gatenby, R.A. A change of strategy in the war on cancer. Nature 2009, 459, 508–509, doi:10.1038/459508a.
[20]
Keehan, S.P.; Sisko, A.M.; Truffer, C.J.; Poisal, J.A.; Cuckler, G.A.; Madison, A.J.; Lisovitz, J.M.; Smith, S.D. National health spending projections through 2020: Economic recovery and reform drive faster spending growth. Health Aff. 2011, 30, 1594–1605, doi:10.1377/hlthaff.2011.0662.
[21]
Callahan, D. What Kind of Life: The Limits of Medical Progress; Simon & Schuster: New York, NY, USA, 1990. Chapter 2.
[22]
American Heart Association Statistics Committee. Heart disease and stroke statistics—2012 update: A report from the American Heart Association. Circulation 2012, 125, e2–e220, doi:10.1161/CIR.0b013e31823ac046.
[23]
Siegal, R.; Naishadham, D.; Jemal, A. Cancer statistics, 2013. CA Cancer J. Clin. 2013, 63, 11–30, doi:10.3322/caac.21166.
[24]
Wildavsky, A. Doing better and feeling worse: The political pathology of health policy. Daedalus 1977, 106, 105–123.
[25]
Fojo, T.; Parkinson, D.R. Biologically targeted cancer therapy and marginal benefits: Are we making too much of too little or are we achieving too little by giving too much? Clin. Cancer Res. 2010, 16, 5972–5980, doi:10.1158/1078-0432.CCR-10-1277.
[26]
MacReady, N. The climbing costs of cancer care. J. Natl. Cancer Inst. 2011, 103, 1433–1435, doi:10.1093/jnci/djr402.
[27]
Elkin, E.B.; Bach, P.B. Cancer’s next frontier: Addressing high and increasing costs. JAMA 2010, 303, 1086–1087, doi:10.1001/jama.2010.283.
[28]
Cohen, J.; Looney, W. What is the value of oncology medicines? Nat. Biotechnol. 2010, 28, 1160–1163, doi:10.1038/nbt1110-1160.
[29]
Fojo, T.; Grady, C. How much is life worth: Non-small cell lung cancer, and the $440 billion question. J. Natl. Cancer Inst. 2009, 101, 1044–1048, doi:10.1093/jnci/djp177.
[30]
Fleck, L.M. Last chance therapies: Can a just and caring society do health care rationing when life itself is at stake? Yale J. Health Policy Law Ethics 2002, 2, 255–298.
[31]
Daniels, N.; Sabin, J.E. Last chance therapies and managed care: Pluralism, fair procedures, and legitimacy. Hastings Cent. Rep. 1998, 28, 27–41, doi:10.2307/3527569.
[32]
Calabresi, G.; Bobbitt, P. Tragic Choices; W.W. Norton and Company: New York, NY, USA, 1978.
[33]
Bock, C.; Lengauer, T. Managing drug resistance in cancer: Lessons from HIV therapy. Nat. Rev. Cancer 2012, 12, 494–501, doi:10.1038/nrc3297.
[34]
Ubel, P. Why It’s Time for Health Care Rationing; MIT Press: Cambridge, MA, USA, 2000.
[35]
Callahan, D. False Hopes: Why America’s Quest for Perfect Health is a Recipe for Failure; Simon & Schuster: New York, NY, USA, 1998.
[36]
Daniels, N. Just Health: Meeting Health Needs Fairly; Cambridge University Press: New York, NY, USA, 2008.
[37]
Newdick, C. Who Should We Treat? Rights, Rationing, and Resources in the NHS, 2nd ed. ed.; Oxford University Press: Oxford, UK, 2005.
[38]
Engelhardt, H.T. The Foundations of Bioethics, 2nd ed. ed.; Oxford University Press: New York, NY, USA, 1996.
[39]
Institute of Medicine. America’s Uninsured Crisis: Consequences for Health and Health Care; The National Academies Press: Washington, D.C., USA, 2009.
[40]
Eddy, D.M. Clinical Decision Making: From Theory to Practice; Jones and Bartlett: Boston, MA, USA, 1996.
[41]
Veatch, R.M. The Foundations of Justice: Why the Retarded and the Rest of Us Have Claims to Equality; Oxford University Press: New York, NY, USA, 1986.
[42]
Harris, J. The Value of Life; Routledge& Kegan Paul: London, UK, 1985.
[43]
Dworkin, R. Sovereign Virtue: The Theory and Practice of Equality; Harvard University Press: Cambridge, MA, USA, 2000.
[44]
Christiano, T. The Constitution of Equality: Democratic Authority and Its Limits; Oxford University Press: New York, NY, USA, 2008.
[45]
Rawls, J. A Theory of Justice; Harvard University Press: Cambridge, MA, USA, 1971.
[46]
Konski, A. The war on cancer: Progress at what price? J. Clin. Oncol. 2011, 29, 1503–1504, doi:10.1200/JCO.2010.34.2758.
[47]
Sulmasy, D.P. Cancer care, money, and the value of life: Whose justice? Which rationality? J. Clin. Oncol. 2007, 25, 217–222, doi:10.1200/JCO.2006.08.0481.
[48]
Theriault, R.L. Health care costs: How do we decide value? When do we decide? How do we particularize the decisions? Oncologist 2012, 17, 157–159, doi:10.1634/theoncologist.2011-0371.
[49]
National Institute of Clinical Excellence. Available online: http://www.nice.org.uk/ (accessed on 7 May 2013).
[50]
Schneider, B.P.; Wang, M.; Radovich, M.; Sledge, G.W.; Badva, S.; Thor, A.; Flockhart, D.A.; Hancock, B.; Davidson, N.; Gralow, J.; et al. Association of vascular endothelial growth factor and vascular endothelial growth factor receptor-2 genetic polymorphisms with outcome in a trial of paclitaxel compared with paclitaxel plus bevacizumab in advanced breast cancer ECOG 2100. J. Clin. Oncol. 2008, 26, 4672–4678.
[51]
Sawyers, C.L. The cancer biomarker problem. Nature 2008, 452, 548–552, doi:10.1038/nature06913.
[52]
Johnston, F.; Pippen, J.; Pivot, X.; Lichinitser, M.; Sadeghi, S.; Dieras, V.; Gomez, V.L.; Romieu, G.; Manikhas, A.; Kennedy, M.J.; et al. Lapatinib combined with letrozole versus letrozole and placebo as first-line therapy for postmenopausal hormone receptor-positive metastatic breast cancer. J. Clin. Oncol. 2009, 27, 5538–5546, doi:10.1200/JCO.2009.23.3734.
[53]
Malvezzi, M.; Bertuccio, P.; Levi, F.; LaVecchia, C.; Negri, E. European cancer mortality predictions for the year 2013. Ann. Oncol. 2013, 24, 792–800, doi:10.1093/annonc/mdt010.
[54]
Mariotto, A.B.; Yabroff, K.R.; Shao, Y.; Feuer, E.J.; Brown, M.L. Projections of the cost of cancer care in the United States: 2010–2020. J. Natl. Cancer Inst. 2011, 103, 117–128, doi:10.1093/jnci/djq495.
[55]
New ￡50 million cancer fund already intellectually bankrupt. Lancet 2010, 376, 389, doi:10.1016/S0140-6736(10)61202-0.
[56]
Habermas, J. Between Facts and Norms: Contributions to a Discourse Theory of Law and Democracy; MIT Press: Cambridge, MA, USA, 1996.
