Predictive and prognostic biomarkers with therapeutic targets in breast,colorectal,and non-small cell lung cancers: A systemic review of current development,evidence,and recommendation
Restricted accessResearch articleFirst published online February, 2014
Predictive and prognostic biomarkers with therapeutic targets in breast,colorectal,and non-small cell lung cancers: A systemic review of current development,evidence,and recommendation
Appropriate evidence-based roles of prognostic and predictive biomarkers of known therapeutic targets in breast, colorectal, and non-small cell lung cancers in adults are reviewed, with summary of evidence for use and recommendation. Current development in biomarker studies is also discussed. Computerized literature searches of PubMed (National Library of Medicine), the Cochrane Collaboration Library, and commonly accepted US and international guidelines (American Society of Clinical Oncology, European Society for Medical Oncology, and National Comprehensive Cancer Network) were performed from 2001 to 2012. Literature published before 2001 was noted for historical interest but not evaluated. Literature review was focused on available systematic reviews and meta-analyses of published predictive (associated with treatment response and/or efficacy) and prognostic (associated with disease outcome) biomarkers of known therapeutic targets in colorectal, breast, and non-small cell lung cancers. In general, significant health outcomes (e.g. predicted response to therapy, overall survival, disease-free survival, quality of life, lesser toxicity, and cost-effectiveness) were used for making recommendations. Four breast cancer biomarkers were evaluated, two of which (2D6 genotyping, Oncotype Dx) were considered emerging with insufficient evidence. Seven colorectal cancer biomarkers were evaluated, five of which (EGFR gene expression, K-ras G13D gene mutation, B-raf V600E gene mutation, dihydropyrimidine dehydrogenase deficiency, and UGT1A1 genotyping) were considered emerging. Seven non-small cell lung cancer biomarkers were evaluated, five of which were emerging (EGFR gene expression, ERCC gene expression, RRM1 gene expression, K-ras gene mutation, and TS gene expression). Of all 18 biomarkers evaluated, the following showed evidence of clinical utility and were recommended for routine use in practice: ER/PR and HER2 for breast cancer; K-ras gene mutation (except G13D gene mutation) for colorectal cancer; mismatch repair deficiency or microsatellite instability for colorectal cancer; and EGFR and EML4-ALK gene mutations for non-small cell lung. Not all recommendations for these biomarkers were uniformly supported by all guidelines.
AtkinsonAJColburnWADeGruttolaVG. Biomarkers Definitions Working Group. Biomarkers and surrogate end points: preferred definitions and conceptual framework. Clin Pharmacol Ther2001; 69: 89–95.
2.
SlamonDJClarkGMWongSG. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science1987; 235: 177–182.
3.
ChauCHRixeOMcLeodH. Validation of analytic methods for biomarkers used in drug development. Clin Cancer Res2008; 14: 5967–5976.
4.
McDermottUDowningJRStrattonMR. Genomics and the continuum of cancer care. N Engl J Med2011; 364: 340–350.
5.
Raman G, Wallace B, Patel K, et al. Technology assessment: update of horizon scans of genetic tests currently available for clinical use in cancers. Final report. 15 April 2011. Rockville, MD: Agency for Healthcare Research and Quality, http://www.cms.gov/Medicare/Coverage/DeterminationProcess/downloads/id81TA.pdf (2011, accessed 27 October 2012).
6.
TeutschSBradleyLPalomakiGE. The evaluation of genomic applications in practice and prevention (EGAPP) initiative: methods of the EGAPP Working Group. Genet Med2009; 11: 3–14.
7.
ShiroimaTMotooYTsutaniK. Cost-effectiveness analysis of kras testing and cetuximab as last-line therapy for colorectal cancer. Mol Diag Ther2010; 14: 375–384.
8.
AllredDCCarlsonRWBerryDA. NCCN Task Force Report: Estrogen receptor and progesterone receptor testing in breast cancer by immunohistochemistry. J Natl Compr Canc Netw (JNCCN)2009; 7(Suppl. 6): S1–S21.
9.
HammondMEHayesDFDowsettM. American Society of Clinical Oncology-College of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer. J Clin Oncol2010; 28: 2784–2795.
AebiSDavidsonTGruberG. Primary breast cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol2011; 22(Suppl. 6): vi12–vi24.
12.
CardosoFHarbeckNFallowfieldL. Locally recurrent or metastatic breast cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol2012; 23(Suppl. 7): vii11–vii19.
13.
HarrisLFritscheHMennelR. American Society of Clinical Oncology 2007 update of recommendations for the use of tumor markers in breast cancer. J Clin Oncol2007; 25: 5287–5312.
14.
Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group. Recommendations from the EGAPP Working Group: can tumor gene expression profiling improve outcomes in patients with breast cancer?Genet Med2009; 11: 66–73.
15.
AllegraCJJessupJMSomerfieldMR. American Society of Clinical Oncology provisional clinical opinion: Testing for KRAS gene mutations in patients with metastatic colorectal carcinoma to predict response to anti– epidermal growth factor monoclonal antibody therapy. J Clin Oncol2009; 27: 2091–2096.
LockerGHamiltonSHarrisJ. American Society of Clinical Oncology 2006 update of recommendations for the use of tumor markers in gastrointestinal cancer. J Clin Oncol2006; 24: 5513–5527.
18.
van CutsemENordingerBCervantesA. Advanced colorectal cancer: ESMO clinical practice guidelines for treatment. Ann Oncol2010; 21(Suppl. 5): v93–v97.
19.
LabiancaRNordingerBBerettaG. Primary colon cancer: ESMO clinical practice guidelines for diagnosis, adjuvant treatment and follow-up. Ann Oncol2010; 21(Suppl. 5): v70–v77.
20.
KeedyVLTeminSSomerfieldM. American Society of Clinical Oncology provisional clinical opinion: epidermal growth factor receptor (EGFR) mutation testing for patients with advanced non-small-cell lung cancer considering first-line EGFR tyrosine kinase inhibitor therapy. J Clin Oncol2011; 29: 2121–2127.
CrinoLWederWvan MeerbeeckJ. Early stage and locally advanced (non-metastatic) non-small-cell lung cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol2010; 21(Suppl. 5): v103–v115.
23.
PetersSAdjeiAAGridelliC. Metastatic non-small-cell lung cancer (NSCLC): ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol2012; 23(Suppl. 7): vii56–vii64.
24.
RosellRMoranTQueraltC. Screening for epidermal growth factor receptor mutations in lung cancer. N Engl J Med2009; 361: 958–967.
25.
SequistLVMartinRGSpigelD. First line gefitinib in patients with advanced non-small cell lung cancer harboring somatic EGFR mutations. J Clin Oncol2008; 26(15): 2442–2449.
26.
TsaoMSSakuradaACutzJC. Erlotinib in lung cancer-molecular and clinical predictors of outcome. N Engl J Med2005; 353: 133–144.
27.
ScrothWSGoetzMPHamannU. Association between CYP2D6 polymorphisms and outcomes among women with early stage breast cancer treated with tamoxifen. JAMA2009; 302: 1429–1436.
28.
HoskinsJMCareyLAMcLeodHL. CYP 2D6 and tamoxifen: DNA matters in breast cancer. Nat Rev Cancer2009; 9: 576–586.
29.
Rae JM, Drury S, Hayes DF, et al. Lack of correlation between gene variants in tamoxifen metabolizing enzymes with primary end points in the ATAC trial. In: Proceedings of the San Antonio breast cancer symposium 2010, San Antonio, TX, 8–12 December 2010, Abstract no. S1–S7. Philadelphia, PA: American Association for Cancer Research.
30.
Leyland-Jones B, Regan MM, Bonzyk M, et al. Outcome according to CYP2D6 genotype among postmenopausal women with endocrine-responsive early invasive breast cancer randomized in the BIG 1-98 trial. In: Proceedings of the San Antonio breast cancer symposium 2010, San Antonio, TX, 8–12 December 2010, Abstract no. S1-S8. Philadelphia, PA: American Association for Cancer Research.
31.
PechatananKJaruhathaiSAtivitavasT. Cytochrome P450 2D6 polymorphisms of Thai patients with breast cancer and their outcomes of adjuvant tamoxifen. J Clin Oncol2011; 29(Suppl.): e11037–e11037.
32.
AlbainKSBarlowWEShakS. prognostic and predictive value of the 21-gene recurrence score assay in postmenopausal women with node-positive, oestrogen-receptor-positive breast cancer on chemotherapy: a retrospective analysis of a randomized trial. Lancet Oncol2010; 11: 55–65.
33.
National Cancer Institute (NCI). Hormone therapy with or without combination chemotherapy in treating women who have undergone surgery for node-negative breast cancer (the TAILORx trial). 2006. Bethesda, MD: National Cancer Institute, http://clinicaltrials.gov/ct2/show/NCT00310180 (2006, accessed 1 November 2012).
34.
Di LeoADesmedtCBartlettJM. HER2 and TOP2A as predictive markers for anthracycline-containing chemotherapy regimens as adjuvant treatment of breast cancer: a meta-analysis of individual patient data. Lancet Oncol2011; 12: 1134–1142.
35.
Di LeoAGancbergDLarsimontD. HER-2 amplification and topisomerase IIalpha gene aberrations as predictive biomarkers in node-positive breast cancer patients randomly treated with either an anthracycline-based therapy or with cychophosphamide, methotrexate and 5-fluorouracil. Clin Cancer Res2002; 8: 1107–1116.
36.
HechtJRMitchellENeubauerMA. Lack of correlation between epidermal growth factor receptor status and response to Panitumumab monotherapy in metastatic colorectal cancer. Clin Cancer Res2010; 16: 2205–2213.
37.
ChungKYShiaJKemenyNE. Cetuximab shows activity in colorectal cancer patients with tumors that do not express the epidermal growth factor receptor by immunohistochemistry. J Clin Oncol2005; 23: 1803–1810.
38.
Bokemeyer C, Kohne C, Rougier P, et al. Cetuximab with chemotherapy (CT), as first line treatment for metastatic colorectal cancer (mCRC): analysis of the CRYSTAL and OPUS studies according to KRAS and BRAF mutation status. In: ASCO meeting abstracts, Chicago, IL, 4–8 June 2010. J Clin Oncol 2010; 28(Suppl. 15): 3506.
39.
De RoockWJonkerDJDi NicolantonioF. Association of KRAS p.G13D mutation with outcome in patients with chemotherapy-refractory metastatic colorectal cancer treated with cetuximab. JAMA2010; 304: 1812–1820.
40.
SamowitzWSCurtinKSchafferD. Relationship of Ki-ras mutations in colon cancers to tumor location, stage, and survival: a population-based study. Cancer Epidemiol Biomarkers Prev2000; 9: 1193–1197.
41.
WangCvan RijnsoeverMGrieuF. Prognostic significance of microsatellite instability and Ki-ras mutation type in stage II colorectal cancer. Oncology2003; 64: 259–265.
42.
LindorNMPetersenGMHadleyDW. Recommendations for the care of individuals with an inherited predisposition to Lynch Syndrome- a systematic review. JAMA2006; 296: 507–517.
43.
BolandCRThibodeauSNHamiltonSR. A National Cancer Institute workshop on microsatellite instability for cancer detection and familial predisposition: development of international criteria for the determination of microsatellite instability in colorectal cancer. Cancer Res1998; 58: 5248–5257.
44.
RibicCMSargentDJMooreMJ. Tumor microsatellite- instability status as a predictor of benefit from fluorouracil-based adjuvant chemotherapy for colon cancer. N Engl J Med2003; 349: 247–257.
45.
SargentDJMarsoniSMongesG. Defective mismatch repair as a predictive biomarker for lack of efficacy of fluorouracil-based adjuvant therapy in colon cancer. J Clin Oncol2010; 28: 3219–3226.
46.
PopatSHubnerRHoulstonRS. Systemic review of microsatellite instability and colorectal cancer prognosis. J Clin Oncol2005; 23: 609–618.
47.
van KuilenburgAB. Dihydropyrimidine dehydrogenase and the efficacy and toxicity of 5–fluorouracil. Eur J Cancer2004; 40: 939–950.
48.
EzzeldinHHDiasioRB. Predicting fluorouracil toxicity: can we finally do it?J Clin Oncol2008; 26: 2080–2082.
49.
LyerLDasSJanischL. UGT1A1*28 polymorphism as a determinant of irinotecan disposition and toxicity. Pharmacogenomics J2002; 2: 43–47.
50.
HoskinsJMGoldbergRMQuP. UGT1A1*28 genotype and irinotecan-induced neutropenia: dose matters. J Natl Cancer Inst2007; 99: 1290–1295.
51.
LiuCYChenPMChiouTJ. UGT1A1*28 polymorphism predicts irinotecan-induced severe toxicities without affecting treatment outcome and survival in patients with metastatic colorectal carcinoma. Cancer2008; 112: 1932–1940.
52.
MokTWuY-LThongprasertS. Phase III, randomized, open-label, first-line study of gefitinib (G) vs. carboplatin/paclitaxel (C/P) in clinically selected patients (pts) with advanced non-small-cell lung cancer (NSCLC) (IPASS). Ann Oncol2008; 19(Suppl. 8): 1–4.
53.
HerbstRSPragerDHermannR. TRIBUTE: a phase III trial of erlotinib hydrochloride (OSI-774) combined with carboplatin and paclitaxel chemotherapy in advanced non-small cell lung cancer. J Clin Oncol2005; 23: 5892–5899.
54.
EberhardDAJohnsonBEAmlerLC. Mutations in the epidermal growth factor receptor and in KRAS are predictive and prognostic indicators in patients with non-small-cell lung cancer treated with chemotherapy alone and in combination with erlotinib. J Clin Oncol2005; 23: 5900–5909.
55.
OlaussenKADunantAFouretP. DNA repair by ERCC1 in non small–cell lung cancer and cisplatin-based adjuvant chemotherapy. N Engl J Med2006; 355: 983–991.
56.
LordRVNBrabenderJGandaraD. Low ERCC1 expression correlates with prolonged survival after cisplatin plus gemcitabine chemotherapy in non-small cell lung cancer. Clin Cancer Res2002; 8: 2286–2291.
57.
Bepler G, Li X, Schell M, et al. Predictive value of RRM1 and ERCC1 protein levels in a prospective community-based trial of gemcitabine/carboplatin (GC) vs. gemcitabine (G) alone. In: ASCO meeting abstracts, Chicago, IL, 30 May-3 June 2008. J Clin Oncol 2008; 26: 8033.
58.
CeppiPVolanteMNovelloS. ERCC1 and RRM1 gene expressions but not EGFR are predictive of shorter survival in advanced non-small cell lung cancer treated with cisplatin and gemcitabine. Ann Oncol2006; 17: 1818–1825.
59.
RosellRDanenbergKDAlberolaV. Ribonucleotide reductase messenger RNA expression and survival in gemcitabine/cisplatin-treated advanced non-small cell lung cancer patients. Clin Cancer Res2004; 10: 1318–1325.
60.
HarveyJMClarkGMOsborneCK. Estrogen receptor status by immunohistochemistry is superior to the ligand –binding assay for predicting response to adjuvant endocrine therapy in breast cancer. J Clin Oncol1999; 17: 1474–1481.
61.
GrahamJDRomanSDMcGowanE. Preferential stimulation of human progesterone receptor B expression by estrogen in T-47D human breast cancer cells. J Biol Chem1995; 270: 30693–30700.
62.
Early Breast cancer Trialists’ Collaborative Group (EBCTCG). Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet2005; 365: 1687–1717.
63.
LiuSchiaSMehlE. Progesterone receptor is a significant factor associated with clinical outcome and effect of adjuvant tamoxifen therapy in breast cancer patients. Breast Cancer Res treat2010; 119: 53–61.
64.
StendahlMRydenLNordenskjoldB. High progesterone receptor expression correlates to the effect of adjuvant tamoxifen in premenopausal breast cancer patients. Clin Cancer Res2006; 12: 4614–4618.
65.
DowsettMCuzickJIngleJ. Meta-analysis of breast cancer outcomes in adjuvant trials of aromatase inhibitors versus tamoxifen. J Clin Oncol2010; 28: 508–518.
66.
FisherBRedmondCFisherER. Relative worth of estrogen or progesterone receptor and pathologic characteristics of differentiation as indicators of prognosis in node negative breast cancer patients: findings from national Surgical Adjuvant Breast and Bowel Project protocol B-06. J Clin Oncol1988; 6: 1076–1087.
67.
ZhengWQLuJZhengJM. Variation of ER status between primary and metastatic breast cancer and relationship of p53 expression. Steroids2001; 66: 905–910.
68.
Franco A, Col N and Chlebowski RT. Discordance in estrogen (ER) and progestin receptor (PR) status between primary metastatic breast cancer: a meta-analysis. In: ASCO meeting abstracts, Chicago, IL, 4–8 June 2004. J Clin Oncol 2004; 22(Suppl. 14): 539.
69.
De PlacidSDe LaurentiisMCarlomagnoC. Twenty-year results of the Naples GUN randomized trial: predictive factor of tamoxifen efficacy in early breast cancer. Clin Cancer Res2003; 9: 1039–1046.
70.
ProwellTMArmstrongDK. Selecting endocrine therapy for breast cancer: what role does HER-2/neu status play?Semin Oncol2006; 33: 681–687.
71.
SymmansWFHatzisCSotiriouC. Genomic index of sensitivity to endocrine therapy for breast cancer. J Clin Oncol2010; 28: 4111–4119.
72.
BursteinHJPrestrudAASeidenfeldJ. American Society of Clinical Oncology clinical practice guideline: update on adjuvant endocrine therapy for women with hormone receptor-positive breast cancer. J Clin Oncol2010; 28: 77–82.
73.
BerryDACirrincioneCHendersonIC. Estrogen-receptor status and outcomes of modern chemotherapy for patients with node-positive breast cancer. JAMA2006; 295: 1658–1667.
74.
SalomonDSBrandtRCiardielloF. Epidermal growth factor-related peptides and their receptors in human malignancies. Crit Rev Oncol Hematol1995; 19: 183–232.
JoensuuHKellokumpu-LehtinenPLBonoP. Adjuvant docetaxel or vinorelbine with or without trastuzumab for breast cancer. N Engl J Med2006; 354: 809–820.
77.
SlamonDJLeyland-JonesBShakS. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med2001; 344: 783–792.
78.
AlvarezRValeroVHortobagyiG. Emerging targeted therapies for breast cancer. J Clin Oncol2010; 28: 3366–3379.
79.
BarnettCM. Everolimus: targeted therapy on the horizon for the treatment of breast cancer. Pharmacotherapy2012; 32: 383–396.
80.
BaselgaJCamponeMPiccartM. Everolimus in postmenopausal hormone-receptor–positive advanced breast cancer. N Engl J Med2012; 366: 520–529.
81.
BlackwellKIBursteinHJStornioloAM. Randomized study of lapatinib alone or in combination with trastuzumab in women with ErbB-2 positive, trastuzumab-refractory metastatic breast cancer. J Clin Oncol2010; 28: 1124–1130.
van CutsemEKöhneCHLángI. Cetuximab plus irinotecan, fluorouracil, and leucovorin as first-line treatment for metastatic colorectal cancer: updated analysis of overall survival according to tumor KRAS and BRAF mutation status. J Clin Oncol2011; 29: 2011–2019.
84.
HutchinsGSouthwardKHandleyK. Value of mismatch repair, KRAS, and BRAF mutations in predicting recurrence and benefits from chemotherapy in colorectal cancer. J Clin Oncol2011; 29: 1261–1270.
85.
Peréz-SolerRSaltzL. Cutaneous adverse effects with HER1/EGFR targeted agents: is there a silver lining?J Clin Oncol2005; 23: 5235–5246.
86.
Shah A, Chen E, Jonker D, et al. A phase II clinical trial of nimotuzumab, an EGFR monoclonal antibody in metastatic colorectal cancer. In: Proceedings of the 2009 gastrointestinal cancers symposium, San Francisco, CA, 15–17 January 2009, Abstract no. 358. Alexandria, VA: American Society of Clinical Oncology.
87.
KrasinskasAM. EGFR signaling in colorectal carcinoma. Pathol Res Int. Epub ahead of print 14 February 2011. DOI: 10.4061/2011/932932.
88.
LenzHJLeichmanCGDanenbergKD. Thymidylate synthase mRNA level in adenocarcinoma of the stomach: a predictor for primary tumor response and overall survival. J Clin Oncol1996; 14: 176–182.
89.
WeiXElizondoGSaponeA. Characterization of the human dihydropyrimidine dehydrogenase gene among. Genomics1998; 51: 391–400.
90.
KoopmanMVenderboschSNagtegaalID. A review on the use of molecular markers of cytotoxic therapy for colorectal cancer, what have we learned?Eur J Cancer2009; 45: 1935–1949.
91.
CernyTBarnesDMHasletonP. Expression of epidermal growth factor receptor (EGF-R) in human lung tumors. Br J Cancer1986; 54: 265–269.
92.
LynchTJBellDWSordellaR. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small cell lung cancer to gefitinib. N Engl J Med2004; 350: 2129–2139.
93.
SocinskiMA. The emerging role of biomarkers in advanced non-small-cell lung cancer. Clin Lung Cancer2010; 11: 149–159.
94.
MaemondoMInoueAKobayashiK. Gefitinib or chemotherapy for non-small cell lung cancer with mutated EGFR. N Engl J Med2010; 362: 2380–2388.
95.
JackmanDMYeapBYSequistLV. Exon 19 deletion mutations of epidermal growth factor receptor are associated with prolonged survival in non-small cell lung cancer patients treated with gefitinib or erlotinib. Clin Cancer Res2006; 12: 3908–3914.
96.
TaronMIchinoseYRosellR. Activating mutations in the tyrosine kinase domain of the epidermal growth factor receptor are associated with improved survival in gefitinib-treated chemorefractory lung adenocarcinomas. Clin Cancer Res2005; 11: 5878–5885.
97.
LinardouHDahabrehIJKanaloupitiD. Assessment of somatic Kras mutations as a mechanism associated with resistance to EGFR targeted agents: a systemic review and meta-analysis of studies in advanced non-small cell lung cancer and metastatic colorectal cancer. Lancet Oncol2008; 9(10): 962–972.
98.
HirschFRVarella-GarciaMCappuzooF. Combination of EGFR gene copy number and protein expression predicts outcome for advanced non-small cell lung cancer patients treated with gefitinib. Ann Oncol2007; 18: 752–760.
99.
SequistLVWaltmanBADias-SantagataD. Genotypic and histological evolution of lung cancers acquiring resistance to EGFR inhibitors. Sci Transl Med2011; 3: 75ra26–75ra26.
100.
OxnardGRJannePA. Kras wild-type lung cancer: a moving target in an era of genotype migration. J Clin Oncol2012; 30: 3322–3324.
101.
YangJC-HShihJ-YSuW-C. Afatinib for patients with lung adenocarcinoma and epidermal growth factor mutations (LUX-Lung 2): a phase 2 trial. Lancet Oncol2012; 13: 539–548.
102.
LiDAmbrogioLShimamuraT. BIBW 2992, an irreversible EGFR/HER2 inhibitor highly effective in preclinical lung cancer models. Oncogene2008; 27: 4702–4711.
103.
HeymachJVSaintignyPKimES. Gene expression signatures predictive of clinical outcome and tumor mutations in refractory NSCLC patients in the BATTLE trial (Biomarker-integrated Approaches of Targeted Therapy for Lung Cancer Elimination). Cancer Res2011; 71: LB-88–LB-88.
104.
SodaMChoiYLEnomotoM. Identification of the transforming EML4- ALK fusion gene in non-small-cell lung cancer. Nature2007; 448: 561–566.
105.
TakahashiTSonobeMKobayashiM. Clinicopathologic features of non-small-cell lung cancer with EML4-ALK fusion gene. Ann Surg Oncol2010; 17: 889–897.
106.
FordePMRudinCM. Crizotinib in the treatment of non-small-cell lung cancer. Expert Opin Pharmacother2012; 13: 1195–1201.
AhrendtSADeckerPAAlawiEA. Cigarette smoking is strongly associated with mutations of the k-ras gene in patients with primary adenocarcinoma of the lung. Cancer2001; 92: 1525–1530.
109.
MascauxCIanninoNMartinB. The role of RAS oncogene in survival of patients with lung cancer: a systemic review of the literature with meta-analysis. Br J Cancer2005; 92: 131–139.
110.
MillerVARielyGJZakowskiMF. Molecular characteristics of bronchioalveloar carcinoma and adenocarcinoma, bronchioalveloar carcinoma subtype, predict response to erlotinib. J Clin Oncol2008; 26: 1472–1478.
111.
RodenhuisSSlebosRJC. The ras oncogenes in human lung cancer. Am J Respir Crit Care Med1990; 142. (Part 2): S27–S30.
112.
ZhuCQda Cunha SantosGDingK. Role of KRAS and EGFR as biomarkers of response to erlotinib in national cancer Institute of Canada Clinical Trials Group Study BR.21. J Clin Oncol2008; 26: 4268–4275.
113.
MurukeshNDiveCJaysonGC. Biomarkers of antiangiogenesis and their role in the development of VEGF inhibitors. Br J Cancer2010; 102: 8–18.
114.
CaoY. Antiangiogenic cancer therapy. Semin Cancer Biol2004; 14(2): 139–145.
115.
JubbAMHurwitzHIBaiW. Impact of vascular endothelial growth factor-A expression, thrombospondin-2 expression, and microvessel density on the treatment effect of bevacizumab in metastatic colorectal cancer. J Clin Oncol2006; 24: 217–227.
116.
LongoRGaspariniG. Challenges for patient selection with VEGF inhibitors. Cancer Chemother Pharmacol2007; 60: 151–170.
117.
HechtJRMitchellEChidiacT. A randomized phase IIIB trial of chemotherapy, bevacizumab, and panitumumab compared with chemotherapy and bevacizumab alone for metastatic colorectal cancer. J Clin Oncol2009; 27: 672–680.
118.
TolJKoopmanMCatsA. Chemotherapy, bevacizumab, and cetuximab in metastatic colorectal cancer. N Engl J Med2009; 360: 563–572.
