Personalized medicine in hematology - A landmark from bench to bed

Computational and Structural Biotechnology Journal

Volumn 10, Issue 17, 2014, Pages 70-77

  Badalian Very, Gayane ^a  

^a HARVARD MEDICAL SCHOOL   (United States)

Author keywords

Drug delivery; Hematology; Personalized medicine; Targeted therapies

Indexed keywords

DRUG DELIVERY SYSTEM; GENE EXPRESSION PROFILING; GENE SEQUENCE; HEMATOLOGY; HUMAN; PERSONALIZED MEDICINE; PHARMACOGENOMICS; POLYMERASE CHAIN REACTION; PRIORITY JOURNAL; REVIEW; TREATMENT RESPONSE;

EID: 84926290243     PISSN: None     EISSN: 20010370     Source Type: Journal    
DOI: 10.1016/j.csbj.2014.08.002     Document Type: Review

References (132)

1. Lawrence MS, Stojanov P, et al. Discovery and saturation analysis of cancer genes across 21 tumour types. Nature Jan 5 2014. http://dx.doi.org/10.1038/nature12912.
2. Alexandrov LB, Nik-Zainal S, et al. Signatures of mutational processes in human cancer. Nature Aug 22 2013; 500 (7463):415-21. http://dx.doi.org/10.1038/nature12477.
3. Badalian-Very G, Vergilio JA, et al. Recurrent BRAF mutations in Langerhans cell histiocytosis. Blood Sep 16 2010; 116 (11):1919-23. http://dx.doi.org/10.1182/blood-2010-04-279083.
4. Ylipää A, Yli-Harja O, Zhang W, Nykter M. Characterization of aberrant pathways across human cancers. BMC Syst Biol 2013; 7 (Suppl. 1):S1. http://dx.doi.org/10.1186/1752-0509-7-S1-S1.
5. Paul I, Bhattacharya S. Current understandingon EGFR and Wnt/β-catenin signaling in glioma and their possible crosstalk. Genes Cancer Nov 2013; 4 (11-12):427-46.
6. Koul HK, Pal M, Koul S. Role of p38 MAP kinase signal transduction in solid tumors. Genes Cancer Sep 2013; 4 (9-10):342-59.
7. Gäbler K, Behrmann I, et al. JAK2 mutants (e.g., JAK2V617F) and their importance as drug targets in myeloproliferative neoplasms. JAKSTAT Jul 1 2013; 2 (3):e25025.
8. Chmielecki J, Meyerson M. DNA sequencing of cancer: what have we learned? Annu Rev Med Nov 20 2013; 65:63-79. http://dx.doi.org/10.1146/annurev-med-060712-200152.
9. Leggett RM, Ramirez-Gonzalez RH, Ramirez-Gonzalez RH, Clavijo BJ, Waite D, Davey RP. Sequencing quality assessment tools to enable data-driven informatics for high throughput genomics. Front Genet Dec 17 2013; 4:288.
10. Hou L, Zhao H. A review of post-GWAS prioritization approaches. Front Genet Dec 9 2013; 4:280.
11. Borha A. Emerging paradigms in genomics-based crop improvements. Sci World J Nov 17 2013; 2013:585467.
12. Carter SL, Cibulskis K, et al. Absolute quantification of somatic DNA alterations in human cancer. Nat Biotechnol May 2012; 30 (5):413-21. http://dx.doi.org/10.1038/nbt.2203.
13. MacConaill LE, Van Hummelen P, Meyerson M, Hahn WC. Clinical implementation of comprehensive strategies to characterize cancer genome: opportunities and challenges. Cancer Discov Sep 2011; 1 (4):297-311. http://dx.doi.org/10.1158/2159-8290.CD-11-0110.
14. Wagle N, Berger MF, Davis M.J., et al. High-throughput detection of actionable genomic alterations in clinical tumor samples by targeted, massively parallel sequencing. Cancer Discov Jan 2012; 2 (1):82-93. http://dx.doi.org/10.1158/2159-8290.CD-11-0184.
15. Ding L, Getz G, et al. Somatic mutations affect key pathways in lung adenocarcino-ma. Nature Oct 23 2008; 455 (7216):1069-75. http://dx.doi.org/10.1038/nature07423.
16. Tournier C. The 2 faces of JNK signaling in cancer. Genes Cancer Sep 2013; 4 (9-10): 397-400.
17. Ebelt ND, Cantrell MA, et al. c-Jun N-terminal kinases mediate a wide range of targets in the metastatic cascade. Genes Cancer Sep 2013; 4 (9-10):378-87.
18. Jang YN, Baik EJ. JAK-STAT pathway and myogenic differentiation. JAKSTAT Apr 1 2013; 2 (2):e23282.
19. Francipane MG, Lagasse E. mTOR pathway in colorectal cancer: an update. Oncotarget Jan 15 2014; 5 (1):49-66.
20. Haroche J, Cohen-Aubart F, Van Den Berg CL. Dramatic efficacy of vemurafenib in both multisystemic and refractory Erdheim-Chester disease and Langerhans cell histiocytosis harboring the BRAF V600E mutation. Blood Feb 28 2013; 121 (9): 1495-500. http://dx.doi.org/10.1182/blood-2012-07-446286 [Epub 2012 Dec 20].
21. Arora A, Sholar EM. Role of tyrosine kinase inhibitors incancer therapy. J Pharmacol Exp Ther Dec 2005; 315 (3):971-9 (Epub 2005 Jul 7).
22. Hartmann JT, Haap M, et al. Tyrosine kinase inhibitors - a review on pharmacology, metabolism and side effects. Curr Drug Metab Jun 2009; 10 (5):470-81.
23. Druker BJ, Sawyers CL, et al. Activity of a specific inhibitor of the BCR-ABL tyrosine kinase in the blast crisis of chronic myeloid leukemia and acute lymphoblastic leukemia with the Philadelphia chromosome. N Engl J Med Apr 5 2001; 344 (14): 1038-42.
24. Force T, Krause DS, et al. Molecular mechanisms of cardiotoxicity of tyrosine kinase inhibition. Nat Rev Cancer May 2007; 7 (5):332-44.
25. Wang L, McLeod HL, Weinshilboum RM. Genomics and drug response. N Engl J Med Mar 24 2011; 364 (12):1144-53. http://dx.doi.org/10.1056/NEJMra1010600.
26. Hudson KL. Genomics, health care, and society. N Engl J Med Sep 15 2011; 365 (11): 1033-41. http://dx.doi.org/10.1056/NEJMra1010517.
27. Simon R. Drug-diagnostics co-development in oncology. Front Oncol Dec 23 2013; 3:315.
28. Utsugi T. New challenges and inspired answers for anticancer drug discovery and development. Jpn J Clin Oncol Oct 2013; 43 (10):945-53. http://dx.doi.org/10.1093/jjco/hyt131 [Epub 2013 Sep 5].
29. Montagna RA. Meeting the technical challenges of personalized medicine and companion diagnostics. MLO Med Lab Obs Jan 2012; 44 (1):16 [18, 20 passim].
30. Sweet K, Zhang L, Pinilla-Ibarz J. Biomarkers for determining the prognosis in chronic myelogenous leukemia. J Hematol Oncol Jul 19 2013; 6 (1):54.
31. Ashariati A, Ugroseno S. Profile of BCR-ABL transcript levels based on Sokal prognostic score in chronic myeloid leukemia patients treated with imatinib. Acta Med Indones Apr 2013; 45 (2):107-13.
32. Martin H, Mali RS. Pak and Rac GTPases promote oncogenic KIT-induced neoplasms. J Clin Invest Oct 1 2013; 123 (10):4449-63. http://dx.doi.org/10.1172/JCI67509 [Epub 2013 Sep 16].
33. Berger F, Reiser MF. Micro-RNAs as potential new molecular biomarkers in oncology: have they reached relevance for the clinical imaging sciences? Theranostics Nov 30 2013; 3 (12):943-52.
34. Stenvang J, Kümler I, et al. Biomarker-guided repurposing of chemotherapeutic drugs for cancer therapy: a novel strategy in drug development. Front Oncol Dec 25 2013; 3:313.
35. Goldberg MS, Hook SS, et al. Biotargeted nanomedicines for cancer: six tenets before you begin. Nanomedicine (Lond) Feb 2013; 8 (2):299-308. http://dx.doi.org/10.2217/nnm.13.3.
36. Kraft JC, Freeling JP, Wang Z, Ho RJ. Emerging research and clinical development trends of liposome and lipid nanoparticle drug delivery systems. J Pharm Sci Jan 2014; 103 (1):29-52. http://dx.doi.org/10.1002/jps.23773.
37. Goldberg MS. siRNA delivery for the treatment of ovarian cancer. Methods Sep 15 2013; 63 (2):95-100. http://dx.doi.org/10.1016/j.ymeth.2013.01.007 [Epub 2013 Feb 10].
38. Lee SG, Jeong JH, et al. Nanostructured lipid carrier-loaded hyaluronic acid microneedles for controlled dermal delivery of a lipophilic molecule. Int J Nanomedicine 2014; 9:289-99. http://dx.doi.org/10.2147/IJN.S54529.
39. MacConaill LE, Campbell CD, et al. Profiling critical cancer gene mutations in clinical tumor samples. PLoS One Nov 18 2009; 4 (11):e7887. http://dx.doi.org/10.1371/journal.pone.0007887.
40. Matulonis UA, Hirsch M, et al. High throughput interrogation of somatic mutations in high grade serous cancer of the ovary. PLoS One 2011; 6 (9):e24433. http://dx.doi.org/10.1371/journal.pone.0024433.
41. Ojesina AI, Lichtenstein L, et al. Landscape of genomic alterations in cervical carcinomas. Nature Dec 25 2013. http://dx.doi.org/10.1038/nature12881.
42. Sanger F. The early days of DNA sequences. Nat Med Mar 2001; 7 (3):267-8.
43. Sanger F, Nicklen S. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A Dec 1977; 74 (12):5463-7.
44. Sanger F, Coulson AR, et al. Cloning in single-stranded bacteriophage as an aid to rapid DNA sequencing. J Mol Biol Oct 25 1980; 143 (2):161-78.
45. MacConaill LE. Existing and emerging technologies for tumor genomic profiling. J Clin Oncol May 20 2013; 31 (15):1815-24. http://dx.doi.org/10.1200/JCO.2012.46.5948 [Epub 2013 Apr 15].
46. Verma M, Khoury MJ, Ioannidis JP. Opportunities and challenges for selected emerging technologies in cancer epidemiology: mitochondrial, epigenomic, metabolomic, and telomerase profiling. Cancer Epidemiol Biomarkers Prev Feb 2013; 22 (2):189-200. http://dx.doi.org/10.1158/1055-9965.EPI-12-1263.
47. Enkemann SA. Standards affecting the consistency of gene expression arrays in clinical applications. Cancer Epidemiol Biomarkers Prev Apr 2010; 19 (4):1000-3. http://dx.doi.org/10.1158/1055-9965.EPI-10-0044.
48. Pickrell WO, Rees MI, Chung SK. Next generation sequencing methodologies-an overview. Adv Protein Chem Struct Biol 2012; 89:1-26. http://dx.doi.org/10.1016/B978-0-12-394287-6.00001-X.
49. McArt DG, Dunne PD, et al. Connectivity mapping for candidate therapeutics identification using next generation sequencing RNA-Seq data. PLoS One Jun 26 2013; 8 (6):e66902.
50. Marquardt JU, Andersen JB. Next-generation sequencing: application in liver cancer-past, present and future? Biology (Basel) Aug 31 2012; 1 (2):383-94.
51. Liu B, Morrison CD, et al. Computational methods for detecting copy number variations in cancer genome using next generation sequencing: principles and challenges. Oncotarget Nov 2013; 4 (11):1868-81.
52. Illimina. An introduction to next generation sequencing. http://res.illumina.com/documents/products/illumina-sequencing-introduction.pdf.
53. Qian X, Ba Y, Zhuang Q., Zhong G. RNA-Seq technology and its application in fish transcriptomics. OMICS Dec 31 2013; 18 (2):98-110. http://dx.doi.org/10.1089/omi.2013.0110 [Epub 2013 Dec 31].
54. El-Metwally S, Hamza T, et al. Next-generation sequence assembly: four stages of data processing and computational challenges. PLoS Comput Biol Dec 2013; 9 (12):e1003345. http://dx.doi.org/10.1371/journal.pcbi.1003345.
55. Sims D, Ilott NE, et al. CGAT: computational genomics analysis toolkit. Bioinformatics Jan 5 2014; 30 (9):1290-1. http://dx.doi.org/10.1093/bioinformatics/btt756 [Epub 2014 Jan 5].
56. Ayers KL, Cordell HJ. Identification of grouped rare and common variants via penalized logistic regression. Genet Epidemiol Sep 2013; 37 (6):592-602. http:// dx.doi.org/10.1002/gepi.21746 [Epub 2013 Jul 8].
57. Phimister EG, Feero WG, Guttmacher AE. Realizing genomic medicine. N EnglJ Med Feb 23 2012; 366 (8):757-9. http://dx.doi.org/10.1056/NEJMe1200749.
58. Feero WG, Guttmacher AE, Collins FS. Genomic medicine-an updated primer. N Engl J Med May 27 2010; 362 (21):2001-11. http://dx.doi.org/10.1056/NEJMra0907175.
59. Chang F, Li MM. Clinical application of amplicon-based next-generation sequencing in cancer. Cancer Genet Oct 11 2013. http://dx.doi.org/10.1016/j.cancergen.2013.10.003 [pii: S2210-7762(13)00142-7].
60. Labidi-Galy SI, Clauss A, et al. Elafin drives poor outcome in high-grade serous ovarian cancers and basal-like breast tumors. Oncogene 2014 Jan 27. http://dx.doi.org/10.1038/onc.2013.562.
61. Macconaill LE, Garraway LA. Clinical implications of the cancer genome. J Clin Oncol Dec 10 2010; 28 (35):5219-28. http://dx.doi.org/10.1200/JCO.2009.27.4944 [Epub 2010 Oct 25].
62. Shin SC, Kim G, Yang H.B., Park KW, Kang BC, Park HG. Application of the ASLP technology to a novel platform for rapid and noise-free multiplexed SNP genotyping. Biosens Bioelectron Nov 20 2013; 54C:687-94. http://dx.doi.org/10.1016/j.bios.2013.10.071.
63. Rowe LR, Bentz BG, Bentz JS. Detection of BRAF V600E activating mutation in papillary thyroid carcinoma using PCR with allele-specific fluorescent probe melting curve analysis. J Clin Pathol Nov 2007; 60 (11):1211-5.
64. Badalian-Very G, Vergilio JA, Fleming M, Rollins BJ. Pathogenesis of Langerhans cell histiocytosis. Annu Rev Pathol Jan 24 2013; 8:1-20. http://dx.doi.org/10.1146/annurev-pathol-020712-163959 [Epub 2012 Aug 6].
65. Badalian-Very G, Vergilio JA, Degar B.A., Rodriguez-Galindo C, Rollins BJ. Recent advances in the understanding of Langerhans cell histiocytosis. Br J Haematol Jan 2012; 156 (2): 163-72. http://dx.doi.org/10.1111/j.1365-2141.2011.08915.x [Epub 2011 Oct 24].
66. Satoh T, Smith A, et al. RAF mutant alleles associated with Langerhans cell histiocytosis, a granulomatous pediatric disease. PLoS One 2012; 7 (4):e33891. http://dx.doi.org/10.1371/journal.pone.0033891 [Epub 2012 Apr 10].
67. Thomas RK, Baker AC, et al. High-throughput oncogene mutation profiling in human cancer. Nat Genet Mar 2007; 39 (3):347-51 [Epub 2007 Feb 11].
68. Badalian-Very G. A common progenitor cell in LCH and ECD. Blood 2014 Aug 14; 124 (7):991-2. http://dx.doi.org/10.1182/blood-2014-06-581736.
69. Cancer genome atlas research network, Weinstein JN, et al. The Cancer Genome Atlas Pan-Cancer analysis project. Nat Genet Oct 2013; 45 (10):1113-20. http://dx.doi.org/10.1038/ng.2764.
70. Turner EH, Lee C, Ng S.B., Nickerson DA, Shendure J. Massively parallel exon capture and library-free resequencing across 16 genomes. Nat Methods May 2009; 6 (5): 315-6. http://dx.doi.org/10.1038/nmeth.f.248 [Epub 2009 Apr 6].
71. Tewhey R, Warner JB, et al. Microdroplet-based PCR enrichment for large-scale targeted sequencing. Nat Biotechnol Nov 2009; 27 (11):1025-31. http://dx.doi.org/10.1038/nbt.1583 [Epub 2009 Nov 1].
72. Lonigro RJ, Grasso CS, et al. Detection of somatic copy number alterations in cancer using targeted exome capture sequencing. Neoplasia Nov 2011; 13 (11):1019-25.
73. Benson III AB. Data acquisition, tumor heterogeneity and precision medicine: future challenges for oncologic comparative effectiveness research. J Comp Eff Res Jan 2013; 2 (1):17-21. http://dx.doi.org/10.2217/cer.12.76.
74. Badalian G, Barbai T, Derecskei K., Szendrôi M, Tímár J. Phenotype of bone metastases of non-small cell lung cancer: epidermal growth factor receptor expression and K-RAS mutational status. Pathol Oncol Res 2007; 13 (2):99-104 [Epub 2007 Jul 3].
75. Michor F, Polyak K. The origins and implications of intratumor heterogeneity. Cancer Prev Res (Phila) Nov 2010; 3 (11):1361-4. http://dx.doi.org/10.1158/1940-6207.CAPR-10-0234 [Epub 2010 Oct 19].
76. Wang Z, Gerstein M, Snyder M. RNA-Seq: a revolutionary tool for transcriptomics. Nat Rev Genet Jan 2009; 10 (1):57-63. http://dx.doi.org/10.1038/nrg2484.
77. Hammerman PS, Lawrence MS, et al. Comprehensive genomic characterization of squamous cell lung cancers. Cancer genome atlas research network. Nature Sep 27 2012; 489 (7417):519-25. http://dx.doi.org/10.1038/nature11404 [Epub 2012 Sep 9].
78. Maher CA, Palanisamy N, et al. Chimeric transcript discovery by paired-end transcriptome sequencing. Proc Natl Acad Sci U S A Jul 28 2009; 106 (30):12353-8. http://dx.doi.org/10.1073/pnas.0904720106 [Epub 2009 Jul 10].
79. Padilla J, Jenkins NT, et al. Transcriptome-wide RNA sequencing analysis of rat skeletal muscle feed arteries. Part II: impact of exercise training in obesity. J Appl Physiol (1985) Jan 9 2014; 7 (2):e00225. http://dx.doi.org/10.1002/phy2.225e Collection 2014 Feb 1.
80. FANTOM Consortium, Suzuki H, et al. The transcriptional network that controls growth arrest and differentiation in a human myeloid leukemia cell line. Nat Genet May 2009; 41 (5):553-62. http://dx.doi.org/10.1038/ng.375 [Epub 2009 Apr 19].
81. Fujisawa S, Nakamae H, et al. Efficacy and safety of dasatinib versus imatinib in Japanese patients with newly diagnosed chronic-phase chronic myeloid leukemia (CML-CP): subset analysis of the DASISION trial with 2-year follow-up. Int J Hematol Dec 20 2013; 99 (2):141-53. http://dx.doi.org/10.1007/s12185-013-1470-1 [Epub 2013 Dec 20].
82. Schiffer CA. Which TKI should be recommended as initial treatment for CML in chronic phase? Oncology (Williston Park) Oct 2012; 26 (10):912[914].
83. Zhao R, Follows GA, et al. Inhibition of the Bcl-xL deamidation pathway in myelo-proliferative disorders. N Engl J Med Dec 25 2008; 359 (26):2778-89. http://dx.doi.org/10.1056/NEJMoa0804953.
84. Jabbour E, Cortes J, Ravandi F., O'Brien S, Kantarjian H. Targeted therapies in hema-tology and their impact on patient care: chronic and acute myeloid leukemia. Semin Hematol Oct 2013; 50 (4):271-83. http://dx.doi.org/10.1053/j.seminhematol.2013.09.006 (Epub 2013 Oct 3).
85. Verheul HM, Pinedo HM. Possible molecular mechanisms involved in the toxicity of angiogenesis inhibition. Nat Rev Cancer Jun 2007; 7 (6):475-85.
86. Belum VR, Fontanilla Patel H. Skin toxicity of targeted cancer agents: mechanisms and intervention. Future Oncol Aug 2013; 9 (8):1161-70. http://dx.doi.org/10.2217/fon.13.62.
87. Balagula Y, Rosen ST, Lacouture ME. The emergence of supportive oncodermatology: the study of dermatologic adverse events to cancer therapies. J Am Acad Dermatol Sep 2011; 65 (3):624-35. http://dx.doi.org/10.1016/j.jaad.2010.06.051 [Epub 2011 Jul 20].
88. Boone SL, Rademaker A, Liu D., Pfeiffer C, Mauro DJ, Lacouture ME. Impact and management of skin toxicity associated with anti-epidermal growth factor receptor therapy: survey results. Oncology 2007; 72 (3-4):152-9 [Epub 2007 Dec 21].
89. Shaw AT, Hsu PP, Awad M.M., Engelman JA. Tyrosine kinase gene rearrangements in epithelial malignancies. Nat Rev Cancer Nov 2013; 13 (11):772-87. http://dx.doi.org/10.1038/nrc3612 [Epub 2013 Oct 17].
90. Soverini S, Branford S, et al. Implications of BCR-ABL1 kinase domain-mediated resistance in chronic myeloid leukemia. Leuk Res Jan 2014; 38 (1):10-20. http:// dx.doi.org/10.1016/j.leukres.2013.09.011 [Epub 2013 Sep 23].
91. Zhang J, Yang PL. Targeting cancer with small molecule kinase inhibitors. Nat Rev Cancer Jan 2009; 9 (1):28-39. http://dx.doi.org/10.1038/nrc2559.
92. Yang SH. Molecular basis of drug resistance: epidermal growth factor receptor tyrosine kinase inhibitors and anaplastic lymphoma kinase inhibitors. Tuberc Respir Dis (Seoul) Nov 2013; 75 (5):188-98 [Epub 2013 Nov 29].
93. Gomez GG, Wykosky J, Zanca C., Furnari FB, Cavenee WK. Therapeutic resistance in cancer: microRNA regulation of EGFR signaling networks. Cancer Biol Med Dec 2013; 10 (4):192-205.
94. Dibb NJ, Dilworth SM, et al. Switching on kinases: oncogenic activation of BRAF and the PDGFR family. Nat Rev Cancer Sep 2004; 4 (9):718-27.
95. Greuber EK, Smith-Pearson P, Wang J., Pendergast AM. Role of ABL family kinases in cancer: from leukaemia to solid tumours. Nat Rev Cancer Aug 2013; 13 (8):559-71. http://dx.doi.org/10.1038/nrc3563 [Epub 2013 Jul 11].
96. Seton-Rogers S. Oncogenes: direct hit on mutant RAS. Nat Rev Cancer Jan 2014; 14 (1):8-9. http://dx.doi.org/10.1038/nrc3650 [Epub 2013 Dec 5].
97. Ross JS, Symmans WF, Pusztai L, Hortobagyi GN. Pharmacogenomics and clinical biomarkers in drug discovery and development. Am J Clin Pathol Dec 2005; 124: S29-41 [Suppl.].
98. Marton MJ, Weiner R. Practical guidance for implementing predictive biomarkers into early phase clinical studies. Biomed Res Int 2013; 2013:891391. http://dx.doi.org/10.1155/2013/891391 [Epub 2013 Oct 22].
99. ∗35 is determined bythe impaired interaction with P450 oxidoreductase. Pharmacogenomics J Dec 10 2013. http://dx.doi.org/10.1038/tpj.2013.41.
100. Ye C, Jin H, Zhang R., et al. Variability of warfarin dose response associated with CYP2C9 and VKORC1 gene polymorphisms in Chinese patients. J Int Med Res Feb 2013; 42 (1):67-76. http://dx.doi.org/10.1177/0300060513499094 [Epub 2013 Nov 28].
101. Lee MT, Klein TE. Pharmacogenetics of warfarin: challenges and opportunities. J Hum Genet Jun 2013; 58 (6):334-8. http://dx.doi.org/10.1038/jhg.2013.40 [Epub 2013 May 9].
102. Dotson WD, Douglas MP, et al. Prioritizing genomic applications for action by level of evidence: a horizon-scanning method. Clin Pharmacol Ther Nov 14 2013. http:// dx.doi.org/10.1038/clpt.2013.226.
103. Emadi A, Karp JE. The clinically relevant pharmacogenomic changes in acute myelogenous leukemia. Pharmacogenomics Aug 2012; 13 (11):1257-69.
104. Lawrence MS, Stojanov P, et al. Mutational heterogeneity in cancer and the search for new cancer-associated genes. Nature Jul 11 2013; 499 (7457):214-8. http://dx.doi.org/10.1038/nature12213 [Epub 2013 Jun 16].
105. Lôrincz T, Tóth J, Badalian G., Tímár J, Szendrôi M. HER-2/neu genotype of breast cancer may change in bone metastasis. Pathol Oncol Res 2006; 12 (3):149-52 [Epub 2006 Sep 23].
106. Badalian G, Derecskei K, Szendroi A., Szendroi M, Timar J. EGFR and VEGRFR protein expression in bone metastases of clear cell renal cancer. Anticancer Res Mar-Apr 2007; 27 (2):889-94.
107. Marusyk A, Polyak K. Cancer. Cancer cell phenotypes, in fifty shades of grey. Science Feb 1 2013; 339 (6119):528-9.
108. Lynch Jr TJ, Kim ES, Eaby B, Garey J., West DP, Lacouture ME. Epidermal growth factor receptor inhibitor-associated cutaneous toxicities: an evolving paradigm in clinical management. Oncologist May 2007; 12 (5):610-21.
109. Scripture CD, Figg WD, Sparreboom A. Peripheral neuropathy induced by paclitaxel: recent insights and future perspectives. Curr Neuropharmacol Apr 2006; 4 (2):165-72.
110. Haroche J, Charlotte F, et al. High prevalence of BRAF V600E mutations in Erdheim-Chester disease but not in other non-Langerhans cell histiocytoses. Blood Sep 27 2012; 120 (13):2700-3 [Epub 2012 Aug 9].
111. Scripture CD, Sparreboom A, Figg WD. Modulation of cytochrome P450 activity: implications for cancer therapy. Lancet Oncol Oct 2005; 6 (10):780-9.
112. Allen CE, McClain KL. Erdheim-Chester: beyond the lesion. Blood Mar 10 2011; 117 (10):2745-6. http://dx.doi.org/10.1182/blood-2011-01-330233.
113. Seton-Rogers S. Multiple myeloma: destruction of Ikaros. Nat Rev Cancer Dec 23 2013; 14 (1):9. http://dx.doi.org/10.1038/nrc3663.
114. Valencia PM, Farokhzad OC, Rhee M, Langer R., Farokhzad OC, Karnik R. Microfluidic technologies for accelerating the clinical translation of nanoparticles. Nat Nanotechnol Oct 2012; 7 (10):623-9. http://dx.doi.org/10.1038/nnano.2012.168.
115. Valencia PM, Pridgen EM, et al. Microfluidic platform for combinatorial synthesis and optimization of targeted nanoparticles for cancer therapy. ACS Nano Dec 23 2013; 7 (12):10671-80. http://dx.doi.org/10.1021/nn403370e [Epub 2013 Nov 11].
116. Hydbring P, Badalian-Very G. Clinical applications of microRNAs. Version 3. F1000Res; 2013 Jun 6 [revised 2013 Oct 8]; 2:136. http://dx.doi.org/10.12688/f1000research.2-136.v3eCollection2013.
117. Goldberg M, Langer R, Jia X. Nanostructured materials for applications in drug delivery and tissue engineering. J Biomater Sci Polym Ed 2007; 18 (3):241-68.
118. Salvador-Morales C, Valencia PM, Gao W, Karnik R., Farokhzad OC. Recent developments in multifunctional hybrid nanoparticles: opportunities and challenges in cancer therapy. Front Biosci (Elite Ed) Jan 1 2012; 4:529-45.
119. Ferrari R, Lupi M, et al. Integrated multiplatform method for in vitro quantitative assessment of cellular uptake for fluorescent polymer nanoparticles. Nanotechnology Jan 7 2014; 25 (4):045102.
120. De Jong WH, Borm PJ. Drug delivery and nanoparticles: applications and hazards. Int J Nanomedicine 2008; 3 (2):133-49.
121. Gerber A, Bundschuh M, Klingelhofer D., Groneberg DA. Gold nanoparticles: recent aspects for human toxicology. J Occup Med Toxicol Dec 11 2013; 8 (1):32. http://dx.doi.org/10.1186/1745-6673-8-32.
122. Vandebriel RJ, De Jong WH. A review of mammalian toxicity of ZnO nanoparticles. Nanotechnol Sci Appl Aug 15 2012; 5:61-71.
123. Elsabahy M, Zhang S, et al. Surface charges and shell crosslinks each play significant roles in mediating degradation, biofouling, cytotoxicity and immunotoxicity for polyphosphoester-based nanoparticles. Sci Rep Nov 22 2013; 3:3313. http://dx.doi.org/10.1038/srep03313.
124. Polat BE, Blankschtein D, Langer R. Low-frequency sonophoresis: application to the transdermal delivery of macromolecules and hydrophilic drugs. Expert Opin Drug Deliv Dec 2010; 7 (12):1415-32. http://dx.doi.org/10.1517/17425247.2010.538679.
125. Ferrari R, Colombo C, et al. Synthesis of surfactant free PCL-PEG brushed nanopar-ticles with tunable degradation kinetics. Int J Pharm Sep 10 2013; 453 (2):551-9. http://dx.doi.org/10.1016/j.ijpharm.2013.06.020 [Epub 2013 Jun 21].
126. Gao W, Hu CM, Fang R.H., Zhang L. Liposome-like nanostructures for drug delivery. J Mater Chem B Mater Biol Med Dec 2013; 28:1 (48). http://dx.doi.org/10.1039/C3TB21238F.
127. Guadagnini R, Moreau K, Hussain S., Marano F, Boland S. Toxicity evaluation of engineered nanoparticles for medical applications using pulmonary epithelial cells. Nanotoxicology Nov 29 2013 [Epub ahead of print].
128. Kwon S, Yang YS. Nasal and pulmonary toxicity of titanium dioxide nanoparticles in rats. Toxicol Res Dec 2012; 28 (4):217-24. http://dx.doi.org/10.5487/TR.2012.28.4.217.
129. Scott R, Crabbe D, Krynska B., Ansari R, Kiani MF. Aiming for the heart: targeted delivery of drugs to diseased cardiac tissue. Expert Opin Drug Deliv Nov, 2013; 5 (4):459-70.
130. Vaudana Elisabetta. The innovative medicine initiative: a public private partnership model to foster drug discovery. Comput Struct Biotechnol J 2013; 6 (7) [e.201303017].
131. Lounnas Valere, Ritschel Tina, Kelder J, McGuire R., Bywater RP, Foloppe N. Current progress in structure-based rational drug design marks a new mindset in drug discovery. Comput Struct Biotechnol J 2013; 5 (6) [e.201302011].
132. Hopkins AL, Groom CR. The drugable genome. Nat Rev Discov Sep 2002; 1 (9): 727-30.