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Perspectives: Bench to Bedside and Back

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Targeted Cancer Therapy

Part of the book series: Current Clinical Oncology™ ((CCO))

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Abstract

Translational medicine has opened the gateway to the era of personalized medicine. No longer a “one size fits all” approach, the treatment of cancer is now based on an understanding of underlying biologic mechanisms and is increasingly being tailored to the molecular specificity of a tumor. Although oncology still functions within broad disease categories, the future will see an increasing shift to treatment based on the characteristics of an individual’s tumor type. Interestingly, one of the first targeted therapies, all-trans retinoic acid in acute promyelocytic leukemia, was first demonstrated at the bedside with a subsequent return to the bench to elucidate its underlying basis. This was a translocation resulting in disruption of the retinoic acid receptor-α gene. Since then, a rigorous translational approach has led to other success stories, such as imatinib and dasatinib in Philadelphia-positive leukemias. With the discovery of novel biologic agents, future challenges lie in the investigation of optimal combinations and the identification of biomarkers that can provide both predictive and prognostic information. Genomics, proteomics, and the application of mathematical modeling are leading the way to biomarker discovery. Further elucidation of the cancer “stem cell hypothesis” will lead to treatment with combinations of agents used to target both early epigenetic mechanisms and downstream molecular events. With targeted agents that demonstrate increased efficacy and decreased toxicity, we are now approaching cancer as a chronic disease model. Personalized medicine, with a “bench to bedside and back” paradigm is poised to permanently alter the landscape for cancer management.

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References

  1. Goodman LS, Wintrobe MM, Dameshek W, et al. Nitrogen mustard therapy: use of methyl-bis(beta-chloroethyl)amine hydrochloride and tris(beta-chloroethyl)amine hydrochloride for Hodgkin’s disease, lymphosarcoma, leukemia, and certain allied and miscellaneous disorders. JAMA 1946;105:475–6. Reprinted in JAMA 1984;251:2255–61.

    Google Scholar 

  2. Hillestad LK. Acute promyelocytic leukemia. Acta Med Scand 1957;159:189–94.

    Article  PubMed  CAS  Google Scholar 

  3. Fenaux P, Chevret S, Guerci A, et al. Long-term follow-up confirms the benefit of all-trans retinoic acid in acute promyelocytic leukemia. Leukemia 2000;14:1371–7.

    Article  PubMed  CAS  Google Scholar 

  4. Tallman MS, Andersen JW, Schiffer CA, et al. All-trans-retinoic acid in acute promyelocytic leukemia. N Engl J Med 1997;337:1021–8.

    Article  PubMed  CAS  Google Scholar 

  5. Zhou GB, Zhao WL, Wang ZY, et al. Retinoic acid and arsenic for treating acute promyelocytic leukemia. PLoS Med 2005;2:e12.

    Article  PubMed  CAS  Google Scholar 

  6. Warrell RP Jr, de The H, Wang ZY, et al. Acute promyelocytic leukemia. N Engl J Med 1993;329:177–89.

    Article  PubMed  CAS  Google Scholar 

  7. Wang ZY. Ham-Wasserman lecture: treatment of acute leukemia by inducing differentiation and apoptosis hematology. Am Soc Hematol Educ Program 2003;1–13.

    Google Scholar 

  8. Weinstein, IB. Cancer: addiction to oncogenes—the Achilles heal of cancer. Science 2002;297:63–4.

    Article  PubMed  CAS  Google Scholar 

  9. Tsai S, Collins SJ. A dominant negative retinoic acid receptor blocks neutrophil differentiation at the promyelocyte stage. Proc Natl Acad Sci U S A 1993;90:7153–7.

    Article  PubMed  CAS  Google Scholar 

  10. Labrecque J, Allan D, Chambon P, et al. Impaired granulocytic differentiation in vitro in hematopoietic cells lacking retinoic acid receptors alpha1 and gamma. Blood 1998;92:607–15.

    PubMed  CAS  Google Scholar 

  11. Warrell RP Jr, Frankel SR, Miller WH, et al. Differentiation therapy of acute promyelocytic leukemia with tretinoin (all-trans-retinoic acid). N Engl J Med 1991;324:1385–93.

    Article  PubMed  Google Scholar 

  12. Avvisati G, Lo Coco F, Mandelli F. Acute promyelocytic leukemia: clinical and morphologic features and prognostic factors. Semin Hematol 2001;38:4–12.

    Article  PubMed  CAS  Google Scholar 

  13. Collins SJ. Acute promyelocytic leukemia: relieving repression induced remission. Blood 1998;91:2631–3.

    PubMed  CAS  Google Scholar 

  14. Nervi C, Ferrara FF, Fanelli M, et al. Caspases mediate retinoic acid-induced degradation of the acute promyelocytic leukemia PML/RARalpha fusion protein. Blood 1998;92:2244–51.

    PubMed  CAS  Google Scholar 

  15. Zhu J, Gianni M, Kopf E, et al. Retinoic acid induces proteasome-dependent degradation of retinoic acid receptor alpha (RARalpha) and oncogenic RARalpha fusion proteins. Proc Natl Acad Sci USA 1999;96:14807–12.

    Article  PubMed  CAS  Google Scholar 

  16. Zhu J, Shi XG, Chu HY, et al. Effect of retinoic acid isomers on proliferation, differentiation and PML relocalization in the APL cell line NB4. Leukemia 1995;9:302–9.

    PubMed  CAS  Google Scholar 

  17. Salomoni P, Pandolfi PP. The role of PML in tumor suppression. Cell 2002;108:165–70.

    Article  PubMed  CAS  Google Scholar 

  18. Shen ZX, Chen GQ, Ni JH, et al. Use of arsenic trioxide (As2O3) in the treatment of acute promyelocytic leukemia (APL). II. Clinical efficacy and pharmacokinetics in relapsed patients. Blood 1997;89:3354–60.

    PubMed  CAS  Google Scholar 

  19. Kurzrock R, Shtalrid M, Romero P, et al. A novel C-abl protein product in Philadelphia-positive acute lymphoblastic leukaemia. Nature 1987;325:631–5.

    Article  PubMed  CAS  Google Scholar 

  20. Tibes R, Trent J, Kurzrock R. Tyrosine kinase inhibitors and the dawn of molecular cancer therapeutics. Annu Rev Pharmacol Toxicol 2005;45:357–84.

    Article  PubMed  CAS  Google Scholar 

  21. Shepherd P, Suffolk R, Halsey J, et al. Analysis of molecular breakpoint and m-RNA transcripts in a prospective randomized trial of interferon in chronic myeloid leukaemia: no correlation with clinical features, cytogenetic response, duration of chronic phase, or survival. Br J Haematol 1995;89:546–54.

    PubMed  CAS  Google Scholar 

  22. Gorre M, Mohammed M, Ellwood K, et al. Clinical resistance to STI-571 cancer therapy caused by BCR-ABL gene mutation or amplification. Science 2001;293:876–80.

    Article  PubMed  CAS  Google Scholar 

  23. Shah NP, Nicoll JM, Nagar B, et al. Multiple BCR-ABL kinase domain mutations confer polyclonal resistance to the tyrosine kinase inhibitor imatinib (ST1571) in chronic phase and blast crisis chronic myeloid leukemia. Cancer Cell 2002;2:1117.

    Article  Google Scholar 

  24. Shah NP, Tran C, Lee FY, et al. Overriding imatinib resistance with a novel ABL kinase inhibitor. Science 2004;305:399–401.

    Article  PubMed  CAS  Google Scholar 

  25. Sawyers CL, Kantarjian H, Shah N, et al. Dasatinib (BMS-354825) in patients with chronic myeloid leukemia (CML) and Philadelphia-chromosome positive acute lymphoblastic leukemia (Ph+ ALL) who are resistant or intolerant to imatinib: update of a phase I study. Presented at the American Society of Hematology 47th Annual Meeting, 2005. Abstract 38.

    Google Scholar 

  26. Sawyers CL, Shah NP, Kantarjian HM, et al. Hematologic and cyogenetic responses in imatinib-resistant chronic phase chronic myeloid leukemia patients treated with the dual SRC/ABL kinase inhibitor BMS-354825: results from a phase I dose escalation study. Presented at the American Society of Hematology 46th Annual Meeting, 2005. Abstract 128.

    Google Scholar 

  27. Talpaz M, Shah NP, Kantarjian H, et al. Dasatinib in imatinib-resistant Philadelphia chromosome-positive leukemias. N Engl J Med 2006;35:2531–41.

    Article  Google Scholar 

  28. Kantarjian H, Pasquini R, Hamerschlak N, et al. Dasatinib or high-dose imatinib for chronic-phase chronic myeloid leukemia after failure of first-line imatinib: a randomized phase-2 trial. Blood 2007;109:5143–50.

    Article  PubMed  CAS  Google Scholar 

  29. Kurzrock R, Talpaz M, Li L, et al. Distinct biological impact of dephosphorylation vs downregulation of p210Bcr-Abl: implications for imatinib mesylate response and resistance. Leuk Lymphoma 2006;47:1651–64.

    Article  PubMed  CAS  Google Scholar 

  30. Abbott LH, Michor F, Mathematical models of targeted cancer therapy. Br J Cancer 2006;95:1136–41.

    Article  PubMed  CAS  Google Scholar 

  31. Charusanti P, Hu X, Chen L, et al. A mathematical model of BCR-ABL autophosphorylation signaling through the CRKL pathway, and Gleevec dynamics in chronic myeloid leukemia. Discrete Continuous Dynam Syst Ser B 2004;4:99–114.

    Google Scholar 

  32. Michor F, Hughes TP, Iwasa Y, et al. Dynamics of chronic myeloid leukemia. Nature 2005;435:1267–70.

    Article  PubMed  CAS  Google Scholar 

  33. Demetri GD, von Mehren M, Blanke CD, et al. Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. N Engl J Med 2002;347:472–80.

    Article  PubMed  CAS  Google Scholar 

  34. Dagher R, Cohen M, Williams G, et al. Approval summary: imatinib mesylate in the treatment of metastatic and/or unresectable malignant gastrointestinal stromal tumors. Clin Cancer Res 2002;8:3034–8.

    PubMed  CAS  Google Scholar 

  35. Verweij J, Casali P, Zalcberg J, et al. Progression-free survival in gastrointestinal stromal tumours with high-dose imatinib: randomised trial. Lancet 2004:364:1127–34.

    Article  PubMed  CAS  Google Scholar 

  36. Mazur MT, Clark HB. Gastric stromal tumors: reappraisal of histogenesis. Am J Surg Pathol 1983;7:507–19.

    PubMed  CAS  Google Scholar 

  37. Ng EH, Pollock RE, Munsell MF, et al. Prognostic factors influencing survival in gastrointestinal leiomyosarcomas: implications for surgical management and staging. Ann Surg 1992;215:68–77.

    Article  PubMed  CAS  Google Scholar 

  38. Pierie JP, Choudry U, Muzikansky A, et al. The effect of surgery and grade on outcome of gastrointestinal stromal tumors. Arch Surg 2001;136:383–9.

    Article  PubMed  CAS  Google Scholar 

  39. Plaat BE, Hollema H, Molenaar WM, et al. Soft tissue leiomyosarcomas and malignant gastrointestinal stromal tumors: differences in clinical outcome and expression of multidrug resistance proteins. J Clin Oncol 2000;18:3211–20.

    PubMed  CAS  Google Scholar 

  40. Ryan DP, Puchalski T, Supko JG, et al. A phase II and pharmacokinetic study of ecteinascidin 743 in patients with gastrointestinal stromal tumors. Oncologist 2002;7:531–8.

    Article  PubMed  CAS  Google Scholar 

  41. Edmonson JH, Marks RS, Buckner JC, et al. Contrast of response to dacarbazine, mitomycin, doxorubicin, and cisplatin (DMAP) plus GM-CSF between patients with advanced malignant gastrointestinal stromal tumors and patients with other advanced leiomyosarcomas. Cancer Invest 2002;20:605–12.

    Article  PubMed  CAS  Google Scholar 

  42. Trent JC, Beach J, Burgess MA, et al. A two-arm phase II study of temozolomide in patients with advanced gastrointestinal stromal tumors and other soft tissue sarcomas. Cancer 2003;98:2693–9.

    Article  PubMed  CAS  Google Scholar 

  43. De Pas T, Casali PG, Toma S, et al. Gastrointestinal stromal tumors: should they be treated with the same systemic chemotherapy as other soft tissue sarcomas? Oncology 2003;64:186–8.

    Article  PubMed  Google Scholar 

  44. Antman K, Crowley J, Balcerzak SP, et al. An intergroup phase III randomized study of doxorubicin and dacarbazine with or without ifosfamide and mesna in advanced soft tissue and bone sarcomas. J Clin Oncol 1993;11:1276–85

    PubMed  CAS  Google Scholar 

  45. Hirota S, Isozaki K, Moriyama Y, et al. Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors. Science 1998;279:577–80.

    Article  PubMed  CAS  Google Scholar 

  46. Tuveson DA, Willis NA, Jacks T, et al. STI571 inactivation of the gastrointestinal stromal tumor c-KIT oncoprotein: biological and clinical implications. Oncogene 2001;20:5054–8.

    Article  PubMed  CAS  Google Scholar 

  47. Joensuu H, Roberts PJ, Sarlomo-Rikala M, et al. Effect of the tyrosine kinase inhibitor ST1571 in a patient with a metastatic gastrointestinal stromal tumor. N Engl Med 2001;344:1052–6.

    Article  CAS  Google Scholar 

  48. Van Oosterom AT, Judson I, Verweij J, et al. Safety and efficacy of imatinib (STI571) in metastatic gastrointestinal stromal tumours: phase I study. Lancet 2001;358:1421–3.

    Article  PubMed  Google Scholar 

  49. Van Glabbeke M, Verweij J, Casali PG, et al. Initial and late resistance to imatinib in advanced gastrointestinal stromal tumors is predicted by different prognostic factors: a European Organisation for Research and Treatment of Cancer–Italian Sarcoma Group–Australasian Gastrointestinal Trials Group Study. J Clin Oncol 2005;23:5795–804.

    Article  PubMed  CAS  Google Scholar 

  50. Rankin C, Mehren MV, Blanke C. Dose effect of imatinib in patients with metastatic GIST: phase III sarcoma group study S0033. J Clin Oncol 2004;22(suppl):819s. Abstract 9005.

    Google Scholar 

  51. Verweij J, Casali P, Zalcberg J, et al. Progression-free survival in gastrointestinal stromal tumours with high-dose imatinib: randomised trial. Lancet 2004;364:1127–34.

    Article  PubMed  CAS  Google Scholar 

  52. Williams DE, Eisenman J, Baird A, et al. Identification of a ligand for the c-kit proto-oncogene. Cell 1990;63:167–74.

    Article  PubMed  CAS  Google Scholar 

  53. Sarlomo-Rikala M, Kovatich AJ, Barusevicius A, et al. CD117: a sensitive marker for gastrointestinal stromal tumors that is more specific than CD34. Mod Pathol 1998;11:728–34.

    PubMed  CAS  Google Scholar 

  54. Nakahara M, Isozaki K, Hirota S, et al. A novel gain-of-function mutation of c-kit gene in gastrointestinal stromal tumors. Gastroenterology 1998;115:1090–5.

    Article  PubMed  CAS  Google Scholar 

  55. Moskaluk CA, Tian Q, Marshall CR, et al. Mutations of c-kit JM domain are found in a minority of human gastrointestinal stromal tumors. Oncogene 1999;18:1897–902.

    Article  PubMed  CAS  Google Scholar 

  56. Hirota S, Nishida T, Isozaki K, et al. Gain-of-function mutation at the extracellular domain of KIT in gastrointestinal stromal tumors. J Pathol 2001;193:505–10.

    Article  PubMed  CAS  Google Scholar 

  57. Kim TW, Lee H, Kang YK, et al. Prognostic significance of c-kit mutation in localized gastrointestinal stromal tumors. Clin Cancer Res 2004;10:3076–81.

    Article  PubMed  CAS  Google Scholar 

  58. Singer S, Rubin BP, Lux ML, et al. Prognostic value of KIT mutation type, mitotic activity, and histologic subtype in gastrointestinal stromal tumors. J Clin Oncol 2002;20:3898–905.

    Article  PubMed  CAS  Google Scholar 

  59. Heinrich MC, Shoemaker JS, Corless CL, et al. Correlation of target kinase genotype with clinical activity of imatinib mesylate in patients with metastatic GI stromal tumors (GISTs) expressing KIT. Proc Am Soc Clin Oncol 2005;23:7. Abstract 7.

    Google Scholar 

  60. De Jong FA, Verweij J. Role of imatinib mesylate (Gleevec/Glivac) in gastrointestinal stromal tumors. Expert Rev Anticancer Ther 2003;3:757–66.

    Article  PubMed  Google Scholar 

  61. Weisberg E, Griffin JD. Resistance to imatinib (Glivec): update on clinical mechanisms. Drug Resist Update 2003;6:231–8.

    Article  CAS  Google Scholar 

  62. Miller KD, Burstein HJ, Elias AD, et al. Phase II study of SU11248, a multi-targeted receptor tyrosine kinase inhibitor (TKI), in patients with previously treated metastatic breast cancer (MBC). J Clin Oncol 2005;23:19s. Abstract 3001.

    Google Scholar 

  63. Chen H, Isozaki K, Kinoshita K, et al. Imatinib inhibits various types of activating mutant kit found in gastrointestinal stromal tumors. Int J Cancer 2003;105:130–5.

    Article  PubMed  CAS  Google Scholar 

  64. Goodman VL, Rock EP, Dagher R, et al. Approval summary: sunitinib for the treatment of imatinib refractory or intolerant gastrointestinal stromal tumors and advanced renal cell carcinoma. Clin Cancer Res 2007;13:1367–73.

    Article  PubMed  CAS  Google Scholar 

  65. Chen W, Cooper TK, Zahnow CA, et al. Epigenetic and genetic loss of Hic1 function accentuates the role of p53 in tumorigenesis. Cancer Cell 2004;6;387–98.

    Article  PubMed  Google Scholar 

  66. Esteller M. Epigenetics provides a new generation of oncogenes and tumour-suppressor genes. Br J Cancer 2006;94:179–83.

    Article  PubMed  CAS  Google Scholar 

  67. Pliml J, Sorm F. Synthesis of 2′-deoxy-d-ribofuranosyl-5-azacytosine. Coll Czech Chem Commun 1964;29:2576–7.

    CAS  Google Scholar 

  68. Fujita N, Takebayashi S, Okumura K, et al. Methylation-mediated transcriptional silencing in euchromatin by methyl-CpG binding protein MBD1 isoforms. Mol Cell Biol 1999;19z:6415–26.

    Google Scholar 

  69. Hendrich B, Abbott C, McQueen H, et al. Genomic structure and chromosomal mapping of the murine and human Mbd1, Mbd2, Mbd3, and Mbd4 genes. Mamm Genome 1999;10:906–12.

    Article  PubMed  CAS  Google Scholar 

  70. Kornblith AB, Herndon JE, Silverman LR, et al. Impact of azacytidine on the quality of life of patients with myelodysplastic syndrome treated in a randomized phase III trial: a Cancer and Leukemia Group B study. J Clin Oncol 2002;20:2441–52.

    Article  PubMed  CAS  Google Scholar 

  71. Silverman LR, Demakos EP, Peterson BL, et al. Randomized controlled trial of azacitidine in patients with the myelodysplastic syndrome: a study of the cancer and leukemia group B. J Clin Oncol 2002;20:2429–40.

    Article  PubMed  CAS  Google Scholar 

  72. Silverman LR, Holland JF, Weinberg RS, et al. Effects of treatment with 5-azacytidine on the in vivo and in vitro hematopoiesis in patients with myelodysplastic syndromes. Leukemia 1993;7:21–9.

    PubMed  Google Scholar 

  73. Aparicio A, Eads CA, Leong LA, et al. Phase I trial of continuous infusion 5-aza-2′-deoxycytidine. Cancer Chemother Pharmacol 2003;51:231–9.

    PubMed  CAS  Google Scholar 

  74. Sorm F, Vesely J. Effect of 5-aza-2′-deoxycytidine against leukemic and hemopoietic tissues in AKR mice. Neoplasma 1968;15:339–43.

    PubMed  CAS  Google Scholar 

  75. Wijermans P, Lübbert M, Verhoef G, et al. Low-dose 5-aza-2′-deoxycytidine, a DNA hypomethylating agent, for the treatment of high-risk myelodysplastic syndrome: a multicenter phase II study in elderly patients. J Clin Oncol 2000;18:956–62.

    PubMed  CAS  Google Scholar 

  76. Kantarjian H, Oki Y, Garcia-Manero G, et al. Results of a randomized study of 3 schedules of low-dose decitabine in higher-risk myelodysplastic syndrome and chronic myelomonocytic leukemia. Blood 2007;109:52–7.

    Article  PubMed  CAS  Google Scholar 

  77. Kantarjian H, Issa JP, Rosenfeld CS, et al. Decitabine improves patient outcomes in myelodysplastic syndromes: results of a phase III randomized study. Cancer 2006;106:1794–803.

    Article  PubMed  CAS  Google Scholar 

  78. Kantarjian HM, O’Brien S, Cortes J, et al. Results of decitabine (5-aza-2′ deoxycytidine) therapy in 130 patients with chronic myelogenous leukemia. Cancer 2003;98:522–8.

    Article  PubMed  CAS  Google Scholar 

  79. Issa JP. Decitabine. Curr Opin Oncol 2003;15:446–51.

    Article  PubMed  CAS  Google Scholar 

  80. Driscoll JS, Marquez VE, Plowman J, et al. Antitumor properties of 2(1H)-pyrimidinone riboside (zebularine) and its fluorinated analogues. J Med Chem 1991;34,3280–4.

    Article  PubMed  CAS  Google Scholar 

  81. Issa JP, Garcia-Manero G, Giles FJ, et al. Phase 1 study of low-dose prolonged exposure schedules of the hypomethylating agent 5-aza-2’-deoxycytidine (decitabine) in hematopoietic malignancies. Blood 2004;103:1635–40.

    Article  PubMed  CAS  Google Scholar 

  82. Issa JP, Gharibyan V, Cortes J, et al. Phase II study of low-dose decitabine in patients with chronic myelogenous leukemia resistant to imatinib mesylate. J Clin Oncol 2005;23:3948–56.

    Article  PubMed  CAS  Google Scholar 

  83. Lubbert M, Daskalakis M, Kunzmann R, et al. Nonclonal neutrophil responses after successful treatment of myelodysplasia with low-dose 5-aza-2′-deoxycytidine (decitabine). Leuk Res 2004;28:1267–71.

    Article  PubMed  CAS  Google Scholar 

  84. Aparicio A, Weber JS. Review of the clinical experience with 5-azacytidine and 5-aza-2’-deoxycytidine in solid tumors. Curr Opin Invest Drugs 2002;3:627–33.

    CAS  Google Scholar 

  85. Weiser T, Guo ZS, Ohnmacht GA, et al. Sequential 5-aza-2’-deoxycytidine-depsipeptide FR901228 treatment induces apoptosis preferentially in cancer cells and facilitates their recognition by cytolytic T lymphocytes specific for NY-ESO-1. J Immunother 2001;24:151–61.

    Article  CAS  PubMed  Google Scholar 

  86. Schrump DS, Fischette MR, Nguyen DM, et al. Phase I study of decitabine-mediated gene expression in patients with cancers involving the lungs, esophagus, or pleura. Clin Cancer Res 2006;12:5777–85.

    Article  PubMed  CAS  Google Scholar 

  87. Cameron EE, Bachman KE, Myöhönen S, et al. Synergy of demethylation and histone deacetylase inhibition in the re-expression of genes silenced in cancer. Nat Genet 1999;21:103–7.

    Article  PubMed  CAS  Google Scholar 

  88. Gore SD, Baylin S, Sugar E, et al. Combined DNA methyltransferase and histone deacetylase inhibition in the treatment of myeloid neoplasms. Cancer Res 2006;66:6361–9.

    Article  PubMed  CAS  Google Scholar 

  89. Garcia-Manero G, Kantarjian HM, Sanchez-Gonzalez B, et al. Phase 1/2 study of the combination of 5-aza-2′-deoxycytidine with valproic acid in patients with leukemia. Blood 2006;108:3271–9.

    Article  PubMed  CAS  Google Scholar 

  90. Rudek MA, Zhao M, He P, et al. Pharmacokinetics of 5-azacitidine administered with phenylbutyrate in patients with refractory solid tumors or hematologic malignancies. J Clin Oncol 2005;23:3906–11.

    Article  PubMed  CAS  Google Scholar 

  91. Jordan CT. Cancer stem cell biology: from leukemia to solid tumors. Curr Opin Cell Biol 2004;16:708–12.

    Article  PubMed  CAS  Google Scholar 

  92. Bedi A, Zehnbauer BA, Collector MI, et al. BCR-ABL gene rearrangement and expression of primitive hematopoietic progenitors in chronic myeloid leukemia. Blood 1993;81:2898–902.

    PubMed  CAS  Google Scholar 

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Authors
  1. Jennifer Wheler MD
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  2. Razelle Kurzrock MD, FACP
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Editors and Affiliations

  1. Department of Investigational Cancer Therapeutics Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX

    Razelle Kurzrock MD

  2. Department of Clinical Research, The University of Texas MD Anderson Cancer Center, Houston, TX

    Maurie Markman

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© 2008 Humana Press, Totowa, NJ

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Wheler, J., Kurzrock, R. (2008). Perspectives: Bench to Bedside and Back. In: Kurzrock, R., Markman, M. (eds) Targeted Cancer Therapy. Current Clinical Oncology™. Humana Press. https://doi.org/10.1007/978-1-60327-424-1_1

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  • DOI: https://doi.org/10.1007/978-1-60327-424-1_1

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