Cancer is one of the leading causes of death in the United States, and more than 1.5 million new cases and more than 0.5 million deaths were reported during 2010 in the United States alone. Following completion of the sequencing of the human genome, substantial progress has been made in characterizing the human epigenome, proteome, and metabolome; a better understanding of pharmacogenomics has been developed, and the potential for customizing health care for the individual has grown tremendously. Recently, personalized medicine has mainly involved the systematic use of genetic or other information about an individual patient to select or optimize that patient’s preventative and therapeutic care. Molecular profiling in healthy and cancer patient samples may allow for a greater degree of personalized medicine than is currently available. Information about a patient’s proteinaceous, genetic, and metabolic profile could be used to tailor medical care to that individual’s needs. A key attribute of this medical model is the development of companion diagnostics, whereby molecular assays that measure levels of proteins, genes, or specific mutations are used to provide a specific therapy for an individual’s condition by stratifying disease status, selecting the proper medication, and tailoring dosages to that patient’s specific needs. Additionally, such methods can be used to assess a patient’s risk factors for a number of conditions and to tailor individual preventative treatments. Recent advances, challenges, and future perspectives of personalized medicine in cancer are discussed.
References
[1]
Siewert, S.Y.; Catenacci, D.V.; Stricker, T. Molecular profiling of cancer—the future of personalized cancer medicine: a primer on cancer biology and the tools necessary to bring molecular testing to the clinic. Semin. Oncol. 2011, 38, 173–185, doi:10.1053/j.seminoncol.2011.01.013. 21421108
[2]
Safgren, S.L.; Kuffel, M.J.; Ulmer, H.U.; Bol？nder, J.; Strick, R.; Beckmann, M.W.; Koelbl, H; Weinshilboum, R.M.; Ingle, J.N.; Eichelbaum, M.; Schwab, M.; Brauch, H.; Ames, M.M.; Suman, V.J.; Simon, W.; Fritz, P.; Winter, S.; Schmidt, M.; Fasching, P.A.; Hamann, U.; Goetz, M.P.; Schroth, W. Association between CYP2D6 polymorphisms and outcomes among women with early stage breast cancer treated with tamoxifen. JAMA 2009, (302), 1429–1436.
[3]
Offit, K. Personalized medicine: new genomics, old lessons. Hum. Genet. 2011, 130, 3–14, doi:10.1007/s00439-011-1028-3. 21706342
[4]
Barrett, M.T.; Kiefer, J.A.; Bussey, K.J.; Demeure, M.J.; Lee, M.; Baehner, F.L. Genomic signatures of cancer: basis for individualized risk assessment, selective staging and therapy. J. Surg. Oncol. 2011, 103, 563–573, doi:10.1002/jso.21838. 21480251
[5]
Kang, D.; Lee, K.M.; Song, M. Breast cancer prevention based on gene-environment interaction. Mol. Carcinog. 2011, 50, 280–290, doi:10.1002/mc.20639. 21465576
[6]
Olopade, O.I.; de Souza, J.A. CYP2D6 genotyping and tamoxifen: an unfinished story in the quest for personalized medicine.. Semin. Oncol. 2011, 38, 263–273, doi:10.1053/j.seminoncol.2011.01.002. 21421116
[7]
Schwab, B.; Eichelbaum, M.; Murdter, T.E.; Brauch, H. Pharmacogenomics of tamoxifen therapy. Clin. Chem. 2009, 55, 1770–1782, doi:10.1373/clinchem.2008.121756. 19574470
[8]
Jordan, V.C.; Brauch, H. Targeting of tamoxifen antitumor action for the treatment and prevention of breast cancer: the “personalized approach.”. Eur. J. Cancer. 2009, (45), 2274–2283.
[9]
McLeod, H.L.; Carey, L.A.; Hoskins, J.M. CYP2D6 and tamoxifen: DNA matters in breast cancer. Nat. Rev. Cancer 2009, 9, 576–586, doi:10.1038/nrc2683. 19629072
[10]
Brauch, H.; Schwab, M.; Eichelbaum, M.; Winter, S.; Dauser, S.; Fasching, A.P.; Hammen, U.; Schroth, W. CYP2D6 polymorphism as predictors of outcome in breast cancer patients treated with tamoxifen: expanded polymorphism coverage improves risk stratification. Clin. Cancer Res. 2010, 16, 4468–4477, doi:10.1158/1078-0432.CCR-10-0478. 20515869
[11]
Wang, H.; Souchon, E.; Holmes, F.; Vidaurre, T.; Lluch, A.; Esserman, L.; Booser, D.J.; Valero, V.; Pusztai, L.; Hatzis, C. A genomic predictor of response and survival following taxane-anthracyclin chemotherapy for invasive breast cancer. JAMA 2011, (305), 1873–1881.
[12]
Nishio, K.; Maegawa, M.; Matsumoto, K.; Arao, T. What can and cannot be done using a microarray analysis? Traetment stratification and clinical applications in oncology. Biol. Pharm. Bull. 2011, 34, 1789–1793, doi:10.1248/bpb.34.1789. 22130232
Desnick, R.J.; Raptis, G.; Kemeny, M.; Kasai, Y.; Yu, C.; Peter, I.; Jaremko, M.; Barginear, M.F. Increasing tamoxifen dose in breast cancer patients based on CYP2D6 genotypes and endoxifen levels: effect of and active metabolite isomers and the antiestrogenic activity score. Clin. Pharmacol. Ther. 2011, 90, 605–611, doi:10.1038/clpt.2011.153. 21900890
[15]
Lash, T.L.; Conin-Fenton, D.P. Clinical epidemiology and pharmacology of CYp2D6 inhibition related to breast cancer outcomes. Expert Rev. Clin. Pharmacol. 2011, 4, 363–377, doi:10.1586/ecp.11.18. 21709817
[16]
Walley, T.; Oyee, J.; Newman, W.; Howell, S.; Fernández Santander, A.; Dundar, Y.; Dickson, R.; Boland, A.; Payne, K.; Martin, S.C.; Fleeman, N. The clinical effectiveness and cost-effectiveness of genotyping for CYP2D6 for the management of women with breast cancer with tamoxifen: a systematic review. Health Technol. Assess. 2011, 15, 1–102. 21609648
[17]
Flockhart, D.A.; Cushman, M.; Mayhoub, A.S.; Pei, Z.; Xu, C.; Lu, W.J. The temoxifen metabolite norendoxifen is a potent and selective inhibitor of aromatase (CYP19) and a potential lead compound for novel therapeutic agents. Breast Cancer Res. Treat. 2011, 363–377.
[18]
Zwart, W.; Ropeman, P.; Krigsman, O. A diagnostic gene profile for molecular subtyping of breat cancer associated with treatment response. Breast Cancer Res. Treat. 2011, 363–377. 21814749
[19]
Werutsky, G.; Cardoso, F.; Ravdin, P.M.; Pierga, J.Y.; Vindevoghel, A.; Nitz, U.; Passalacqua, R.; Thompson, A.M.; Viale, G.; Rubio, I.T.; Veer, L.V.; Delaloge, S.; Bogaerts, J.; Pictaart-Gebhart, M.J.; Rutgers, E. The EORTC 10041/BIG 03–04 MINDACT trial is feasible: results of the pilot phase. Eur. J. Cancer 2011, (47), 2742–2749.
[20]
Fumagalli, D.; Bohn, O.L.; Shak, S.; Watson, D.; Cronin, M.T.; Baker, J.; Baehner, F.L.; Costantino, J.P.; Pogue-Geile, K.L.; Tang, G.; Kim, C.; et al. Estrogen receptor (ESR1) mRNA expression and benefit from tamoxifen in the treatment and prevention of estrogen-receptor-positive breast cancer. J. Clin. Oncol. 2011, 29, 4160–4167, doi:10.1200/JCO.2010.32.9615. 21947828
[21]
Polite, B.; Kindler, H.L.; Kozloff, M.; Catenacci, D.V. Personalized colon cancer care in 2010. Semin. Oncol. 2011, 38, 284–308, doi:10.1053/j.seminoncol.2011.01.001. 21421118
[22]
Venook, A.P.; Phillips, K.A.; Van Bebber, S.L.; Kelley, R.K. Personalized medicine and oncology practice guidelines: a case study of contemporary biomarkers in colorectal cancer. J. Natl. Compr. Canc. Netw. 2011, 9, 13–25. 21233242
[23]
Chang, D.D.; Patterson, S.D.; Radinsky, R.; Suggs, S.; Sikorski, R.; Juan, T.; Freeman, D.J.; Siena, S.; van Cutsem, E.; Peeters, M.; Wolf, M.; Amado, R.G. Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer. J. Clin. Oncol. 2008, 26, 1626–1634, doi:10.1200/JCO.2007.14.7116. 18316791
[24]
Eckhardt, S.G.; Franklin, W.A.; Hirsch, F.R.; Messersmith, W.A.; Jimeno, A. ？KRS mutations and sensitivity to epidermal growth factor receptor inhibitors in colorectal cancer: practical application of patient selection. J. Clin. Oncol. 2009, 27, 1130–1136, doi:10.1200/JCO.2008.19.8168. 19124802
[25]
André, T.; Louvet, C.; Landi, B.; Bouché, O.; Ychou, M.; Buc, E.; Le Corre, D.; Cayre, A.; Boige, V.; Bachet, J.B.; Lievre, A.; et al. KRAS mutations as an independent prognostic factor in patients with advanced colorectal cancer treated with cetuximab. J. Clin. Oncol. 2008, 26, 374–379, doi:10.1200/JCO.2007.12.5906. 18202412
[26]
van den Brule, A.J.; Rutten, H.J.; Lemmens, V.E.; Lijnshoten, G.; Sarasqueta, F. Pharmacogenetics of oxaliplatin as adjuvant treatment in colon carcinoma: are single nucleotide polymorphisms in GSTP1, ERCC1, and ERCC2 good predictive markers? Diagn. Ther. 2011, 15, 277–283.
[27]
Herrera, L.A.; Arrieta, O.; Serrano, A.; Herrera, R.; Castro, C.; Calderillo, G.; Bauza, A.; Santibanez, M.; Castillo-Fernandez, O. Methylenetetrahydrofolatereductase polymorphism (677 C-T) predicts long time to progression in metastatic colon cancer treated with 5-fluorouracil and folinic acid. Arch. Med. Res. 2010, 41, 430–433, doi:10.1016/j.arcmed.2010.08.011. 21044746
[28]
Aranda, E.; Garcia-Foncillas, J.; Maiello, E.; Gomez, M.A.; Bandrés, E.; Villa, J.C.; Zarate, R.; Boni, V. Role of primary miRNA polymorphic variants in metastatic colon cancer patients treated with 5-fluorouracil and irinotecan. Pharmacogenomics 2011, 11, 429–436, doi:10.1038/tpj.2010.58.
[29]
Hensing, T.; Campbell, N.; Salama, A.K.; Maitland, M.; Hoffman, P.; Villaflor, V.; Vokes, E.E.; Salgia, R. Personalized treatment of lung cancer. Semin. Oncol. 2011, 38, 74–83.
[30]
Curran, M.P. Crizotinib: in locally advanced or metastatic non-small cell lung cancer. Drugs 2012, 72, 99–107, doi:10.2165/11207680-000000000-00000. 22191798
[31]
Ou, S.H. Crizotinib: a novel and first-in-class multitargeting tyrosine kinase inhibitor for the treatment of anaplastic lymphoma kinase rearranged non-small cell lung cancer and beyond. Drug Des. Devel. Ther. 2011, 5, 471–485. 22162641
[32]
Kenudson, M.M.; Solomon, B.; Shaw, A.T. Crizotinib and testing for ALK. J. Natl. Compr. Netw. 2011, 9, 1335–1345.
[33]
Pao, W.; Rizvi, N.; Miller, V.; Stout, T.; Kris, M.G.; Viale, A.; Hutchinson, K.; Chen, X.; Zhao, Z.; Shen, R.; Aftab, D.; Pietanza, M.C.; Chmielecki, J. EGRR-mutant lung adenocarcinomas treated first line with the novel EGFR inhibitor, XL647, can subsequently retain moderate sensitivity to erlotinib. J. Thorac. Oncol. 2011, 1335–1345. 22173702
[34]
von Pawel, J.; Pereira, J.R.; Paz-Ares, L.; Kortsik, C.; Hotko, Y.; Martens, U.M.; Eschbach, C.; Barrios, C.; Bondarenko, I.; Gatzemeir, U.; O’Byrne, K.J.; et al. Molecular biomarkers in non-small cell lung cancer: a retrospective analysis of data from the phase III FLEX study. Lancet Oncol. 2011, 12, 795–805, doi:10.1016/S1470-2045(11)70189-9. 21782507
[35]
Kato, H.; Ohe, Y.; Nakata, K.; Fukuoka, M.; Umemura, T.; Hada, S.; Jawaid, A.; Takahashi, A.; Mushiroda, T.; Barratt, B.J.; Nyberg, F.; et al. Interstitial lung disease in gefitinib treated Japanese patients with non-small cell lung cancer: genome-wide analysis of genetic data. Pharmacogenomics 2011, 12, 965–977, doi:10.2217/pgs.11.38. 21787189
[36]
Liu, Z.Q.; Zhou, H.H.; Xu, X.J.; Huang, Q.; Han, L.F.; Yin, J.Y. ABCC1 polymorphism Arg723Gln (2168G – A) is associated with lung cancer susceptibility in a Chinese population. Clin. Exp. Pharmaco. Physiol. 2011, 38, 632–637, doi:10.1111/j.1440-1681.2011.05571.x.
[37]
Yang, P.C.; Yu, C.J.; Yang, C.H.; Chen, K.Y.; Shih, J.Y.; Wu, J.Y. Gefitinib therapy in patients with advanced non-small cell lung cancer with or without testing for epidermal growth factor receptor (EGFR) mutations. Medicine 2011, 90, 159–167, doi:10.1097/MD.0b013e31821a16f4. 21512416
[38]
Osawa, K. SNPs in ERCC1 and drug response to cisplatin in non-small cell lung cancer patients. Pharmacogenomics 2011, 12, 445–447, doi:10.2217/pgs.11.15. 21521014
[39]
Dale, W.; Posadas, E.; Szmulewitz, R.; Mohile, S.G.; Sajid, S. Individualized decision-making for older men with prostate cancer: balancing cancer control with treatment consequences across the clinical spectrum. Semin. Oncol. 2011, 38, 309–325, doi:10.1053/j.seminoncol.2011.01.011. 21421119
Siffert, W.; Schmid, K.W.; Rübben, H.; Eisenhardt, A.; Nückel, H.; Buettner, R.; Kahl, P.; Hilburn, C.F.; Schmitz, K.J.; Heukamp, L.C.; Bachmann, H.S.; et al. Regulatory BCL2 promoter polymorphism (938 C–A) is associated with adverse outcome in patients with prostate carcinoma. Int. J. Cancer. 2011, 129, 2390–2399, doi:10.1002/ijc.25904. 21207420
[42]
Stock, W.; Larson, R.A.; Godley, L.A.; Artz, A.S.; Thirman, M.J.; Odenike, O. Gene mutations, epigenetic dysregulation, and personalized therapy in myeloid neoplasia; are we there yet? Semin. Oncol. 2011, 38, 196–214, doi:10.1053/j.seminoncol.2011.01.010. 21421110
[43]
Onel, K.; Lussier, Y.; Leong, H.; Larson, R.A.; McNerney, M.E.; Gurbuxani, S.; Huang, R.S.; Dolan, M.E.; Cunningham, J.; Godley, L.A.; et al. An integrated genomic approach to the assessment and treatment of acute myeloid leukemia. Semin. Oncol. 2011, 38, 215–224, doi:10.1053/j.seminoncol.2011.01.003. 21421111
[44]
Sawada, K.; Hirokawa, M.; Yoshioka, T.; Fujishima, N.; Saitoh, H.; Tagawa, H.; Kameoka, Y.; Kagaya, H.; Scott, S.A.; Miura, M.; Takahashi, N. Influence of CYP3A5 and drug transporter polymorphisms on imatinib trough concentration and clinical response among patients with chronic phase chronic myeloid leukemia. J. Hum. Genet. 2010, 55, 731–737, doi:10.1038/jhg.2010.98. 20720558
[45]
Smith, S.M.; van Besien, K.; Ramsdale, E. Personalized treatment of lymphoma: promise and reality. Semin Oncol. 2011, 38, 225–235, doi:10.1053/j.seminoncol.2011.01.008. 21421112
[46]
Gourmel, B.; Lallemand-Breitenbach, V.; Robledo-Sarmiento, M.; Rousselot, P.; Berthier, C.; Peres, L.; Soilihi, H.; Ferhi, O.; Guillemin, M.C.; Nasr, R.; et al. Eradication of acute promyelocytic leukemia-initiating cells through PML-RARA degradation. Nat. Med. 2008, 14, 1333–1342, doi:10.1038/nm.1891. 19029980
[47]
Simonsson, B.; Hoglund, M.; Barbany, G. Swedish CML Group. Complete molecular remission in chronic myelogenous leukemia after imatinib therapy. N. Eng. J. Med. 2002, 347, 539–540, doi:10.1056/NEJM200208153470719.
[48]
De Paoli, L.; Fangazio, M.; Franceschetti, S.; Bruscaggin, A.; Gloghini, A.; Forconi, F.; Fabbri, A.; Di Rocco, A.; Rasi, S.; Rossi, D.; et al. The host genetic background of DNA repair mechanisms is an independent predictor of survival in diffuse large B-cell lymphoma. Blood 2011, 117, 2405–2413, doi:10.1182/blood-2010-07-296244. 21156845
[49]
Gervasini, G.; de Murillo, S.G.; Casado, M.S.; Jimenez, M.; Caceres-Marzal, C.; Vagace, J.M. Methotrexate-induced subacute neurotoxicity in a child with acute lymphoblastic leukemia carrying genetic polymorphisms related to folate homeostasis. Am. J. Hematol. 2011, 86, 98–101, doi:10.1002/ajh.21897. 21064136
[50]
Sawyers, C.L.; Solit, D. Drug discovery: how melanomas bypass new Drug discovery: how melanomas bypass new therapy.therapy. Nature 2010, 468, 902–903, doi:10.1038/468902a. 21164474
