Predictive and prognostic markers in the treatment of metastatic colorectal cancer (mCRC): Personalized medicine at work

Hematology/Oncology Clinics of North America

Volumn 29, Issue 1, 2015, Pages 43-60

  Stintzing, Sebastian ^a   Stremitzer, Stefan ^a   Sebio, Ana ^a   Lenz, Heinz Josef ^a  

^a UNIVERSITY OF SOUTHERN CALIFORNIA   (United States)

Author keywords

Biomarker; BRAF; Colorectal cancer; KRAS; NRAS

Indexed keywords

AMPHIREGULIN; B RAF KINASE; EPIDERMAL GROWTH FACTOR RECEPTOR; EPIDERMAL GROWTH FACTOR RECEPTOR ANTIBODY; EPIREGULIN; FLUOROURACIL; IRINOTECAN; K RAS PROTEIN; OXALIPLATIN; PHOSPHATIDYLINOSITOL 3,4,5 TRISPHOSPHATE 3 PHOSPHATASE; PHOSPHATIDYLINOSITOL 4,5 BISPHOSPHATE 3 KINASE; TUMOR MARKER;

ANTIANGIOGENIC THERAPY; CANCER PROGNOSIS; EXON; GENE MUTATION; HUMAN; METASTATIC COLORECTAL CANCER; PERSONALIZED MEDICINE; PREDICTION; REVIEW; SIGNAL TRANSDUCTION; ANIMAL; COLORECTAL NEOPLASMS; DRUG EFFECTS; GENETICS; METASTASIS; MOLECULARLY TARGETED THERAPY; MORTALITY; MUTATION; PATHOLOGY; PROGNOSIS;

ANIMALS; COLORECTAL NEOPLASMS; HUMANS; INDIVIDUALIZED MEDICINE; MOLECULAR TARGETED THERAPY; MUTATION; NEOPLASM METASTASIS; PROGNOSIS; SIGNAL TRANSDUCTION; TUMOR MARKERS, BIOLOGICAL;

EID: 84919339616     PISSN: 08898588     EISSN: 15581977     Source Type: Journal    
DOI: 10.1016/j.hoc.2014.09.009     Document Type: Review

References (96)

1. Siegel R., Ma J., Zou Z., et al. Cancer statistics, 2014. CA Cancer J Clin 2014, 64(1):9-29.
2. Van Cutsem E., Kohne C.H., Lang I., et al. 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. JClin Oncol 2011, 29(15):2011-2019.
3. Bennouna J., Sastre J., Arnold D., et al. Continuation of bevacizumab after first progression in metastatic colorectal cancer (ML18147): a randomised phase 3 trial. Lancet Oncol 2013, 14(1):29-37.
4. O'Connell J.B., Maggard M.A., Ko C.Y. Colon cancer survival rates with the new American Joint Committee on Cancer sixth edition staging. JNatl Cancer Inst 2004, 96(19):1420-1425.
5. Tournigand C., Andre T., Achille E., et al. FOLFIRI followed by FOLFOX6 or the reverse sequence in advanced colorectal cancer: a randomized GERCOR study. JClin Oncol 2004, 22(2):229-237.
6. Saltz L.B., Clarke S., Diaz-Rubio E., et al. Bevacizumab in combination with oxaliplatin-based chemotherapy as first-line therapy in metastatic colorectal cancer: a randomized phase III study. JClin Oncol 2008, 26(12):2013-2019.
7. Cassidy J., Clarke S., Diaz-Rubio E., et al. XELOX vs FOLFOX-4 as first-line therapy for metastatic colorectal cancer: NO16966 updated results. Br J Cancer 2011, 105(1):58-64.
8. Hurwitz H., Fehrenbacher L., Novotny W., et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. NEngl J Med 2004, 350(23):2335-2342.
9. Bokemeyer C., Bondarenko I., Makhson A., et al. Fluorouracil, leucovorin, and oxaliplatin with and without cetuximab in the first-line treatment of metastatic colorectal cancer. JClin Oncol 2009, 27(5):663-671.
10. Douillard J.Y., Siena S., Cassidy J., et al. Randomized, phase III trial of panitumumab with infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX4) versus FOLFOX4 alone as first-line treatment in patients with previously untreated metastatic colorectal cancer: the PRIME study. JClin Oncol 2010, 28(31):4697-4705.
11. Stintzing S., Lenz H.J. Protein kinase inhibitors in metastatic colorectal cancer. Let's pick patients, tumors, and kinase inhibitors to piece the puzzle together!. Expert Opin Pharmacother 2013, 14(16):2203-2220.
12. Grothey A., Van Cutsem E., Sobrero A., et al. Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): an international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet 2013, 381(9863):303-312.
13. Joulain F., Proskorovsky I., Allegra C., et al. Mean overall survival gain with aflibercept plus FOLFIRI vs placebo plus FOLFIRI in patients with previously treated metastatic colorectal cancer. Br J Cancer 2013, 109(7):1735-1743.
14. Falcone A., Ricci S., Brunetti I., et al. Phase III trial of infusional fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) compared with infusional fluorouracil, leucovorin, and irinotecan (FOLFIRI) as first-line treatment for metastatic colorectal cancer: the Gruppo Oncologico Nord Ovest. JClin Oncol 2007, 25(13):1670-1676.
15. Schmoll H.J., Van Cutsem E., Stein A., et al. ESMO Consensus Guidelines for management of patients with colon and rectal cancer. A personalized approach to clinical decision making. Ann Oncol 2012, 23(10):2479-2516.
16. Heinemann V., Stintzing S., Kirchner T., et al. Clinical relevance of EGFR- and KRAS-status in colorectal cancer patients treated with monoclonal antibodies directed against the EGFR. Cancer Treat Rev 2009, 35(3):262-271.
17. Van Cutsem E., Peeters M., Siena S., et al. Open-label phase III trial of panitumumab plus best supportive care compared with best supportive care alone in patients with chemotherapy-refractory metastatic colorectal cancer. JClin Oncol 2007, 25(13):1658-1664.
18. Jonker D.J., O'Callaghan C.J., Karapetis C.S., et al. Cetuximab for the treatment of colorectal cancer. NEngl J Med 2007, 357(20):2040-2048.
19. Cunningham D., Humblet Y., Siena S., et al. Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. NEngl J Med 2004, 351(4):337-345.
20. Lievre A., Bachet J.B., Le Corre D., et al. KRAS mutation status is predictive of response to cetuximab therapy in colorectal cancer. Cancer Res 2006, 66(8):3992-3995.
21. Stintzing S., Fischer von Weikersthal L., Decker T., et al. FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab as first-line treatment for patients with metastatic colorectal cancer-subgroup analysis of patients with KRAS: mutated tumours in the randomised German AIO study KRK-0306. Ann Oncol 2012, 23(7):1693-1699.
22. Chen C.C., Er T.K., Liu Y.Y., et al. Computational analysis of KRAS mutations: implications for different effects on the KRAS p.G12D and p.G13D mutations. PLoS One 2013, 8(2):e55793.
23. Irahara N., Baba Y., Nosho K., et al. NRAS mutations are rare in colorectal cancer. Diagn Mol Pathol 2010, 19(3):157-163.
24. Douillard J.Y., Oliner K.S., Siena S., et al. Panitumumab-FOLFOX4 treatment and RAS mutations in colorectal cancer. NEngl J Med 2013, 369(11):1023-1034.
25. Malumbres M., Barbacid M. RAS oncogenes: the first 30 years. Nat Rev Cancer 2003, 3(6):459-465.
26. Tejpar S., Lenz H.J., Kohne C.H., et al. Effect of KRAS and NRAS mutations on treatment outcomes in patients with metastatic colorectal cancer (mCRC) treated first-line with cetuximab plus FOLFOX4: New results from the OPUS study. JClin Oncol 2014, 32(Suppl 3). [abstract: LBA444].
27. Heinemann V., von Weikersthal L.F., Decker T., et al. FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab as first-line treatment for patients with metastatic colorectal cancer (FIRE-3): a randomised, open-label, phase 3 trial. Lancet Oncol 2014, 15(10):1065-1075.
28. Brodowicz T., Vrbanec D., Kaczirek K., et al. FOLFOX4 plus cetuximab administered weekly or every two weeks in first-line treatment of patients with KRAS and NRAS wild-type (wt) metastatic colorectal cancer (mCRC). JClin Oncol 2014, 32(Suppl 3). [abstract: LBA391].
29. Schubbert S., Shannon K., Bollag G. Hyperactive Ras in developmental disorders and cancer. Nat Rev Cancer 2007, 7(4):295-308.
30. Zuo Z., Chen S.S., Chandra P.K., et al. Application of COLD-PCR for improved detection of KRAS mutations in clinical samples. Mod Pathol 2009, 22(8):1023-1031.
31. Anderson S.M. Laboratory methods for KRAS mutation analysis. Expert Rev Mol Diagn 2011, 11(6):635-642.
32. Janne P.A., Borras A.M., Kuang Y., et al. Arapid and sensitive enzymatic method for epidermal growth factor receptor mutation screening. Clin Cancer Res 2006, 12(3 Pt 1):751-758.
33. Li M., Diehl F., Dressman D., et al. BEAMing up for detection and quantification of rare sequence variants. Nat Methods 2006, 3(2):95-97.
34. Domagala P., Hybiak J., Sulzyc-Bielicka V., et al. KRAS mutation testing in colorectal cancer as an example of the pathologist's role in personalized targeted therapy: a practical approach. Pol J Pathol 2012, 63(3):145-164.
35. Lee S., Brophy V.H., Cao J., et al. Analytical performance of a PCR assay for the detection of KRAS mutations (codons 12/13 and 61) in formalin-fixed paraffin-embedded tissue samples of colorectal carcinoma. Virchows Arch 2012, 460(2):141-149.
36. Carotenuto P., Roma C., Rachiglio A.M., et al. Detection of KRAS mutations in colorectal carcinoma patients with an integrated PCR/sequencing and real-time PCR approach. Pharmacogenomics 2010, 11(8):1169-1179.
37. Basso M., Strippoli A., Orlandi A., et al. KRAS mutational status affects oxaliplatin-based chemotherapy independently from basal mRNA ERCC-1 expression in metastatic colorectal cancer patients. Br J Cancer 2013, 108(1):115-120.
38. Lin Y.L., Liau J.Y., Yu S.C., et al. KRAS mutation is a predictor of oxaliplatin sensitivity in colon cancer cells. PLoS One 2012, 7(11):e50701.
39. Schmiegel W., Reinacher-Schick A., Arnold D., et al. Capecitabine/irinotecan or capecitabine/oxaliplatin in combination with bevacizumab is effective and safe as first-line therapy for metastatic colorectal cancer: a randomized phase II study of the AIO colorectal study group. Ann Oncol 2013, 24(6):1580-1587.
40. Lin J.S., Webber E.M., Senger C.A., et al. Systematic review of pharmacogenetic testing for predicting clinical benefit to anti-EGFR therapy in metastatic colorectal cancer. Am J Cancer Res 2011, 1(5):650-662.
41. Sahin I.H., Kazmi S.M., Yorio J.T., et al. Rare though not mutually exclusive: a report of three cases of concomitant KRAS and BRAF mutation and a review of the literature. JCancer 2013, 4(4):320-322.
42. Tol J., Nagtegaal I.D., Punt C.J. BRAF mutation in metastatic colorectal cancer. NEngl J Med 2009, 361(1):98-99.
43. Richman S.D., Seymour M.T., Chambers P., et al. KRAS and BRAF mutations in advanced colorectal cancer are associated with poor prognosis but do not preclude benefit from oxaliplatin or irinotecan: results from the MRC FOCUS trial. JClin Oncol 2009, 27(35):5931-5937.
44. Price T.J., Hardingham J.E., Lee C.K., et al. Impact of KRAS and BRAF gene mutation status on outcomes from the phase III AGITG MAX trial of capecitabine alone or in combination with bevacizumab and mitomycin in advanced colorectal cancer. JClin Oncol 2011, 29(19):2675-2682.
45. Loupakis F., Cremolini C., Salvatore L., et al. FOLFOXIRI plus bevacizumab as first-line treatment in BRAF mutant metastatic colorectal cancer. Eur J Cancer 2014, 50(1):57-63.
46. Shen Y., Wang J., Han X., et al. Effectors of epidermal growth factor receptor pathway: the genetic profiling of KRAS, BRAF, PIK3CA, NRAS mutations in colorectal cancer characteristics and personalized medicine. PLoS One 2013, 8(12):e81628.
47. Seymour M.T., Brown S.R., Middleton G., et al. Panitumumab and irinotecan versus irinotecan alone for patients with KRAS wild-type, fluorouracil-resistant advanced colorectal cancer (PICCOLO): a prospectively stratified randomised trial. Lancet Oncol 2013, 14(8):749-759.
48. Stintzing S., Lenz H.J. Asmall cog in a big wheel: PIK3CA mutations in colorectal cancer. JNatl Cancer Inst 2013, 105(23):1775-1776.
49. Janku F., Lee J.J., Tsimberidou A.M., et al. PIK3CA mutations frequently coexist with RAS and BRAF mutations in patients with advanced cancers. PLoS One 2011, 6(7):e22769.
50. Liao X., Lochhead P., Nishihara R., et al. Aspirin use, tumor PIK3CA mutation, and colorectal-cancer survival. NEngl J Med 2012, 367(17):1596-1606.
51. Kothari N., Kim R.D., Gibbs P., et al. Regular aspirin (ASA) use and survival in patients with PIK3CA-mutated metastatic colorectal cancer (CRC). JClin Oncol 2014, 32(Suppl 3). [abstract: 386].
52. De Roock W., De Vriendt V., Normanno N., et al. KRAS, BRAF, PIK3CA, and PTEN mutations: implications for targeted therapies in metastatic colorectal cancer. Lancet Oncol 2011, 12(6):594-603.
53. Britten C.D. PI3K and MEK inhibitor combinations: examining the evidence in selected tumor types. Cancer Chemother Pharmacol 2013, 71(6):1395-1409.
54. Yang Z.Y., Wu X.Y., Huang Y.F., et al. Promising biomarkers for predicting the outcomes of patients with KRAS wild-type metastatic colorectal cancer treated with anti-epidermal growth factor receptor monoclonal antibodies: a systematic review with meta-analysis. Int J Cancer 2013, 133(8):1914-1925.
55. Majek O., Gondos A., Jansen L., et al. Sex differences in colorectal cancer survival: population-based analysis of 164,996 colorectal cancer patients in Germany. PLoS One 2013, 8(7):e68077.
56. Molinari F., Frattini M. Functions and regulation of the PTEN gene in colorectal cancer. Front Oncol 2013, 3:326.
57. Sood A., McClain D., Maitra R., et al. PTEN gene expression and mutations in the PIK3CA gene as predictors of clinical benefit to anti-epidermal growth factor receptor antibody therapy in patients with KRAS wild-type metastatic colorectal cancer. Clin Colorectal Cancer 2012, 11(2):143-150.
58. Danielsen S.A., Lind G.E., Bjornslett M., et al. Novel mutations of the suppressor gene PTEN in colorectal carcinomas stratified by microsatellite instability- and TP53 mutation-status. Hum Mutat 2008, 29(11):E252-E262.
59. Sartore-Bianchi A., Martini M., Molinari F., et al. PIK3CA mutations in colorectal cancer are associated with clinical resistance to EGFR-targeted monoclonal antibodies. Cancer Res 2009, 69(5):1851-1857.
60. Loupakis F., Pollina L., Stasi I., et al. PTEN expression and KRAS mutations on primary tumors and metastases in the prediction of benefit from cetuximab plus irinotecan for patients with metastatic colorectal cancer. JClin Oncol 2009, 27(16):2622-2629.
61. Tol J., Dijkstra J.R., Klomp M., et al. Markers for EGFR pathway activation as predictor of outcome in metastatic colorectal cancer patients treated with or without cetuximab. Eur J Cancer 2010, 46(11):1997-2009.
62. Khambata-Ford S., Garrett C.R., Meropol N.J., et al. Expression of epiregulin and amphiregulin and K-ras mutation status predict disease control in metastatic colorectal cancer patients treated with cetuximab. JClin Oncol 2007, 25(22):3230-3237.
63. Jacobs B., De Roock W., Piessevaux H., et al. Amphiregulin and epiregulin mRNA expression in primary tumors predicts outcome in metastatic colorectal cancer treated with cetuximab. JClin Oncol 2009, 27(30):5068-5074.
64. Jonker D.J., Karapetis C.S., Harbison C., et al. Epiregulin gene expression as a biomarker of benefit from cetuximab in the treatment of advanced colorectal cancer. Br J Cancer 2014, 110(3):648-655.
65. Stintzing S., Jung A., Kapaun C., et al. Amphiregulin and epiregulin expression predicts treatment efficacy in metastatic colorectal cancer (mCRC) patients treated with cetuximab plus CAPIRI or CAPOX: analysis of the German AIO CRC Group trial: KRK-0204. Ann Oncol 2011, 22(Suppl 5):v10-v18.
66. Lieu C.H., Tran H., Jiang Z.Q., et al. The association of alternate VEGF ligands with resistance to anti-VEGF therapy in metastatic colorectal cancer. PLoS One 2013, 8(10):e77117.
67. Vasudev N.S., Reynolds A.R. Anti-angiogenic therapy for cancer: current progress, unresolved questions and future directions. Angiogenesis 2014, 17:471-494.
68. Formica V., Palmirotta R., Del Monte G., et al. Predictive value of VEGF gene polymorphisms for metastatic colorectal cancer patients receiving first-line treatment including fluorouracil, irinotecan, and bevacizumab. Int J Colorectal Dis 2011, 26(2):143-151.
69. Kopetz S., Hoff P.M., Morris J.S., et al. Phase II trial of infusional fluorouracil, irinotecan, and bevacizumab for metastatic colorectal cancer: efficacy and circulating angiogenic biomarkers associated with therapeutic resistance. JClin Oncol 2010, 28(3):453-459.
70. Gianni L., Romieu G.H., Lichinitser M., et al. AVEREL: a randomized phase III trial evaluating bevacizumab in combination with docetaxel and trastuzumab as first-line therapy for HER2-positive locally recurrent/metastatic breast cancer. JClin Oncol 2013, 31(14):1719-1725.
71. Longley D.B., Harkin D.P., Johnston P.G. 5-Fluorouracil: mechanisms of action and clinical strategies. Nat Rev Cancer 2003, 3(5):330-338.
72. Walther A., Johnstone E., Swanton C., et al. Genetic prognostic and predictive markers in colorectal cancer. Nat Rev Cancer 2009, 9(7):489-499.
73. Diasio R.B., Johnson M.R. The role of pharmacogenetics and pharmacogenomics in cancer chemotherapy with 5-fluorouracil. Pharmacology 2000, 61(3):199-203.
74. Koopman M., Venderbosch S., van Tinteren H., et al. Predictive and prognostic markers for the outcome of chemotherapy in advanced colorectal cancer, a retrospective analysis of the phase III randomised CAIRO study. Eur J Cancer 2009, 45(11):1999-2006.
75. Vallbohmer D., Yang D.Y., Kuramochi H., et al. DPD is a molecular determinant of capecitabine efficacy in colorectal cancer. Int J Oncol 2007, 31(2):413-418.
76. Teh L.K., Hamzah S., Hashim H., et al. Potential of dihydropyrimidine dehydrogenase genotypes in personalizing 5-fluorouracil therapy among colorectal cancer patients. Ther Drug Monit 2013, 35(5):624-630.
77. Popat S., Matakidou A., Houlston R.S. Thymidylate synthase expression and prognosis in colorectal cancer: a systematic review and meta-analysis. JClin Oncol 2004, 22(3):529-536.
78. Pullarkat S.T., Stoehlmacher J., Ghaderi V., et al. Thymidylate synthase gene polymorphism determines response and toxicity of 5-FU chemotherapy. Pharmacogenomics J 2001, 1(1):65-70.
79. Kweekel D.M., Gelderblom H., Guchelaar H.J. Pharmacology of oxaliplatin and the use of pharmacogenomics to individualize therapy. Cancer Treat Rev 2005, 31(2):90-105.
80. Grothey A., Goldberg R.M. Areview of oxaliplatin and its clinical use in colorectal cancer. Expert Opin Pharmacother 2004, 5(10):2159-2170.
81. Fischer von Weikersthal L., Schalhorn A., Stauch M., et al. Phase III trial of irinotecan plus infusional 5-fluorouracil/folinic acid versus irinotecan plus oxaliplatin as first-line treatment of advanced colorectal cancer. Eur J Cancer 2011, 47(2):206-214.
82. Shirota Y., Stoehlmacher J., Brabender J., et al. ERCC1 and thymidylate synthase mRNA levels predict survival for colorectal cancer patients receiving combination oxaliplatin and fluorouracil chemotherapy. JClin Oncol 2001, 19(23):4298-4304.
83. Ruzzo A., Graziano F., Loupakis F., et al. Pharmacogenetic profiling in patients with advanced colorectal cancer treated with first-line FOLFOX-4 chemotherapy. JClin Oncol 2007, 25(10):1247-1254.
84. Baba H., Watanabe M., Okabe H., et al. Upregulation of ERCC1 and DPD expressions after oxaliplatin-based first-line chemotherapy for metastatic colorectal cancer. Br J Cancer 2012, 107(12):1950-1955.
85. Kanai M., Yoshioka A., Tanaka S., et al. Associations between glutathione S-transferase pi Ile105Val and glyoxylate aminotransferase Pro11Leu and Ile340Met polymorphisms and early-onset oxaliplatin-induced neuropathy. Cancer Epidemiol 2010, 34(2):189-193.
86. Lamas M.J., Duran G., Balboa E., et al. Use of a comprehensive panel of biomarkers to predict response to a fluorouracil-oxaliplatin regimen in patients with metastatic colorectal cancer. Pharmacogenomics 2011, 12(3):433-442.
87. Stoehlmacher J., Park D.J., Zhang W., et al. Association between glutathione S-transferase P1, T1, and M1 genetic polymorphism and survival of patients with metastatic colorectal cancer. JNatl Cancer Inst 2002, 94(12):936-942.
88. Lamas M.J., Duran G., Balboa E., et al. The value of genetic polymorphisms to predict toxicity in metastatic colorectal patients with irinotecan-based regimens. Cancer Chemother Pharmacol 2012, 69(6):1591-1599.
89. Cunningham D., Pyrhonen S., James R.D., et al. Randomised trial of irinotecan plus supportive care versus supportive care alone after fluorouracil failure for patients with metastatic colorectal cancer. Lancet 1998, 352(9138):1413-1418.
90. Douillard J.Y., Cunningham D., Roth A.D., et al. Irinotecan combined with fluorouracil compared with fluorouracil alone as first-line treatment for metastatic colorectal cancer: a multicentre randomised trial. Lancet 2000, 355(9209):1041-1047.
91. Cecchin E., Innocenti F., D'Andrea M., et al. Predictive role of the UGT1A1, UGT1A7, and UGT1A9 genetic variants and their haplotypes on the outcome of metastatic colorectal cancer patients treated with fluorouracil, leucovorin, and irinotecan. JClin Oncol 2009, 27(15):2457-2465.
92. Suenaga M., Fuse N., Yamaguchi T., et al. Pharmacokinetics, safety, and efficacy of FOLFIRI plus bevacizumab in Japanese colorectal cancer patients with UGT1A1 gene polymorphisms. JClin Pharmacol 2014, 54(5):495-502.
93. Braun M.S., Richman S.D., Quirke P., et al. Predictive biomarkers of chemotherapy efficacy in colorectal cancer: results from the UK MRC FOCUS trial. JClin Oncol 2008, 26(16):2690-2698.
94. Nygard S.B., Christensen I.J., Nielsen S.L., et al. Assessment of the topoisomerase I gene copy number as a predictive biomarker of objective response to irinotecan in metastatic colorectal cancer. Scand J Gastroenterol 2014, 49(1):84-91.
95. Moreira M.C., Barbot C., Tachi N., et al. The gene mutated in ataxia-ocular apraxia 1 encodes the new HIT/Zn-finger protein aprataxin. Nat Genet 2001, 29(2):189-193.
96. Dopeso H., Mateo-Lozano S., Elez E., et al. Aprataxin tumor levels predict response of colorectal cancer patients to irinotecan-based treatment. Clin Cancer Res 2010, 16(8):2375-2382.