Skip to main content

Advertisement

SpringerLink
Log in

Novel biotechnology approaches in colorectal cancer diagnosis and therapy

  • Review
  • Published:
Biotechnology Letters Aims and scope Submit manuscript

Abstract

With ever-increasing molecular information about colorectal cancer (CRC), there is an expectation to detect more sensitive and specific molecular markers for new advanced diagnostic methods that can surpass the limitations of current screening tests. Moreover, enhanced molecular pathology knowledge about cancer has led to the development of targeted therapies, designed to interfere with specific aberrant biological pathways in cancer. Furthermore, biotechnology has opened a new window in CRC diagnosis and treatment by introducing different application of antibodies, antibody fragments, non-Ig scaffold proteins, and aptamers in targeted therapy and drug delivery. This review summarizes the molecular diagnostic and therapeutic approaches in CRC with a focus on genetic and epigenetic alterations, protein and metabolite markers as well as targeted therapy and drug delivery by Ig-scaffold proteins, non-Ig scaffold proteins, nanobodies, and aptamers.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Abbreviations

AMER1:

APC membrane recruitment 1

APC:

Adenomatous polyposis coli

APC2:

Adenomatosis polyposis coli 2

ARMS:

Amplification refractory mutation system

CEA:

Carcino embryonic antigen

CDKN2A:

Cyclin-dependent kinase inhibitor 2a

CE:

Capillary electrophoresis

CHIP:

Chromatin immunoprecipitation

CIMP:

CpG island methylator phenotype

CIN:

Chromosomal instability

CRC:

Colorectal cancer

CSC:

Cancer stem cell

CTAs:

Cancer testis antigens

DNMTs:

DNA methyltransferases

DLL4:

DLL4 delta-like ligand 4

Dox:

Doxorubicin

EGFR:

Epithelial growth factor receptor

(EpCAM):

Epithelial cell adhesion molecule

ErbB:

Erythroblastosis oncogene b

EZH2:

Enhancer of zeste homolog 2

FIT:

Fecal immunochemical test

FOBT:

Faecal occult blood test

gFOBT:

Guaiac-based fecal occult blood test

HGF:

Hepatocyte growth factor

HPLC:

High performance liquid chromatography

IGF-1R:

Insulin-like growth factor 1 receptor

ITGA4:

Integrin subunit alpha 4

K-Ras:

Kirsten rat sarcoma viral oncogene homologue

LINE-1:

Long interspersed nuclear element 1

MAPK:

Mitogen-activated protein kinase

Methyl-BEAMing:

Methyl-beads, emulsion, amplification and magnetics

MGMT:

Methyl guanine methyl transferase

MLH1:

MutL homolog 1

MMR:

Mismatch repair

MMR:

Macrophage mannose receptor

MS-AFLP:

Methylation-sensitive amplification length polymorphism

MS-MLPA:

Methylation-specific multiplex ligation-dependent probe amplification

MSP:

Methylation specific PCR

MSI:

Microsatellite instability

NK:

Natural killer

PTMs:

Post-translational modifications

PKCB:

Protein kinase C beta

PI3K:

Phosphatidyl inositol 3-kinase

SAM:

S-(adenosyl)-methionine

SEREX:

Serologic identification of antigens by recombinant expression

SELEX:

Systematic evolution of ligands by exponential enrichment

SERPA:

Serological proteome analysis

SFRP2:

Secreted frizzled-related protein 2

SINE:

Short interspersed nuclear elements

SPECT:

Single-photon emission computed tomography

TAAs:

Tumor-associated antigens

TGF-β:

Transforming growth factor beta

UCH-L3:

Ubiquitin C-terminal hydrolase l3

UPLC:

Ultra performance liquid chromatography

UTR:

Un-translated region

VEGF:

Vascular endothelial growth factor

VOCs:

Volatile organic compounds

WNT:

Wingless transduction

References

  • Altintas I, Heukers R, Van der Meel R, Lacombe M et al (2013) Nanobody-albumin nanoparticles (NANAPs) for the delivery of a multikinase inhibitor 17864 to EGFR overexpressing tumor cells. J Contr Release 165:110–118

    Article  CAS  Google Scholar 

  • Barker N, Clevers H (2010) Leucine-rich repeat-containing G-protein-coupled receptors as markers of adult stem cells. Gastroenterology 138:1681–1696

    Article  CAS  PubMed  Google Scholar 

  • Bertotti A, Papp E, Jones S, Adleff V et al (2015) The genomic landscape of response to EGFR blockade in colorectal cancer. Nature 526:263–267

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bibikova M, Lin Z, Zhou L, Chudin E et al (2006) High-throughput DNA methylation profiling using universal bead arrays. Genome Res 16:383–393

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bibikova M, Le J, Barnes B, Saedinia-Melnyk S et al (2009) Genome-wide DNA methylation profiling using Infinium® assay. Epigenomics 1:177–200

    Article  CAS  PubMed  Google Scholar 

  • Bibikova M, Barnes B, Tsan C, Ho V et al (2011) High density DNA methylation array with single CpG site resolution. Genomics 98:288–295

    Article  CAS  PubMed  Google Scholar 

  • Boersma YL, Chao G, Steiner D, Wittrup KD, Plückthun A (2011) Bispecific designed ankyrin repeat proteins (DARPins) targeting epidermal growth factor receptor inhibit A431 cell proliferation and receptor recycling. J Biol Chem 286:41273–41285

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bostad M, Berg K, Hogset A, Skarpen E et al (2013) Photochemical internalization (PCI) of immunotoxins targeting CD133 is specific and highly potent at femtomolar levels in cells with cancer stem cell properties. J Contr Release 168:317–326

    Article  CAS  Google Scholar 

  • Brim H, Abu-Asab M, Nouraie S, Salazar M et al (2014) An integrative CGH, MSI and candidate genes methylation analysis of colorectal tumors. PLoS ONE 9:e82185

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Broadbridge VT, Karapetis CS, Price TJ (2012) Cetuximab in metastatic colorectal cancer. Exp Rev Anticancer 12:555–565

    Article  CAS  Google Scholar 

  • Bush S (2002) Monoclonal antibodies conjugated with radioisotopes for the treatment of Non-Hodgkin’s lymphoma. Semin Oncol Nurs 18:16–21

    Article  PubMed  Google Scholar 

  • Byrne H, Conroy PJ, Whisstock JC, O’Kennedy RJ (2013) A tale of two specificities: bispecific antibodies for therapeutic and diagnostic applications. Trends Biotechnol 31:621–632

    Article  CAS  PubMed  Google Scholar 

  • Calin GA, Dumitru CD, Shimizu M, Bichi R et al (2002) Frequent deletions and down-regulation of micro-RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia. Proc Natl Acad Sci USA 99:15524–15529

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Calin GA, Sevignani C, Dumitru CD, Hyslop T et al (2004) Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. Proc Natl Acad Sci USA 101:2999–3004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cardoso MM, Peca IN, Roque AC (2012) Antibody-conjugated nanoparticles for therapeutic applications. Curr Med Chem 19:3103–3127

    Article  CAS  PubMed  Google Scholar 

  • Carroll MR, Seaman HE, Halloran SP (2014) Tests and investigations for colorectal cancer screening. Clin Biochem 47:921–939

    Article  CAS  PubMed  Google Scholar 

  • Carter PJ (2011) Introduction to current and future protein therapeutics: a protein engineering perspective. Exp Cell Res 317:1261–1269

    Article  CAS  PubMed  Google Scholar 

  • Casal JI, Barderas R (2010) Identification of cancer autoantigens in serum. Mol Diagn Ther 14:149–154

    Article  CAS  PubMed  Google Scholar 

  • Chen CH, Dellamaggiore KR, Ouellette CP, Sedano CD (2008) Aptamer-based endocytosis of a lysosomal enzyme. Proc Natl Acad Sci USA 105:15908–15913

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chen K, Y-H Huang, J-L Chen (2013) Understanding and targeting cancer stem cells: therapeutic implications and challenges. Acta Pharmacol Sin 34:732–740

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chen H, Zucknick M, Werner S, Knebel P, Brenner H (2015) Head-to-head comparison and evaluation of 92 plasma protein biomarkers for early detection of colorectal cancer in a true screening setting. Clin Cancer Res 15:3318–3326

    Article  CAS  Google Scholar 

  • Ciardiello F, Tortora G (2008) EGFR antagonists in cancer treatment. New Engl J Med 358:1160–1174

    Article  CAS  PubMed  Google Scholar 

  • Citri A, Yarden Y (2006) EGF-ERBB signalling: towards the systems level. Nat Rev Mol Cell Biol 7:505–516

    Article  CAS  PubMed  Google Scholar 

  • Coghlin C, Murray GI (2013) Progress in the identification of plasma biomarkers of colorectal cancer. Proteomics 13:2227–2228

    Article  CAS  PubMed  Google Scholar 

  • De Wit M, Fijneman RJA, Verheul HMW, Meijer GA, Jimenez CR (2013) Proteomics in colorectal cancer translational research: biomarker discovery for clinical applications. Clin Biochem 46:466–479

    Article  PubMed  CAS  Google Scholar 

  • DeRycke MS, Gunawardena SR, Middha S, Asmann YW et al (2013) Identification of novel variants in colorectal cancer families by high-throughput exome sequencing. Cancer Epidemiol Prev Biomark 22:1239–1251

    Article  CAS  Google Scholar 

  • Dettmer K, Aronov PA, Hammock BD (2007) Mass spectrometry-based metabolomics. Mass Spectrom Rev 26:51–78

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dhar S, Kolishetti N, Lippard SJ, Farokhzad OC (2011) Targeted delivery of a cisplatin prodrug for safer and more effective prostate cancer therapy in vivo. Proc Natl Acad Sci USA 108:1850–1855

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Di Fiore F, Blanchard F, Charbonnier F, Le Pessot F (2007) Clinical relevance of KRAS mutation detection in metastatic colorectal cancer treated by Cetuximab plus chemotherapy. Br J Cancer 96:1166–1169

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Di Lena M, Porcelli F, Altomare DF (2016) Volatile organic compounds (VOC) as new biomarkers for colorectal cancer: a review. Colorectal Dis 18:654–663

    Article  PubMed  Google Scholar 

  • Distler J (2009) Quantification of methylated DNA by heavymethyl duplex PCR. In: Tost J (ed) DNA methylation: methods and protocols, 2nd edn. Humana Press, New York, pp 339–346

    Chapter  Google Scholar 

  • Dong SM, Traverso G, Johnson C, Geng L (2001) Detecting colorectal cancer in stool with the use of multiple genetic targets. J Natl Cancer Inst 93:858–865

    Article  CAS  PubMed  Google Scholar 

  • Dorudi S, Steele RJ, McArdle CS (2002) Surgery for colorectal cancer. Br Med Bull 64:101–118

    Article  PubMed  Google Scholar 

  • Down TA, Rakyan VK, Turner DJ, Flicek P et al (2008) A Bayesian deconvolution strategy for immunoprecipitation-based DNA methylome analysis. Nat Biotechnol 26:779–785

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dunn BK (2003) Hypomethylation: one side of a larger picture. Ann NY Acad Sci 983:28–42

    Article  CAS  PubMed  Google Scholar 

  • Dvorak HF (2000) VPF/VEGF and the angiogenic response. Semin Perinatol 24:75–78

    Article  CAS  PubMed  Google Scholar 

  • Eads CA, Danenberg KD, Kawakami K, Saltz LB (2000) MethyLight: a high-throughput assay to measure DNA methylation. Nucleic Acid Res 28:e32-00

    Article  Google Scholar 

  • Ecker DM, Jones SD, Levine HL (2015) The therapeutic monoclonal antibody market. Mabs 7:9–14

    Article  CAS  PubMed  Google Scholar 

  • Ellington AD, Szostak JW (1990) In vitro selection of RNA molecules that bind specific ligands. Nature 346:818–822

    Article  CAS  PubMed  Google Scholar 

  • Esteller M (2007) Cancer epigenomics: dNA methylomes and histone-modification maps. Nat Rev Genet 8:286–298

    Article  CAS  PubMed  Google Scholar 

  • Esteller M, Herman JG (2002) Cancer as an epigenetic disease: DNA methylation and chromatin alterations in human tumours. J Pathol 196:1–7

    Article  CAS  PubMed  Google Scholar 

  • Fanali C, Lucchetti D, Farina M, Corbi M et al (2014) Cancer stem cells in colorectal cancer from pathogenesis to therapy: controversies and perspectives. World J Gastroenterol 20:923–942

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Fearon ER, Vogelstein B (1990) A genetic model for colorectal tumorigenesis. Cell 61:759–767

    Article  CAS  PubMed  Google Scholar 

  • Ferrara N (2005) The role of VEGF in the regulation of physiological and pathological angiogenesis. Mech Angiogenesis 94:209–231

    Article  Google Scholar 

  • Flusberg BA, Webster DR, Lee JH, Travers KJ et al (2010) Direct detection of DNA methylation during single-molecule, real-time sequencing. Nat Methods 7:461–465

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Frank NY, Schatton T, Frank MH (2010) The therapeutic promise of the cancer stem cell concept. J Clin Investig 120:41–50

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Friedman M, Stahl S (2009) Engineered affinity proteins for tumour-targeting applications. Biotechnol Appl Biochem 53:1–29

    Article  CAS  PubMed  Google Scholar 

  • Gao X, Tang C, Shi W, Feng S et al (2015) Semaphorin-3F functions as a tumor suppressor in colorectal cancer due to regulation by DNA methylation. Int J Clin Exp Pathol 8:12766

    PubMed  PubMed Central  Google Scholar 

  • Gold P, Freedman SO (1965) Demonstration of tumor-specific antigenes in human colonic carcinomata by immunological tolerance and absorption techniques. J Exp Med 121:439–462

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Goyle S, Maraveyas A (2005) Chemotherapy for colorectal cancer. Dig Surg 22:401–414

    Article  CAS  PubMed  Google Scholar 

  • Grada A, Weinbrecht K (2013) Next-generation sequencing: methodology and application. J Invest Dermatol 133(8):e11

    Article  PubMed  CAS  Google Scholar 

  • Greenwald B (2015) A review of the American Cancer Society’s 2015 colorectal cancer screening recommendations. Gastroenterol Nurs 38:230–234

    Article  PubMed  Google Scholar 

  • Hagan S, Orr MCM, Doyle B (2013) Targeted therapies in colorectal cancer—an integrative view by PPPM. EPMA J 4:3–3

    Article  PubMed  PubMed Central  Google Scholar 

  • Haggblad Sahlberg S, Spiegelberg D, Lennartsson J, Nygren P et al (2012) The effect of a dimeric affibody molecule (ZEGFR:1907)2 targeting EGFR in combination with radiation in colon cancer cell lines. Int J Oncol 40:176–184

    PubMed  Google Scholar 

  • Harding KE, Robertson NP (2014) Applications of next-generation whole exome sequencing. J Neurol 261:1244

    Article  PubMed  Google Scholar 

  • He B, You L, Uematsu K, Xu Z et al (2004a) A monoclonal antibody against Wnt-1 induces apoptosis in human cancer cells. Neoplasia 6:7–14

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • He XC, Zhang J, Tong WG, Tawfik O et al (2004b) BMP signaling inhibits intestinal stem cell self-renewal through suppression of Wnt-beta-catenin signaling. Nat Genet 36:1117–1121

    Article  CAS  PubMed  Google Scholar 

  • Hemmerle T, Neri D (2014) The antibody-based targeted delivery of interleukin-4 and 12 to the tumor neovasculature eradicates tumors in three mouse models of cancer. Int J Cancer 134:467–477

    Article  PubMed  CAS  Google Scholar 

  • Hiraoka D, Yoshida W, Abe K, Wakeda H et al (2012) Development of a method to measure DNA methylation levels by using methyl CpG-binding protein and luciferase-fused zinc finger protein. Anal Chem 84:8259–8264

    Article  CAS  PubMed  Google Scholar 

  • Hoey T, Yen WC, Axelrod F, Basi J et al (2009) DLL4 blockade inhibits tumor growth and reduces tumor-initiating cell frequency. Cell Stem Cell 5:168–177

    Article  CAS  PubMed  Google Scholar 

  • Holst S, Stavenhagen K, Balog CI, Koeleman CA et al (2013) Investigations on aberrant glycosylation of glycosphingolipids in colorectal cancer tissues using liquid chromatography and matrix-assisted laser desorption time-of-flight mass spectrometry (MALDI-TOF-MS). Mol Cell Proteomics 12:3081–3093

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hong I-S, Jang G-B, Lee H-Y, Nam J-S (2015) Targeting cancer stem cells by using the nanoparticles. Int J Nanomed 10:251–260

    CAS  Google Scholar 

  • Hosse RJ, Rothe A, Power BE (2006) A new generation of protein display scaffolds for molecular recognition. Protein Sci 15:14–27

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Huebert DJ, Kamal M, O’Donovan A, Bernstein BE (2006) Genome-wide analysis of histone modifications by ChIP-on-chip. Methods 40:365–369

    Article  CAS  PubMed  Google Scholar 

  • Hurwitz H, Fehrenbacher L, Novotny W, Cartwright T et al (2004) Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. New Engl J Med 350:2335–2342

    Article  CAS  PubMed  Google Scholar 

  • Iqbal S, Lenz HJ (2004) Integration of novel agents in the treatment of colorectal cancer. Cancer Chemoth Pharm 54(Suppl 1):S32–S39

    CAS  Google Scholar 

  • Jalalian SH, Taghdisi SM, Shahidi Hamedani N, Kalat SA et al (2013) Epirubicin loaded super paramagnetic iron oxide nanoparticle-aptamer bioconjugate for combined colon cancer therapy and imaging in vivo. Eur J Pharm Sci 50:191–197

    Article  CAS  PubMed  Google Scholar 

  • Jimenez CR, Knol JC, Meijer GA, Fijneman RJA (2010) Proteomics of colorectal cancer: overview of discovery studies and identification of commonly identified cancer-associated proteins and candidate CRC serum markers. J Proteomics 73:1873–1895

    Article  CAS  PubMed  Google Scholar 

  • Jiménez B, Mirnezami R, Kinross J, Cloarec O et al (2013) 1H HR-MAS NMR spectroscopy of tumor-induced local metabolic “field-effects” enables colorectal cancer staging and prognostication. J Proteome Res 12:959–968

    Article  PubMed  CAS  Google Scholar 

  • Jonker DJ, O’Callaghan CJ, Karapetis CS, Zalcberg JR et al (2007) Cetuximab for the treatment of colorectal cancer. New Engl J Med 357:2040–2048

    Article  CAS  PubMed  Google Scholar 

  • Kaleko M, Rutter WJ, Miller AD (1990) Overexpression of the human insulinlike growth factor I receptor promotes ligand-dependent neoplastic transformation. Mol Cell Biol 10:464–473

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Karapetis CS, Khambata-Ford S, Jonker DJ, O’Callaghan CJ et al (2008) K-ras mutations and benefit from cetuximab in advanced colorectal cancer. New Engl J Med 359:1757–1765

    Article  CAS  PubMed  Google Scholar 

  • Kawashima H (2014) Radioimmunotherapy: a specific treatment protocol for cancer by cytotoxic radioisotopes conjugated to antibodies. Sci World J 2014:10

    Article  CAS  Google Scholar 

  • Keefe DM, Elting LS, Nguyen HT, Grunberg SM et al (2014) Risk and outcomes of chemotherapy-induced diarrhea (CID) among patients with colorectal cancer receiving multi-cycle chemotherapy. Cancer Chemoth Pharm 74:675–680

    Article  CAS  Google Scholar 

  • Klier U, Maletzki C, Gottmann N, Kreikemeyer B et al (2011) Avitalized bacteria mediate tumor growth control via activation of innate immunity. Cell Immunol 269:120–127

    Article  CAS  PubMed  Google Scholar 

  • Kobayashi H, Mochizuki H, Morita T, Kotake K et al (2011) Characteristics of recurrence after curative resection for T1 colorectal cancer: Japanese multicenter study. J Gastroenterol 46:203–211

    Article  PubMed  Google Scholar 

  • Korshunova Y, Maloney RK, Lakey N, Citek RW et al (2008) Massively parallel bisulphite pyrosequencing reveals the molecular complexity of breast cancer-associated cytosine-methylation patterns obtained from tissue and serum DNA. Genome Res 18:19–29

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kumar M, Sarin SK (2009) Biomarkers of diseases in medicine. Curr Trends Sci 70:403–417

    Google Scholar 

  • Kurdyukov S, Bullock M (2016) DNA methylation analysis: choosing the right method. Biology 5:3

    Article  PubMed Central  Google Scholar 

  • Kwak H, Hwang I, Kim JH, Kim MY et al (2009) Modulation of transcription by the peroxisome proliferator-activated receptor delta–binding RNA aptamer in colon cancer cells. Mol Cancer Ther 8:2664–2673

    Article  CAS  PubMed  Google Scholar 

  • Kwak PB, Iwasaki S, Tomari Y (2010) The microRNA pathway and cancer. Cancer Sci 101:2309–2315

    Article  CAS  PubMed  Google Scholar 

  • Langan RC, Mullinax JE, Raiji MT, Upham T et al (2013) Colorectal cancer biomarkers and the potential role of cancer stem cells. J Cancer 4:241–250

    Article  PubMed  PubMed Central  Google Scholar 

  • Lee HK, Choi YS, Park YA, Jeong S (2006) Modulation of oncogenic transcription and alternative splicing by beta-catenin and an RNA aptamer in colon cancer cells. Cancer Res 66:10560–10566

    Article  CAS  PubMed  Google Scholar 

  • Lee YJ, Han SR, Kim NY, Lee SH et al (2012) An RNA aptamer that binds carcinoembryonic antigen inhibits hepatic metastasis of colon cancer cells in mice. Gastroenterology 143:155–165

    Article  CAS  PubMed  Google Scholar 

  • Leichtle AB, Nuoffer JM, Ceglarek U, Kase J et al (2012) Serum amino acid profiles and their alterations in colorectal cancer. Metabolomics 8:643–653

    Article  CAS  PubMed  Google Scholar 

  • Li E, Bestor TH, Jaenisch R (1992) Targeted mutation of the DNA methyltransferase gene results in embryonic lethality. Cell 69:915–926

    Article  CAS  PubMed  Google Scholar 

  • Li E, Beard C, Jaenisch R (1993) Role for DNA methylation in genomic imprinting. Nature 366:362–365

    Article  CAS  PubMed  Google Scholar 

  • Li J, Tan S, Chen X, Zhang CY, Zhang Y (2011) Peptide aptamers with biological and therapeutic applications. Curr Med Chem 18:4215–4222

    Article  CAS  PubMed  Google Scholar 

  • Li X, Zhao Q, Qiu L (2013) Smart ligand: aptamer-mediated targeted delivery of chemotherapeutic drugs and siRNA for cancer therapy. J Contr Release 171:152–162

    Article  CAS  Google Scholar 

  • Li L, Xiang D, Shigdar S, Yang W et al (2014) Epithelial cell adhesion molecule aptamer functionalized PLGA-lecithin-curcumin-PEG nanoparticles for targeted drug delivery to human colorectal adenocarcinoma cells. Int J Nanomed 9:1083–1096

    Article  CAS  Google Scholar 

  • Linardou H, Dahabreh IJ, Kanaloupiti D, Siannis F et al (2008) Assessment of somatic k-RAS mutations as a mechanism associated with resistance to EGFR-targeted agents: a systematic review and meta-analysis of studies in advanced non-small-cell lung cancer and metastatic colorectal cancer. Lancet Oncol 9:962–972

    Article  CAS  PubMed  Google Scholar 

  • Liu C-G, Calin GA, Volinia S, Croce CM (2008) MicroRNA expression profiling using microarrays. Nat Protoc 3:563–578

    Article  CAS  PubMed  Google Scholar 

  • Löfblom J, Frejd FY, Ståhl S (2011) Non-immunoglobulin based protein scaffolds. Curr Opin Biotechnol 22:843–848

    Article  PubMed  CAS  Google Scholar 

  • Ma Y, Zhang H, Liu F, Wu Z et al (2015) Highly sensitive detection of DNA methylation levels by using a quantum dot-based FRET method. Nanoscale 7:17547–17555

    Article  CAS  PubMed  Google Scholar 

  • Manna SK, Tanaka N, Krausz KW, Haznadar M et al (2014) Biomarkers of coordinate metabolic reprogramming in colorectal tumors in mice and humans. Gastroenterology 146:1313–1324

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mao C, Yang ZY, Hu XF, Chen Q, Tang JL (2012) PIK3CA exon 20 mutations as a potential biomarker for resistance to anti-EGFR monoclonal antibodies in KRAS wild-type metastatic colorectal cancer: a systematic review and meta-analysis. Ann Oncol 23:1518–1525

    Article  CAS  PubMed  Google Scholar 

  • Migheli F, Migliore L (2012) Epigenetics of colorectal cancer. Clin Genet 81:312–318

    Article  CAS  PubMed  Google Scholar 

  • Mokarram P, Zamani M, Kavousipour S, Naghibalhossaini F et al (2013) Different patterns of DNA methylation of the two distinct O6-methylguanine-DNA methyltransferase (O6-MGMT) promoter regions in colorectal cancer. Mol Biol Rep 40:3851–3857

    Article  CAS  PubMed  Google Scholar 

  • Mokarram P, Zare N, Jafari H, Kavousipour S et al (2015) The methylation status of MGMT and SFRP2 genes in Iranian patients with polyps. Thrita 4:e28601

    Article  Google Scholar 

  • Muller D, Kontermann RE (2007) Recombinant bispecific antibodies for cellular cancer immunotherapy. Curr Opin Mol Ther 9:319–326

    PubMed  Google Scholar 

  • Naghibalhossaini F, Hosseini HM, Mokarram P, Zamani M (2011) High frequency of genes’ promoter methylation, but lack of BRAF V600E mutation among Iranian colorectal cancer patients. Pathol Oncol Res 17:819–825

    Article  CAS  PubMed  Google Scholar 

  • Newton KF, Newman W, Hill J (2012) Review of biomarkers in colorectal cancer. Colorectal Dis 14:3–17

    Article  CAS  PubMed  Google Scholar 

  • Ng EK, Chong WW, Lam EK, Shin VY et al (2009) Differential expression of microRNAs in plasma of colorectal cancer patients: a potential marker for colorectal cancer screening. Gut 58:1375–1381

    Article  CAS  PubMed  Google Scholar 

  • Ni Y, Xie G, Jia W (2014) Metabonomics of human colorectal cancer: new approaches for early diagnosis and biomarker discovery. J Proteome Res 13:3857–3870

    Article  CAS  PubMed  Google Scholar 

  • Nishiumi S, Kobayashi T, Ikeda A, Yoshie T et al (2012) A novel serum metabolomics-based diagnostic approach for colorectal cancer. PLoS ONE 7:e40459

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Noguchi T, Ritter G, Nishikawa H (2013) Antibody-based therapy in colorectal cancer. Immunotherapy 5:533–545

    Article  CAS  PubMed  Google Scholar 

  • Nygren AO, Ameziane N, Duarte HM, Vijzelaar RN et al (2005) Methylation-specific MLPA (MS-MLPA): simultaneous detection of CpG methylation and copy number changes of up to 40 sequences. Nucleic Acid Res 33:e128–e128

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Oberst MD, Fuhrmann S, Mulgrew K, Amann M et al (2014) CEA/CD3 bispecific antibody MEDI-565/AMG 211 activation of T cells and subsequent killing of human tumors is independent of mutations commonly found in colorectal adenocarcinomas. Mabs 6:1571–1584

    Article  PubMed  PubMed Central  Google Scholar 

  • O’Brien CA, Pollett A, Gallinger S, Dick JE (2007) A human colon cancer cell capable of initiating tumour growth in immunodeficient mice. Nature 445:106–110

    Article  PubMed  CAS  Google Scholar 

  • O’Connell MJ (2004) Current status of adjuvant therapy for colorectal cancer. Oncology 18:751–755

    PubMed  Google Scholar 

  • Ohuchi S (2012) Cell-SELEX technology. BioRes Open Access 1:265–272

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Okugawa Y, Grady WM, Goel A (2015) Epigenetic alterations in colorectal cancer: emerging biomarkers. Gastroenterology 149:1204–1225

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ouban A, Muraca P, Yeatman T, Coppola D (2003) Expression and distribution of insulin-like growth factor-1 receptor in human carcinomas. Hum Pathol 34:803–808

    Article  CAS  PubMed  Google Scholar 

  • Parikh NI, Vasan RS (2007) Assessing the clinical utility of biomarkers in medicine. Biomark Med 1:419–436

    Article  CAS  PubMed  Google Scholar 

  • Park HC, Choi DH (2010) Radiation therapy for colorectal cancer. J Korean Med Assoc 53:592–602

    Article  Google Scholar 

  • Pasetto LM, Bortolami A, Falci C, Sinigaglia G, Monfardini S (2006) Recent progress in target therapy in colorectal cancer. Anticancer Res 26:3973–3981

    CAS  PubMed  Google Scholar 

  • Patel S, Ahmed S (2015) Emerging field of metabolomics: big promise for cancer biomarker identification and drug discovery. J Pharm Biomed 107:63–74

    Article  CAS  Google Scholar 

  • Patti GJ, Yanes O, Siuzdak G (2012) Innovation: metabolomics: the apogee of the omics trilogy. Nat Rev Mol Cell Biol 13:263–269

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Paun O, Schönswetter P (2012) Plant DNA fingerprinting and barcoding: methods and protocols. In: Sucher NJ, Hennell JR, Carles MC (eds) Amplified fragment length polymorphism: an invaluable fingerprinting technique for genomic, transcriptomic, and epigenetic studies. Humana Press, New York, pp 75–87

    Google Scholar 

  • Phua LC, Chue XP, Koh PK, Cheah PY et al (2014) Non-invasive fecal metabonomic detection of colorectal cancer. Cancer Biol Ther 15:389–397

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pino MS, Chung DC (2010) The chromosomal instability pathway in colon cancer. Gastroenterology 138:2059–2072

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pinto D, Gregorieff A, Begthel H, Clevers H (2003) Canonical Wnt signals are essential for homeostasis of the intestinal epithelium. Gene Dev 17:1709–1713

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Poh W, Wong W, Ong H, Aung MO et al (2012) Klotho-beta overexpression as a novel target for suppressing proliferation and fibroblast growth factor receptor-4 signaling in hepatocellular carcinoma. Mol Cancer 11:1–10

    Article  CAS  Google Scholar 

  • Rauch TA, Pfeifer GP (2009) The MIRA method for DNA methylation analysis DNA methylation: methods and protocols. Method Mol Biol 507:65–75

    Article  CAS  Google Scholar 

  • Reidy DL, Vakiani E, Fakih MG, Saif MW et al (2010) Randomized, phase II study of the insulin-like growth factor-1 receptor inhibitor IMC-A12, with or without cetuximab, in patients with cetuximab- or panitumumab-refractory metastatic colorectal cancer. J Clin Oncol 28:4240–4246

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Reinmuth N, Liu W, Fan F, Jung YD et al (2002) Blockade of insulin-like growth factor I receptor function inhibits growth and angiogenesis of colon cancer. Clin Cancer Res 8:3259–3269

    CAS  PubMed  Google Scholar 

  • Ricci-Vitiani L, Lombardi DG, Pilozzi E, Biffoni M et al (2007) Identification and expansion of human colon-cancer-initiating cells. Nature 445:111–115

    Article  CAS  PubMed  Google Scholar 

  • Robles AI, Traverso G, Zhang M, Roberts NJ et al (2016) Whole-exome sequencing analyses of inflammatory bowel disease-associated colorectal cancers. Gastroenterology 150:931–943

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rothe A, Jachimowicz RD, Borchmann S, Madlener M et al (2014) The bispecific immunoligand ULBP2-aCEA redirects natural killer cells to tumor cells and reveals potent anti-tumor activity against colon carcinoma. Int J Cancer 134:2829–2840

    Article  CAS  PubMed  Google Scholar 

  • Sachdev D, Singh R, Fujita-Yamaguchi Y, Yee D (2006) Down-regulation of insulin receptor by antibodies against the type I insulin-like growth factor receptor: implications for anti-insulin-like growth factor therapy in breast cancer. Cancer Res 66:2391–2402

    Article  CAS  PubMed  Google Scholar 

  • Sagiv E, Memeo L, Karin A, Kazanov D et al (2006) CD24 is a new oncogene, early at the multistep process of colorectal cancer carcinogenesis. Gastroenterology 131:630–639

    Article  CAS  PubMed  Google Scholar 

  • Saltz L, Clarke S, Diaz-Rubio E, Scheithauer WB et al (2008) Bevacizumab in combination with oxaliplatin-based chemotherapy as first-line therapy in metastatic colorectal cancer: a randomized phase III study. J Clin Oncol 26:2013–2019

    Article  CAS  PubMed  Google Scholar 

  • Sato Y, Matsusaka S, Suenaga M, Shinozaki E et al (2015) Cetuximab could be more effective without prior bevacizumab treatment in metastatic colorectal cancer patients. Oncol Target Ther 8:3329–3336

    Article  Google Scholar 

  • Scanlan MJ, Chen YT, Williamson B, Gure AO et al (1998) Characterization of human colon cancer antigens recognized by autologous antibodies. Int J Cancer 76:652–658

    Article  CAS  PubMed  Google Scholar 

  • Schetter AJ, Leung SY, Sohn JJ, Zanetti KA et al (2008) MicroRNA expression profiles associated with prognosis and therapeutic outcome in colon adenocarcinoma. J Am Med Assoc 299:425–436

    CAS  Google Scholar 

  • Schmittgen TD, Lee EJ, Jiang J, Sarkar A et al (2008) Real-time PCR quantification of precursor and mature microRNA. Methods 44:31–38

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schmohl JU, Gleason MK, Dougherty PR, Miller JS, Vallera DA (2015) Heterodimeric bispecific single chain variable fragments (scFv) killer engagers (BiKEs) enhance NK-cell activity against CD133 + colorectal cancer cells. Target Oncol 11:353–361

    Article  Google Scholar 

  • Schnekenburger M, Diederich M (2012) Epigenetics offer new horizons for colorectal cancer prevention. Curr Colorectal Cancer Rep 8:66–81

    Article  PubMed  PubMed Central  Google Scholar 

  • Schreuders EH, Grobbee EJ, Spaander MC, Kuipers EJ (2016) Advances in fecal tests for colorectal cancer screening. Curr Treat Option Gastroenterol 14:152–162

    Article  Google Scholar 

  • Shanmuganathan R, Basheer NB, Amirthalingam L, Muthukumar H et al (2013) Conventional and nanotechniques for DNA methylation profiling. J Mol Diagn 15:17–26

    Article  CAS  PubMed  Google Scholar 

  • Shim J, Kim Y, Humphreys GI, Nardulli AM et al (2015) Nanopore-based assay for detection of methylation in double-stranded DNA fragments. ACS Nano 9:290–300

    Article  CAS  PubMed  Google Scholar 

  • Siegel R, Naishadham D, Jemal A (2013) Cancer statistics, 2013. CA Cancer J Clin 63:11–30

    Article  PubMed  Google Scholar 

  • Singer-Sam J, Riggs AD (1993) X chromosome inactivation and DNA methylation. In: Jost J, Saluz H (eds) DNA methylation, 1st edn. Birkhäuser, Basel, pp 358–384

    Chapter  Google Scholar 

  • Smith ZD, Gu H, Bock C, Gnirke A et al (2009) High-throughput bisulfite sequencing in mammalian genomes. Methods 48:226–232

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sotelo MJ, García-Paredes B, Aguado C, Sastre J, Díaz-Rubio E (2014) Role of cetuximab in first-line treatment of metastatic colorectal cancer. World J Gastroenterol 20:4208–4219

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sundström M, Edlund K, Lindell M, Glimelius B et al (2010) KRAS analysis in colorectal carcinoma: analytical aspects of pyrosequencing and allele-specific PCR in clinical practice. BMC Cancer 10:660

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Surinova S, Choi M, Tao S, Schüffler PJ et al (2015) Prediction of colorectal cancer diagnosis based on circulating plasma proteins. EMBO Mol Med 7:1166–1178

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Szmida E, Karpiński P, Leszczynski P, Sedziak T et al (2015) Aberrant methylation of ERBB pathway genes in sporadic colorectal cancer. J Appl Genet 56:185–192

    Article  CAS  PubMed  Google Scholar 

  • Tagore K, Lawson MJ, Yucaitis JA, Gage R et al (2003) Sensitivity and specificity of a stool DNA multitarget assay panel for the detection of advanced colorectal neoplasia. Clin Colorectal Cancer 3:47–53

    Article  CAS  PubMed  Google Scholar 

  • Talelli M, Oliveira S, Rijcken CJ, Pieters EH et al (2013) Intrinsically active nanobody-modified polymeric micelles for tumor-targeted combination therapy. Biomaterials 34:1255–1260

    Article  CAS  PubMed  Google Scholar 

  • Tan HT, Low J, Lim SG, Chung M (2009) Serum autoantibodies as biomarkers for early cancer detection. FEBS J 276:6880–6904

    Article  CAS  PubMed  Google Scholar 

  • Tan B, Qiu Y, Zou X, Chen T et al (2013) Metabonomics identifies serum metabolite markers of colorectal cancer. J Proteome Res 12:3000–3009

    Article  CAS  PubMed  Google Scholar 

  • Tanaka T, Tanaka M, Tanaka T, Ishigamori R (2010) Biomarkers for colorectal cancer. Int J Mol Sci 11:3209–3225

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tome-Amat J, Menendez-Mendez A, Garcia-Ortega L, Batt CA et al (2012) Production and characterization of scFvA33T1, an immunoRNase targeting colon cancer cells. FEBS J 279:3022–3032

    Article  CAS  PubMed  Google Scholar 

  • Tomé-Amat J, Olombrada M, Ruiz-de-la-Herrán J, Pérez-Gómez E et al (2015) Efficient in vivo antitumor effect of an immunotoxin based on ribotoxin α-sarcin in nude mice bearing human colorectal cancer xenografts. SpringerPlus 4:168

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Tost J, Gut IG (2007) DNA methylation analysis by pyrosequencing. Nat Protoc 2:2265–2275

    Article  CAS  PubMed  Google Scholar 

  • Tuerk C, Gold L (1990) Systematic evolution of ligands by exponential enrichment: rNA ligands to bacteriophage T4 DNA polymerase. Science 249:505–510

    Article  CAS  PubMed  Google Scholar 

  • Ulrich H, Trujillo CA, Nery AA, Alves JM et al (2006) DNA and RNA aptamers: from tools for basic research towards therapeutic applications. Comb Chem High Throughput Screen 9:619–632

    Article  CAS  PubMed  Google Scholar 

  • Vakili B, Mokarram P (2016) DNA-directed methylation analysis methodology. J Adv Med Sci Appl Technol 2:220–223

    Google Scholar 

  • Vallera DA, Zhang B, Gleason MK, Oh S et al (2013) Heterodimeric bispecific single-chain variable-fragment antibodies against EpCAM and CD16 induce effective antibody-dependent cellular cytotoxicity against human carcinoma cells. Cancer Biother Radiopharm 28:274–282

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Van Cutsem E, Kohne CH, Hitre E, Zaluski J et al (2009) Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer. New Engl J Med 360:1408–1417

    Article  PubMed  Google Scholar 

  • Van de Broek B, Devoogdt N, D’Hollander A, Gijs HL et al (2011) Specific cell targeting with nanobody conjugated branched gold nanoparticles for photothermal therapy. ACS Nano 5:4319–4328

    Article  PubMed  CAS  Google Scholar 

  • Van der Meel R, Oliveira S, Altintas I, Haselberg R et al (2012) Tumor-targeted Nanobullets: anti-EGFR nanobody-liposomes loaded with anti-IGF-1R kinase inhibitor for cancer treatment. J Control Release 159:281–289

    Article  PubMed  CAS  Google Scholar 

  • Vanneman M, Dranoff G (2012) Combining immunotherapy and targeted therapies in cancer treatment. Nat Rev Cancer 12:237–251

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vazquez-Lombardi R, Phan TG, Zimmermann C, Lowe D et al (2015) Challenges and opportunities for non-antibody scaffold drugs. Drug Discov Today 20:1271–1283

    Article  CAS  PubMed  Google Scholar 

  • Veenstra TD, Conrads TP, Hood BL, Avellino AM et al (2005) Biomarkers: mining the biofluid proteome. Mol Cell Proteome 4:409–418

    Article  CAS  Google Scholar 

  • Vermeulen L, Todaro M, Sousa Mello F, Sprick MR et al (2008) Single-cell cloning of colon cancer stem cells reveals a multi-lineage differentiation capacity. Proc Natl Acad Sci USA 105:13427–13432

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Waldron NN, Barsky SH, Dougherty PR, Vallera DA (2014) A bispecific EpCAM/CD133-targeted toxin is effective against carcinoma. Target Oncol 9:239–249

    Article  PubMed  Google Scholar 

  • Wang R, Zhu G, Mei L, Xie Y et al (2014) Automated modular synthesis of aptamer–drug conjugates for targeted drug delivery. J Am Chem Soc 136:2731–2734

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wiela-Hojenska A, Kowalska T, Filipczyk-Cisarz E, Lapinski L et al (2015) Evaluation of the toxicity of anticancer chemotherapy in patients with colon cancer. Adv Clin Exp Med 24:103–111

    Article  PubMed  Google Scholar 

  • Wu X, Chen J, Wu M, Zhao JX (2015) Aptamers: active targeting ligands for cancer diagnosis and therapy. Theranostics 5:322–344

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Wurch T, Lowe P, Caussanel V, Bes C et al (2008) Development of novel protein scaffolds as alternatives to whole antibodies for imaging and therapy: status on discovery research and clinical validation. Curr Pharm Biotechnol 9:502–509

    Article  CAS  PubMed  Google Scholar 

  • Xia J, Guo X, Deng K (2014) MicroRNAs: key regulators of oncogenesis. In: Babashah S (ed) Epigenetics, MicroRNAs and human cancer. Springer, Berlin, pp 29–57

    Google Scholar 

  • Xiang D, Zheng C, Zhou SF, Qiao S et al (2015) Superior performance of aptamer in tumor penetration over antibody: implication of aptamer-based theranostics in solid tumors. Theranostics 5:1083–1097

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xue Y, Ankala A, Wilcox WR, Hegde MR (2014) Solving the molecular diagnostic testing conundrum for Mendelian disorders in the era of next-generation sequencing: single-gene, gene panel, or exome/genome sequencing. Genet Med 17:444–451

    Article  PubMed  CAS  Google Scholar 

  • Yin S, Li J, Hu C, Chen X et al (2007) CD133 positive hepatocellular carcinoma cells possess high capacity for tumorigenicity. Int J Cancer 120:1444–1450

    Article  CAS  PubMed  Google Scholar 

  • Yu M, Jambhrunkar S, Thorn P, Chen J et al (2013) Hyaluronic acid modified mesoporous silica nanoparticles for targeted drug delivery to CD44-overexpressing cancer cells. Nanoscale 5:178–183

    Article  CAS  PubMed  Google Scholar 

  • Zeschnigk M, Böhringer S, Price EA, Onadim Z et al (2004) A novel real-time PCR assay for quantitative analysis of methylated alleles (QAMA): analysis of the retinoblastoma locus. Nucleic Acid Res 32:e125

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Zhang L, Radovic-Moreno AF, Alexis F, Gu F et al (2007) Co-delivery of hydrophobic and hydrophilic drugs from nanoparticle-aptamer bioconjugates. Chem Med Chem 2:1268–1271

    Article  CAS  PubMed  Google Scholar 

  • Zhao L, Yang Y, Zhou P, Ma H et al (2015) Targeting CD133high colorectal cancer cells in vitro and in vivo with an asymmetric bispecific antibody. J Immunother 38:217–228

    Article  CAS  PubMed  Google Scholar 

  • Zhou W, Liotta LA, Petricoin EF (2015) Cancer metabolism and mass spectrometry-based proteomics. Cancer Lett 356:176–183

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgement

The authors would like to thank the Research Consultation Center (RCC) of Shiraz University of Medical Sciences for their invaluable assistance in editing this article. Especial thanks to Mr. Argasi, Mr. Rezaie and Ms. Masoumi for his contribution and insight in editing this article.

Disclosure

Authors declare they have no financial disclosure.

Author information

Authors and Affiliations

  1. Department of Biotechnology, School of Advanced Medical Science and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran

    Soudabeh Kavousipour & Bahareh Vakili

  2. Department of Biochemistry, School of Medicine, Shiraz University of Medical Sciences, P.O Box 1167, Shiraz, Iran

    Fathemeh Khademi & Pooneh Mokarram

  3. Colorectal Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

    Mozhdeh Zamani & Pooneh Mokarram

  4. School of Medicine, Nemazee Hospital, Gastroenterohepatology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

    Pooneh Mokarram

Authors
  1. Soudabeh Kavousipour
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Fathemeh Khademi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mozhdeh Zamani
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Bahareh Vakili
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Pooneh Mokarram
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Pooneh Mokarram.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kavousipour, S., Khademi, F., Zamani, M. et al. Novel biotechnology approaches in colorectal cancer diagnosis and therapy. Biotechnol Lett 39, 785–803 (2017). https://doi.org/10.1007/s10529-017-2303-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10529-017-2303-8

Keywords

Search

Navigation