Aptamers are single-stranded synthetic DNA- or RNA-based oligonucleotides that fold into various shapes to bind to a specific target, which includes proteins, metals, and molecules. Aptamers have high affinity and high specificity that are comparable to that of antibodies. They are obtained using iterative method, called (Systematic Evolution of Ligands by Exponential Enrichment) SELEX and cell-based SELEX (cell-SELEX). Aptamers can be paired with recent advances in nanotechnology, microarray, microfluidics, and other technologies for applications in clinical medicine. One particular area that aptamers can shed a light on is biomarker discovery. Biomarkers are important in diagnosis and treatment of cancer. In this paper, we will describe ways in which aptamers can be used to discover biomarkers for cancer diagnosis and therapeutics. 1. Introduction Approximately 1.5 million Americans were diagnosed with cancer in 2010 [1]. Malignant neoplasm is the second leading cause of death in the world and the leading cause of death in developed nations [2]. Chemotherapy is a common method of treating cancer, but it is largely indiscriminate in that it does not target cancer cells with specificity. Therefore, considerable interest has been shown in developing novel treatments that target only cancer cells, thus avoiding the toxicity of chemotherapy against normal tissues adjacent to the tumor. Such targets can be cancer-specific biomarkers that may be used to assess the changes in expression states of certain proteins or genes within a primary tumor. Since genetic mutations play a key role in modulating the maintenance and progression of cancer cells, fundamental differences in protein levels or gene expression states can be exploited and used for diagnostics and therapies [3]. This paper aims to shed light on the possibility of utilizing aptamers for the discovery of crucial biomarkers for cancers with the goal of improving early-stage diagnosis and therapy. In recent years, interest has been shown in using aptamers to develop cancer treatments. Currently, AS1411 [4, 5], a potential therapeutic for acute myeloid leukaemia, and NOX-A12 [6, 7], a potential therapeutic for multiple myeloma and non-Hodgkin’s lymphoma, aptamers developed by Antisoma and NOXXON, respectively, are in clinical trials [8]. Aptamers are single-stranded oligonucleotides that act like antibodies in recognizing molecular moieties like biomarkers [9]. Because of their ability to fold into secondary or tertiary shapes, aptamers can bind to a wide range of targets, such as metals, proteins,
References
[1]
C. D. Medley, S. Bamrungsap, W. Tan, and J. E. Smith, “Aptamer-conjugated nanoparticles for cancer cell detection,” Analytical Chemistry, vol. 83, no. 3, pp. 727–734, 2011.
[2]
J. Temsamani and P. Vidal, “The use of cell-penetrating peptides for drug delivery,” Drug Discovery Today, vol. 9, no. 23, pp. 1012–1019, 2004.
[3]
W. C. Hahn, C. M. Counter, A. S. Lundberg, R. L. Beijersbergen, M. W. Brooks, and R. A. Weinberg, “Creation of human tumour cells with defined genetic elements,” Nature, vol. 400, no. 6743, pp. 464–468, 1999.
[4]
P. J. Bates, D. A. Laber, D. M. Miller, S. D. Thomas, and J. O. Trent, “Discovery and development of the G-rich oligonucleotide AS1411 as a novel treatment for cancer,” Experimental and Molecular Pathology, vol. 86, no. 3, pp. 151–164, 2009.
[5]
E. Merit Reyes-Reyes, Y. Teng, and P. J. Bates, “A new paradigm for aptamer therapeutic AS1411 action: uptake by macropinocytosis and its stimulation by a nucleolin-dependent mechanism,” Cancer Research, vol. 70, no. 21, pp. 8617–8629, 2010.
[6]
S. G. Sayyed, H. H？gele, O. P. Kulkarni, et al., “Podocytes produce homeostatic chemokine stromal cell-derived factor-1/CXCL12, which contributes to glomerulosclerosis, podocyte loss and albuminuria in a mouse model of type 2 diabetes,” Diabetologia, vol. 52, no. 11, pp. 2445–2454, 2009.
[7]
M. N. Darisipudi, O. P. Kulkarni, S. G. Sayyed, et al., “Dual blockade of the homeostatic chemokine CXCL12 and the proinflammatory chemokine CCL2 has additive protective effects on diabetic kidney disease,” The American Journal of Pathology, vol. 179, no. 1, pp. 116–124, 2011.
[8]
A. D. Keefe, S. Pai, and A. Ellington, “Aptamers as therapeutics,” Nature Reviews Drug Discovery, vol. 9, no. 7, pp. 537–550, 2010.
[9]
D. Hwang, H. Ko, J. Lee et al., “A nucelolin-targeted multimodal nanoparticle imaging probe for tracking cancer cells using an aptamer,” Journal of Nuclear Medicine, vol. 51, pp. 98–105, 2010.
[10]
X. Fang and W. Tan, “Aptamers generated from cell-SELEX for molecular medicine: a chemical biology approach,” Accounts of Chemical Research, vol. 43, no. 1, pp. 48–57, 2010.
[11]
N. L. Henry and D. F. Hayes, “Cancer biomarkers,” Molecular Oncology, vol. 6, no. 2, pp. 140–146, 2012.
[12]
M. Mann and O. N. Jensen, “Proteomic analysis of post-translational modifications,” Nature Biotechnology, vol. 21, no. 3, pp. 255–261, 2003.
[13]
W. Hancock, A. Apffel, J. Chakel et al., “Integrated genomic/proteomic analysis,” Analytical Chemistry, vol. 71, no. 21, pp. 742A–748A, 1999.
[14]
L. Gold, D. Ayers, J. Bertino, et al., “Aptamer-based multiplexed proteomic technology for biomarker discovery,” PLoS ONE, vol. 5, no. 11, artcile e15004, 2010.
[15]
K. Sefah, D. Shangguan, X. Xiong, M. B. O’Donoghue, and W. Tan, “Development of DNA aptamers using Cell-SELEX,” Nature Protocols, vol. 5, no. 6, pp. 1169–1185, 2010.
[16]
D. Shangguan, Z. Cao, L. Meng et al., “Cell-specific aptamer probes for membrane protein elucidation in cancer cells,” Journal of Proteome Research, vol. 7, no. 5, pp. 2133–2139, 2008.
[17]
D. Shangguan, Y. Li, Z. Tang et al., “Aptamers evolved from live cells as effective molecular probes for cancer study,” Proceedings of the National Academy of Sciences of the United States of America, vol. 103, no. 32, pp. 11838–11843, 2006.
[18]
D. A. Daniels, H. Chen, B. J. Hicke, K. M. Swiderek, and L. Gold, “A tenascin-C aptamer identified by tumor cell SELEX: Systematic evolution of ligands by exponential enrichment,” Proceedings of the National Academy of Sciences of the United States of America, vol. 100, no. 26, pp. 15416–15421, 2003.
[19]
R. Chiquet-Ehrismann, E. J. Mackie, C. A. Pearson, and T. Sakakura, “Tenascin: an extracellular matrix protein involved in tissue interactions during fetal development and oncogenesis,” Cell, vol. 47, no. 1, pp. 131–139, 1986.
[20]
J. Yoshida, T. Wakabayashi, S. Okamoto et al., “Tenascin in cerebrospinal fluid is a useful biomarker for the diagnosis of brain tumour,” Journal of Neurology, Neurosurgery and Psychiatry, vol. 57, no. 10, pp. 1212–1215, 1994.
[21]
K. E. Wilson, S. P. Langdon, A. M. Lessells, and W. R. Miller, “Expression of the extracellular matrix protein tenascin in malignant and benign ovarian tumours,” British Journal of Cancer, vol. 74, no. 7, pp. 999–1004, 1996.
[22]
R. M. Ostroff, W. L. Bigbee, W. Franklin, et al., “Unlocking biomarker discovery: large scale application of aptamer proteomic technology for early detection of lung cancer,” PLoS ONE, vol. 5, no. 12, article e15003, 2010.
[23]
T. Kunii, S. I. Ogura, M. Mie, and E. Kobatake, “Selection of DNA aptamers recognizing small cell lung cancer using living cell-SELEX,” Analyst, vol. 136, no. 7, pp. 1310–1312, 2011.
[24]
T. Cavalier-Smith, “Membranome and membrane heredity in development and evolution,” in Organelles, Genomes and Eukaryote Phylogeny an Evolutionary Synthesis in the Age of Genomics, R. P. Hirt and D. S. Horner, Eds., 2012.
[25]
D. Ghosh, R. C. Beavis, and J. A. Wilkins, “The identification and characterization of membranome components,” Journal of Proteome Research, vol. 7, no. 4, pp. 1572–1583, 2008.
[26]
P. Dua, S. Kim, and D. K. Lee, “Nucleic acid aptamers targeting cell-surface proteins,” Methods, vol. 54, no. 2, pp. 215–225, 2011.
[27]
F. Tanaka, K. Yoneda, N. Kondo et al., “Circulating tumor cell as a diagnostic marker in primary lung cancer,” Clinical Cancer Research, vol. 15, no. 22, pp. 6980–6986, 2009.
[28]
P. Cen, X. Ni, J. Yang, D. Y. Graham, and M. Li, “Circulating tumor cells in the diagnosis and management of pancreatic cancer,” Biochimica et Biophysica Acta, vol. 1826, no. 2, pp. 350–356, 2012.
[29]
J. B. Welsh, L. M. Sapinoso, S. G. Kern et al., “Large-scale delineation of secreted protein biomarkers overexpressed in cancer tissue and serum,” Proceedings of the National Academy of Sciences of the United States of America, vol. 100, no. 6, pp. 3410–3415, 2003.
[30]
C. D. Medley, S. Bamrungsap, W. Tan, and J. E. Smith, “Aptamer-conjugated nanoparticles for cancer cell detection,” Analytical Chemistry, vol. 83, no. 3, pp. 727–734, 2011.
[31]
G. Mayer, M. S. L. Ahmed, A. Dolf, E. Endl, P. A. Knolle, and M. Famulok, “Fluorescence-activated cell sorting for aptamer SELEX with cell mixtures,” Nature Protocols, vol. 5, no. 12, pp. 1993–2004, 2010.
[32]
S. M. Douglas, I. Bachelet, and G. M. Church, “A logic-gated nanorobot for transport of molecular payload,” Science, vol. 355, no. 6070, pp. 831–834, 2012.
[33]
D. Sangguan, Y. Li, Z. Tang, et al., “Aptamers evolved from live cells as effective molecular probes for cancer study,” Proceedings of the National Academy of Sciences of the United States of America, vol. 103, no. 32, pp. 11838–11843, 2006.
[34]
S. Bamford, E. Dawson, S. Forbes et al., “The COSMIC (Catalogue of Somatic Mutations in Cancer) database and website,” British Journal of Cancer, vol. 91, no. 2, pp. 355–358, 2004.
[35]
http://www.sanger.ac.uk/genetics/CGP/cosmic/.
[36]
L. E. MacConaill, C. D. Campbell, S. M. Kehoe et al., “Profiling critical cancer gene mutations in clinical tumor samples,” PLoS ONE, vol. 4, no. 11, article e7887, 2009.
[37]
P. S. Hammerman, D. N. Hayes, M. D. Wilkerson, et al., “Comprehensive genomic characterization of squamous cell lung cancers,” Nature, vol. 489, pp. 519–525, 2012.
[38]
T. Cancer and G. Atlas, “Comprehensive molecular characterization of human colon and rectal cancer,” Nature, vol. 487, pp. 330–337, 2012.
[39]
R. McLendon, A. Friedman, D. Bigner et al., “Comprehensive genomic characterization defines human glioblastoma genes and core pathways,” Nature, vol. 455, no. 7216, pp. 1061–1068, 2008.
[40]
D. C. Koboldt, R. S. Fulton, M. D. McLellan, et al., “Comprehensive molecular portraits of human breast tumours,” Nature, pp. 1–10, 2012.
[41]
T. C. Larman, S. R. DePalma, A. G. Hadjipanayisa, et al., “Spectrum of somatic mitochondrial mutations in five cancers,” Proceedings of the National Academy of Sciences of the United States of America, vol. 109, pp. 14087–14091, 2012.
