title: Lung cancer screening beyond low-dose computed tomography: the role of novel biomarkers.
abstract: Lung cancer is the most common and lethal malignancy in the world. The landmark National lung screening trial (NLST) showed a 20% relative reduction in mortality in high-risk individuals with screening low-dose computed tomography. However, the poor specificity and low prevalence of lung cancer in the NLST provide major limitations to its widespread use. Furthermore, a lung nodule on CT scan requires a nuanced and individualized approach towards management. In this regard, advances in high through-put technology (molecular diagnostics, multi-gene chips, proteomics, and bronchoscopic techniques) have led to discovery of lung cancer biomarkers that have shown potential to complement the current screening standards. Early detection of lung cancer can be achieved by analysis of biomarkers from tissue samples within the respiratory tract such as sputum, saliva, nasal/bronchial airway epithelial cells and exhaled breath condensate or through peripheral biofluids such as blood, serum and urine. Autofluorescence bronchoscopy has been employed in research setting to identify pre-invasive lesions not identified on CT scan. Although these modalities are not yet commercially available in clinic setting, they will be available in the near future and clinicians who care for patients with lung cancer should be aware. In this review, we present up-to-date state of biomarker development, discuss their clinical relevance and predict their future role in lung cancer management.
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Sidney Kimmel Medical College at Thomas Jefferson University and Hospital, 834 Walnut St, Suite 650, Philadelphia, PA, 19107, USA.
authors.forename: Naveed
authors.initials: N
authors.lastname: Hasan
authors.forename: Rohit
authors.initials: R
authors.lastname: Kumar
authors.forename: Mani S
authors.initials: MS
authors.lastname: Kavuru
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D055088:Early Detection of Cancer / Q000379:methods*; D006801:Humans; D008168:Lung / Q000000981:diagnostic imaging* / Q000378:metabolism* / Q000473:pathology; D008175:Lung Neoplasms / Q000000981:diagnostic imaging* / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D011237:Predictive Value of Tests; D011379:Prognosis; D011829:Radiation Dosage; D014057:Tomography, X-Ray Computed
chemical_list: D014408:Biomarkers, Tumor
references.citation: Cancer Epidemiol Biomarkers Prev. 2012 May;21(5):786-92
references.pmid: 22374995
references.citation: Cancer Res. 2009 Aug 15;69(16):6694-703
references.pmid: 19679554
references.citation: JAMA. 2011 Nov 2;306(17):1865-73
references.pmid: 22031728
references.citation: Clin Cancer Res. 2005 Jan 15;11(2 Pt 1):537-43
references.pmid: 15701838
references.citation: Nat Med. 2007 Mar;13(3):361-6
references.pmid: 17334370
references.citation: Physiol Genomics. 2010 Mar 3;41(1):1-8
references.pmid: 19952278
references.citation: Cancer Epidemiol Biomarkers Prev. 2003 Feb;12(2):136-43
references.pmid: 12582023
references.citation: Integr Cancer Ther. 2006 Mar;5(1):30-9
references.pmid: 16484712
references.citation: Br J Cancer. 2008 Jan 29;98(2):270-6
references.pmid: 18087271
references.citation: N Engl J Med. 2011 Aug 4;365(5):395-409
references.pmid: 21714641
references.citation: Cancer Prev Res (Phila). 2011 Oct;4(10):1599-608
references.pmid: 21742797
references.citation: EMBO Mol Med. 2011 Aug;3(8):495-503
references.pmid: 21744498
references.citation: Thorax. 2007 Apr;62(4):335-40
references.pmid: 17101735
references.citation: J Thorac Oncol. 2010 Jun;5(6):778-85
references.pmid: 20421821
references.citation: Nat Rev Genet. 2005 Aug;6(8):597-610
references.pmid: 16136652
references.citation: J Thorac Oncol. 2011 Oct;6(10):1632-8
references.pmid: 21694641
references.citation: J Thorac Oncol. 2007 Oct;2(10):893-901
references.pmid: 17909350
references.citation: Clin Cancer Res. 2011 May 15;17(10):3360-7
references.pmid: 21558400
references.citation: Chest. 1999 Mar;115(3):720-4
references.pmid: 10084482
references.citation: Tumour Biol. 2012 Oct;33(5):1319-26
references.pmid: 22492236
references.citation: J Thorac Cardiovasc Surg. 1993 Jun;105(6):1035-40
references.pmid: 8501931
references.citation: Am J Respir Crit Care Med. 2005 Jun 1;171(11):1286-91
references.pmid: 15750044
references.citation: Eur Respir J. 2012 Mar;39(3):669-76
references.pmid: 21852337
references.citation: Clin Cancer Res. 2000 May;6(5):1611-2
references.pmid: 10815876
references.citation: BMC Cancer. 2011 Aug 24;11:374
references.pmid: 21864403
references.citation: J Natl Cancer Inst. 2008 Nov 5;100(21):1552-6
references.pmid: 18957677
references.citation: J Natl Cancer Inst. 2011 Jul 6;103(13):1058-68
references.pmid: 21606442
references.citation: J Natl Cancer Inst. 2003 Mar 19;95(6):470-8
references.pmid: 12644540
references.citation: Eur Respir J. 2009 Feb;33(2):352-9
references.pmid: 19010987
references.citation: Nature. 2007 Dec 20;450(7173):1235-9
references.pmid: 18097410
references.citation: Cancer Prev Res (Phila). 2012 Aug;5(8):992-1006
references.pmid: 22689914
references.citation: Int J Cancer. 2012 Apr 1;130(7):1620-8
references.pmid: 21557218
references.citation: J Natl Cancer Inst. 2007 May 2;99(9):715-26
references.pmid: 17470739
references.citation: Cancer Biomark. 2007;3(2):95-109
references.pmid: 17522431
references.citation: Cancer Prev Res (Phila). 2008 Jun;1(1):56-64
references.pmid: 19138936
references.citation: Respir Med. 2013 Jun;107(6):911-8
references.pmid: 23507584
references.citation: J Thorac Oncol. 2009 Jan;4(1):30-6
references.pmid: 19096303
references.citation: Cancer Res. 2011 Apr 15;71(8):3009-17
references.pmid: 21487035
references.citation: Ann Oncol. 2011 Feb;22(2):383-9
references.pmid: 20675559
references.citation: Am J Respir Crit Care Med. 2001 Nov 1;164(9):1688-93
references.pmid: 11719311
references.citation: Respir Res. 2012 Dec 21;13:117
references.pmid: 23259710
references.citation: J Clin Oncol. 2007 Dec 10;25(35):5578-83
references.pmid: 18065730
references.citation: J Thorac Dis. 2013 Oct;5 Suppl 5:S540-50
references.pmid: 24163746
references.citation: Clin Cancer Res. 1996 Oct;2(10):1767-75
references.pmid: 9816128
references.citation: Clin Cancer Res. 2011 Jul 1;17(13):4494-503
references.pmid: 21610147
references.citation: Lung Cancer. 2011 Aug;73(2):183-8
references.pmid: 21237526
references.citation: Nat Med. 2014 May;20(5):548-54
references.pmid: 24705333
references.citation: Chest. 1997 Jun;111(6):1710-7
references.pmid: 9187198
references.citation: Lung Cancer. 2014 Jan;83(1):51-5
references.pmid: 24268382
references.citation: Cancer Res. 1999 Jan 1;59(1):67-70
references.pmid: 9892187
references.citation: Proc Natl Acad Sci U S A. 2004 Jul 6;101(27):10143-8
references.pmid: 15210990
references.citation: J Med Screen. 2012 Sep;19(3):154-6
references.pmid: 23060474
references.citation: J Clin Oncol. 2003 Nov 1;21(21):3902-8
references.pmid: 14507943
references.citation: Mayo Clin Proc. 1993 Jun;68(6):603-11
references.pmid: 8388526
references.citation: Proc Natl Acad Sci U S A. 2011 Mar 1;108(9):3713-8
references.pmid: 21300873
references.citation: Cancer. 1953 Sep;6(5):963-8
references.pmid: 13094644
references.citation: BMC Genomics. 2008 May 30;9:259
references.pmid: 18513428
references.citation: Nature. 2005 Jun 9;435(7043):834-8
references.pmid: 15944708
references.citation: BMC Cancer. 2010 Nov 03;10:600
references.pmid: 21047392
references.citation: Clin Cancer Res. 2010 Jul 15;16(14):3760-8
references.pmid: 20501620
references.citation: Lung Cancer. 2005 Jun;48(3):307-13
references.pmid: 15892998
references.citation: Thorax. 2007 Jul;62(7):565-8
references.pmid: 17327260
references.citation: Chest. 2003 Jun;123(6):2115-23
references.pmid: 12796197
references.citation: Int J Cancer. 2010 Dec 15;127(12):2870-8
references.pmid: 21351266
references.citation: J Clin Oncol. 2008 Nov 1;26(31):5060-6
references.pmid: 18794547
references.citation: Cell Mol Life Sci. 2012 Oct;69(19):3341-3350
references.pmid: 22689099
references.citation: Genet Test Mol Biomarkers. 2013 May;17(5):359-66
references.pmid: 23387316
references.citation: Mod Pathol. 2010 Aug;23(8):1157-64
references.pmid: 20526284
references.citation: J Thorac Oncol. 2009 Sep;4(9):1060-5
references.pmid: 19704335
references.citation: Immunol Rev. 2002 Oct;188:122-35
references.pmid: 12445286
references.citation: Clin Chem. 2002 Nov;48(11):1931-7
references.pmid: 12406978
references.citation: Sci Transl Med. 2010 Apr 7;2(26):26ra25
references.pmid: 20375364
references.citation: BMC Med. 2013 Jul 19;11:168
references.pmid: 23870182
references.citation: CA Cancer J Clin. 2013 Jan;63(1):11-30
references.pmid: 23335087
references.citation: Cancer Res. 2002 Apr 15;62(8):2370-7
references.pmid: 11956099
references.citation: Mayo Clin Proc. 1984 Jul;59(7):453-66
references.pmid: 6738113
references.citation: N Engl J Med. 2013 Jul 18;369(3):245-254
references.pmid: 23863051
references.citation: J Thorac Oncol. 2011 Aug;6(8):1336-44
references.pmid: 21642863