Médecine de précision et médecine des systèmes : La médecine personnalisée se trompe-t-elle de cible ?
DOI :
https://doi.org/10.20416/lsrsps.v4i2.983Mots-clés :
médecine personnalisée, médecine de précision, médecine des systèmes, thérapie ciblée, addiction oncogénique, modèles explicatifs du cancerRésumé
Le terme de médecine personnalisée peut désigner indifféremment la médecine de précision et la médecine des systèmes. L’objectif de cet article est d’analyser les rapports entre ces deux faces de la médecine personnalisée, au prisme de l’histoire du développement des thérapies ciblées. Les thérapies ciblées ont été développées dans le cadre de la médecine de précision, en s’appuyant sur le concept d’addiction oncogénique et sur l’idée qu’à chaque biomarqueur permettant d’identifier un sous-type de cancer correspondrait un médicament précis. Ce modèle a permis des succès thérapeutiques remarquables, mais a également rencontré des limites, notamment avec l’apparition des résistances aux thérapies ciblées. Pour mieux comprendre les raisons de ces limites, il me semble qu’il faut justement se tourner plutôt vers la médecine des systèmes. Je soutiens en particulier que cette dernière repose sur des concepts de robustesse et de redondance fonctionnelle, qui nous permettent de comprendre en quoi l’apparition des phénomènes de résistance est une conséquence inéluctable et non transitoire du développement des thérapies ciblées. Il s’agit donc de montrer comment la médecine des systèmes permet de penser différemment les stratégies thérapeutiques dans la prise en charge du cancer et l’évolution future de la médecine de précision.
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INCa. 2016. Les thérapies ciblées dans le traitement du cancer en 2015 / Etats des lieux et enjeux, appui à la décision.
KAWAMURA, Takahisa, et al. 2016. Rebiopsy for patients with non-small-cell lung cancer after epidermal growth factor receptor-tyrosine kinase inhibitor failure. Cancer Science, 107(7), 1001‑1005.
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KITANO, Hiroaki. 2002. Systems Biology: A Brief Overview. Science, 295(5560), 1662‑1664.
https://doi.org/10.1126/science.1069492
KITANO, Hiroaki. 2004. Biological robustness. Nature reviews Genetics,5(11), 826‑837.
https://doi.org/10.1038/nrg1471
KNUDSON, Albert G. 1971. Mutation and cancer: statistical study of retinoblastoma. Proceedings of the National Academy of Sciences of the United States of America, 68(4), 820‑823.
https://doi.org/10.1073/pnas.68.4.820
LE TOURNEAU, Christophe. 2012. Edito. La Lettre du Cancérologue, XXI (6), 284-288.
LI, Tianhong, KUNG, Hsing-Jien, MACK, Philip C., GANDARA, David R. 2013. Genotyping and Genomic Profiling of Non–Small-Cell Lung Cancer: Implications for Current and Future Therapies. Journal of Clinical Oncology, 31(8), 1039‑1049.
https://doi.org/10.1200/JCO.2012.45.3753
LUO, Ji, SOLIMINI, Nicole L., ELLEDGE, Stephen J. 2009. Principles of Cancer Therapy: Oncogene and Non-oncogene Addiction. Cell, 136(5), 823‑837.
https://doi.org/10.1016/j.cell.2009.02.024
MARX, Vivien. 2014. Cancer genomes: discerning drivers from passengers. Nature methods, 11(4), 375.
https://doi.org/10.1038/nmeth.2891
MOLINA-VILA, Miguel A., et al. 2016. Liquid Biopsy in Non-Small Cell Lung Cancer. Frontiers in Medicine, 3.
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National Research Council (U.S.) (éd.). 2011. Toward precision medicine: building a knowledge network for biomedical research and a new taxonomy of disease. Washington D.C. : National Academies Press.
PAGLIARINI, Raymond, SHAO, Wenlin, SELLERS, William. R. 2015. Oncogene addiction: pathways of therapeutic response, resistance, and road maps toward a cure. EMBO reports, 16(3), 280‑296.
https://doi.org/10.15252/embr.201439949
POKORSKA-BOCCI, Anna, et al. 2014. “Personalized medicine”: what’s in a name?. Personalized Medicine, 11(2), 197‑210.
https://doi.org/10.2217/pme.13.107
RAYMOND, Eric. 2014. Le concept de cible en cancérologie. Paris: John Euro Libbey Text.
RECK, Martin, et al. 2016. Pembrolizumab versus Chemotherapy for PD-L1-Positive Non-Small-Cell Lung Cancer. New England Journal of Medicine, 375(19), 1823‑1833.
https://doi.org/10.1056/NEJMoa1606774
SCAGLIOTTI, Giorgio Vittorio, et al. 2008. Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage non-small-cell lung cancer. Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology, 26(21), 3543‑3551.
https://doi.org/10.1200/JCO.2007.15.0375
SHARMA, Sreenath V., SETTLEMAN, Jeffrey. 2007. Oncogene addiction: setting the stage for molecularly targeted cancer therapy. Genes & Development, 21(24), 3214‑3231.
https://doi.org/10.1101/gad.1609907
SILVERMAN, E. K., LOSCALZO, Joseph. 2012. Network medicine approaches to the genetics of complex diseases. Discovery medicine, 14(75), 143-52.
SWAIN, Sandra M., et al. 2015. Pertuzumab, Trastuzumab, and Docetaxel in HER2-Positive Metastatic Breast Cancer. New England Journal of Medicine, 372(8), 724‑734.
https://doi.org/10.1056/NEJMoa1413513
SWANTON, Charles, GOVINDAN, Ramaswamy. 2016. Clinical Implications of Genomic Discoveries in Lung Cancer. New England Journal of Medicine, 374(19), 1864‑1873.
https://doi.org/10.1056/NEJMra1504688
TAN, Aik-Choon, VYSE, Simon, HUANG, Paul H. 2017. Exploiting receptor tyrosine kinase co-activation for cancer therapy. Drug Discovery Today, 22(1), 72‑84.
https://doi.org/10.1016/j.drudis.2016.07.010
TONON, Giovanni. 2008. From oncogene to network addiction: the new frontier of cancer genomics and therapeutics. Future Oncology, 4(4), 569‑577.
https://doi.org/10.2217/14796694.4.4.569
TORTI, Davide, TRUSOLINO, Livio. 2011. Oncogene addiction as a foundational rationale for targeted anti-cancer therapy: promises and perils. EMBO Molecular Medicine, 3(11), 623‑636.
https://doi.org/10.1002/emmm.201100176
TURNER, Nicholas C., REIS-FILHO, Jorge S. 2012. Genetic heterogeneity and cancer drug resistance. The Lancet Oncology, 13(4), e178‑e185.
https://doi.org/10.1016/S1470-2045(11)70335-7
VOGT, Henrik, ULVESTAD, Elling, ERIKSEN, Thor Eirik, GETZ, Linn. 2014. Getting personal: can systems medicine integrate scientific and humanistic conceptions of the patient?: Systems medicine and the patient. Journal of Evaluation in Clinical Practice, 20(6), 942‑952.
https://doi.org/10.1111/jep.12251
WEINSTEIN, I. Bernard. 2002. CANCER: Enhanced: Addiction to Oncogenes-the Achilles Heal of Cancer. Science, 297(5578), 63‑64.
https://doi.org/10.1126/science.1073096
WEINSTEIN, I. Bernard, JOE, Andrew K. 2006. Mechanisms of Disease: oncogene addiction-a rationale for molecular targeting in cancer therapy. Nature Clinical Practice Oncology, 3(8), 448‑457.
https://doi.org/10.1038/ncponc0558
WEST, Lisandra, et al. 2012. A Novel Classification of Lung Cancer into Molecular Subtypes. PLoS ONE, 7(2).
https://doi.org/10.1371/journal.pone.0031906
WOLKENHAUER, Olaf, GREEN, Sara. 2013. The search for organizing principles as a cure against reductionism in systems medicine. The FEBS journal, 280 (23), 5938‑5948.
https://doi.org/10.1111/febs.12311
https://doi.org/10.1002/wsbm.1173
AUFFRAY, Charles, CHEN, Zhu, HOOD, Leroy. 2009. Systems medicine: the future of medical genomics and healthcare. Genome Medicine, 1(1), 2-3.
https://doi.org/10.1186/gm2
BARABÁSI, Albert-Laszlo, GULBAHCE, Natali, LOSCALZO, Joseph. 2011. Network medicine: a network-based approach to human disease. Nature Reviews Genetics, 12 (1) 56‑68.
https://doi.org/10.1038/nrg2918
BARABÁSI, Albert-Laszlo, OLTVAI, Zoltan. N. 2004. Network biology: understanding the cell’s functional organization. Nature Reviews Genetics, 5, 101‑113.
https://doi.org/10.1038/nrg1272
BARLESI, Fabrice, et al. 2016. Routine molecular profiling of patients with advanced non-small-cell lung cancer: results of a 1-year nationwide programme of the French Cooperative Thoracic Intergroup (IFCT). The Lancet, 387 (10026), 1415‑1426.
https://doi.org/10.1016/S0140-6736(16)00004-0
de BONO, Johann S., ASHWORTH, Alan. 2010. Translating cancer research into targeted therapeutics. Nature, 467 (7315), 543‑549.
https://doi.org/10.1038/nature09339
BOSC, Cecile, et al. 2015. Rebiopsy during disease progression in patients treated by TKI for oncogene-addicted NSCLC. Targeted Oncology, 10(2), 247‑253.
https://doi.org/10.1007/s11523-014-0332-y
BRAHMER, Julie, et al. 2015. Nivolumab versus Docetaxel in Advanced Squamous-Cell Non-Small-Cell Lung Cancer. The New England Journal of Medicine, 373(2), 123‑135.
https://doi.org/10.1056/NEJMoa1504627
CARR, T. Hedley, et al. 2016. Defining actionable mutations for oncology therapeutic development. Nature Reviews Cancer, 16 (5), 319‑329.
https://doi.org/10.1038/nrc.2016.35
CATENACCI, Daniel V.T. 2015. Next-generation clinical trials: Novel strategies to address the challenge of tumor molecular heterogeneity. Molecular Oncology, 9 (5), 967‑996.
https://doi.org/10.1016/j.molonc.2014.09.011
CHANG, John W. C., et al. 2015. Early radiographic response to epidermal growth factor receptor-tyrosine kinase inhibitor in non-small cell lung cancer patients with epidermal growth factor receptor mutations: A prospective study. Biomedical Journal, 38(3), 221‑228.
https://doi.org/10.4103/2319-4170.138320
COX, Adrienne D., DER, Channing J. 2010. Ras history: The saga continues. Small GTPases, 1(1), 2‑27.
https://doi.org/10.4161/sgtp.1.1.12178
DANG, Chi V., REDDY, E. Premkumar, SHOKAT, Kevan M., SOUCEK, Laura. 2017. Drugging the “undruggable” cancer targets. Nature Reviews Cancer, 17(8), 502‑508.
https://doi.org/10.1038/nrc.2017.36
DARRASON, Marie. 2014. Y a-t-il une théorie génétique de la maladie ?. Thèse de doctorat. Université Paris 1 Panthéon-Sorbonne.
DE GRANDIS, Giovanni, HALGUNSET, Vidar. 2016. Conceptual and terminological confusion around personalised medicine: a coping strategy. BMC Medical Ethics, 17(1).
https://doi.org/10.1186/s12910-016-0122-4
DURUISSEAUX, Michaël, et al. 2017. Overall survival with crizotinib and next-generation ALK inhibitors in ALK-positive non-small-cell lung cancer (IFCT-1302 CLINALK): a French nationwide cohort retrospective study. Oncotarget, 8(13), 21903-21917.
https://doi.org/10.18632/oncotarget.15746
ERLER, Janine T., LINDING, Rune. 2010. Network-based drugs and biomarkers. The Journal of pathology, 220(2), 290‑296.
https://doi.org/10.1002/path.2646
FRANTZ, Simon. 2005. Drug discovery: playing dirty. Nature, 437(7061), 942–943.
https://doi.org/10.1038/437942a
FRIBOULET, Luc, et al. 2014. The ALK inhibitor ceritinib overcomes crizotinib resistance in non-small cell lung cancer. Cancer Discovery, 4(6), 662‑673.
https://doi.org/10.1158/2159-8290.CD-13-0846
GROENENDIJK, Floris H., BERNARDS, René. 2014. Drug resistance to targeted therapies: Déjà vu all over again. Molecular Oncology, 8(6), 1067‑1083.
https://doi.org/10.1016/j.molonc.2014.05.004
HANAHAN, Douglas et WEINBERG, Robert A. 2011. Hallmarks of cancer: the next generation. Cell, 144(5), 646‑674.
https://doi.org/10.1016/j.cell.2011.02.013
HAS. 2014. Guide méthodologique : Test compagnon associé à une thérapie ciblée - Annexe scientifique.
HOBBS, G. Aaron, WITTINGHOFER, Alfred, DER, Channing J. 2016. Selective Targeting of the KRAS G12C Mutant: Kicking KRAS When It’s Down. Cancer Cell, 29(3), 251‑253.
https://doi.org/10.1016/j.ccell.2016.02.015
HOOD, Leroy, FLORES, Mauricio. 2012. A Personal View on Systems Medicine and the Emergence of Proactive P4 Medicine: Predictive, Preventive, Personalized and Participatory. New Biotechnology, 29(6), 613‑624.
https://doi.org/10.1016/j.nbt.2012.03.004
INCa. 2016. Les thérapies ciblées dans le traitement du cancer en 2015 / Etats des lieux et enjeux, appui à la décision.
KAWAMURA, Takahisa, et al. 2016. Rebiopsy for patients with non-small-cell lung cancer after epidermal growth factor receptor-tyrosine kinase inhibitor failure. Cancer Science, 107(7), 1001‑1005.
https://doi.org/10.1111/cas.12963
KITANO, Hiroaki. 2002. Systems Biology: A Brief Overview. Science, 295(5560), 1662‑1664.
https://doi.org/10.1126/science.1069492
KITANO, Hiroaki. 2004. Biological robustness. Nature reviews Genetics,5(11), 826‑837.
https://doi.org/10.1038/nrg1471
KNUDSON, Albert G. 1971. Mutation and cancer: statistical study of retinoblastoma. Proceedings of the National Academy of Sciences of the United States of America, 68(4), 820‑823.
https://doi.org/10.1073/pnas.68.4.820
LE TOURNEAU, Christophe. 2012. Edito. La Lettre du Cancérologue, XXI (6), 284-288.
LI, Tianhong, KUNG, Hsing-Jien, MACK, Philip C., GANDARA, David R. 2013. Genotyping and Genomic Profiling of Non–Small-Cell Lung Cancer: Implications for Current and Future Therapies. Journal of Clinical Oncology, 31(8), 1039‑1049.
https://doi.org/10.1200/JCO.2012.45.3753
LUO, Ji, SOLIMINI, Nicole L., ELLEDGE, Stephen J. 2009. Principles of Cancer Therapy: Oncogene and Non-oncogene Addiction. Cell, 136(5), 823‑837.
https://doi.org/10.1016/j.cell.2009.02.024
MARX, Vivien. 2014. Cancer genomes: discerning drivers from passengers. Nature methods, 11(4), 375.
https://doi.org/10.1038/nmeth.2891
MOLINA-VILA, Miguel A., et al. 2016. Liquid Biopsy in Non-Small Cell Lung Cancer. Frontiers in Medicine, 3.
https://doi.org/10.3389/fmed.2016.00069
National Research Council (U.S.) (éd.). 2011. Toward precision medicine: building a knowledge network for biomedical research and a new taxonomy of disease. Washington D.C. : National Academies Press.
PAGLIARINI, Raymond, SHAO, Wenlin, SELLERS, William. R. 2015. Oncogene addiction: pathways of therapeutic response, resistance, and road maps toward a cure. EMBO reports, 16(3), 280‑296.
https://doi.org/10.15252/embr.201439949
POKORSKA-BOCCI, Anna, et al. 2014. “Personalized medicine”: what’s in a name?. Personalized Medicine, 11(2), 197‑210.
https://doi.org/10.2217/pme.13.107
RAYMOND, Eric. 2014. Le concept de cible en cancérologie. Paris: John Euro Libbey Text.
RECK, Martin, et al. 2016. Pembrolizumab versus Chemotherapy for PD-L1-Positive Non-Small-Cell Lung Cancer. New England Journal of Medicine, 375(19), 1823‑1833.
https://doi.org/10.1056/NEJMoa1606774
SCAGLIOTTI, Giorgio Vittorio, et al. 2008. Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage non-small-cell lung cancer. Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology, 26(21), 3543‑3551.
https://doi.org/10.1200/JCO.2007.15.0375
SHARMA, Sreenath V., SETTLEMAN, Jeffrey. 2007. Oncogene addiction: setting the stage for molecularly targeted cancer therapy. Genes & Development, 21(24), 3214‑3231.
https://doi.org/10.1101/gad.1609907
SILVERMAN, E. K., LOSCALZO, Joseph. 2012. Network medicine approaches to the genetics of complex diseases. Discovery medicine, 14(75), 143-52.
SWAIN, Sandra M., et al. 2015. Pertuzumab, Trastuzumab, and Docetaxel in HER2-Positive Metastatic Breast Cancer. New England Journal of Medicine, 372(8), 724‑734.
https://doi.org/10.1056/NEJMoa1413513
SWANTON, Charles, GOVINDAN, Ramaswamy. 2016. Clinical Implications of Genomic Discoveries in Lung Cancer. New England Journal of Medicine, 374(19), 1864‑1873.
https://doi.org/10.1056/NEJMra1504688
TAN, Aik-Choon, VYSE, Simon, HUANG, Paul H. 2017. Exploiting receptor tyrosine kinase co-activation for cancer therapy. Drug Discovery Today, 22(1), 72‑84.
https://doi.org/10.1016/j.drudis.2016.07.010
TONON, Giovanni. 2008. From oncogene to network addiction: the new frontier of cancer genomics and therapeutics. Future Oncology, 4(4), 569‑577.
https://doi.org/10.2217/14796694.4.4.569
TORTI, Davide, TRUSOLINO, Livio. 2011. Oncogene addiction as a foundational rationale for targeted anti-cancer therapy: promises and perils. EMBO Molecular Medicine, 3(11), 623‑636.
https://doi.org/10.1002/emmm.201100176
TURNER, Nicholas C., REIS-FILHO, Jorge S. 2012. Genetic heterogeneity and cancer drug resistance. The Lancet Oncology, 13(4), e178‑e185.
https://doi.org/10.1016/S1470-2045(11)70335-7
VOGT, Henrik, ULVESTAD, Elling, ERIKSEN, Thor Eirik, GETZ, Linn. 2014. Getting personal: can systems medicine integrate scientific and humanistic conceptions of the patient?: Systems medicine and the patient. Journal of Evaluation in Clinical Practice, 20(6), 942‑952.
https://doi.org/10.1111/jep.12251
WEINSTEIN, I. Bernard. 2002. CANCER: Enhanced: Addiction to Oncogenes-the Achilles Heal of Cancer. Science, 297(5578), 63‑64.
https://doi.org/10.1126/science.1073096
WEINSTEIN, I. Bernard, JOE, Andrew K. 2006. Mechanisms of Disease: oncogene addiction-a rationale for molecular targeting in cancer therapy. Nature Clinical Practice Oncology, 3(8), 448‑457.
https://doi.org/10.1038/ncponc0558
WEST, Lisandra, et al. 2012. A Novel Classification of Lung Cancer into Molecular Subtypes. PLoS ONE, 7(2).
https://doi.org/10.1371/journal.pone.0031906
WOLKENHAUER, Olaf, GREEN, Sara. 2013. The search for organizing principles as a cure against reductionism in systems medicine. The FEBS journal, 280 (23), 5938‑5948.
https://doi.org/10.1111/febs.12311
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2018-03-27
Comment citer
Darrason, Marie. 2018. « Médecine De précision Et médecine Des systèmes : La médecine personnalisée Se Trompe-T-Elle De Cible ? ». Lato Sensu: Revue De La Société De Philosophie Des Sciences 4 (2). https://doi.org/10.20416/lsrsps.v4i2.983.
Numéro
Rubrique
Les enjeux contemporains de la médecine personnalisée
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