Abstract
Background
Currently, first-line chemotherapy in advanced colorectal cancer is not tailored on predictive biomarkers. Bax proapoptotic protein may correlate to chemosensitivity and differential response to irinotecan or oxaliplatin-based combinations.
Methods
Bax expression was assessed by immunohistochemistry in 49 advanced colorectal cancer patients enrolled at our institution from 2002 to 2004 within a multicenter, phase II, randomized trial of first-line UFT/leucovorin/irinotecan (TEGAFIRI) versus UFT/leucovorin/oxaliplatin (TEGAFOX).
Results
Bax-positive and negative samples were 49 and 51 %. Response was significantly lower in Bax positive (25 %) as compared to Bax negative (56 %) (Odds ratio = 0.26; p = 0.03). No significant difference was noted in TEGAFOX subgroup; in TEGAFIRI arm, responses were lower in Bax positive (18 %) than Bax negative (67 %) (Odds ratio = 0.11; p = 0.03). No difference in terms of progression-free and overall survival was observed according to Bax.
Conclusion
Bax-negative colorectal cancer may identify a specific phenotype of patients with significantly higher chance to respond to doublet irinotecan-based chemotherapy.
References
Jemal A, Siegel R, Ward E et al (2009) Cancer statistics. CA Cancer J Clin 59:225–249
Dienstmann R, Markman B, Tabernero J (2012) Application of monoclonal antibodies as cancer therapy in solid tumors. Curr Clin Pharmacol 7:137–145
De Roock W, Claes B, Bernasconi D et al (2010) Effect of KRAS, BRAF, NRAS, and PI3KCA mutations on the efficacy of cetuximab plus chemotherapy in chemotherapy-refractory metastatic colorectal cancer: a retrospective consortium analysis. Lancet Oncol 11:753–762
Perrone F, Lampis A, Orsenigo M et al (2009) PI3KCA/PTEN deregulation contributes to impaired responses to cetuximab in metastatic colorectal cancer patients. Ann Oncol 20:84–90
Miyashita T, Reed JC (1995) Tumor suppressor p53 is a direct transcriptional activator of the human bax gene. Cell 80:293–299
Jeong SH, Han JH, Kim JH et al (2011) Bax predicts outcome in gastric cancer patients treated with 5-fluorouracil, leucovorin, and oxaliplatin palliative chemotherapy. Dig Dis Sci 56:131–138
Krajewski S, Blomqvist C, Franssila K et al (1995) Reduced expression of proapoptotic gene BAX is associated with poor response rates to combination chemotherapy and shorter survival in women with metastatic breast adenocarcinoma. Cancer Res 55:4471–4478
Kupryjanczyk J, Szymanska T, Madry R et al (2003) Evaluation of clinical significance of TP53, BCL-2, BAX and MEK1 expression in 229 ovarian carcinomas treated with platinum-based regimen. Br J Cancer 88:848–854
Bajetta E, Di Bartolomeo M, Buzzoni R et al (2007) Uracil/ftorafur/leucovorin combined with irinotecan (TEGAFIRI) or oxaliplatin (TEGAFOX) as first-line treatment for metastatic colorectal cancer patients: results of a randomised phase II study. Br J Cancer 96:439–444
Therasse P, Arbuck SG, Eisenhauer EA et al (2000) New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst 92:205–216
Pietrantonio F, Biondani P, de Braud F et al (2012) Bax expression is predictive of favorable clinical outcome in chemonaive advanced gastric cancer patients treated with capecitabine, oxaliplatin, and irinotecan regimen. Transl Oncol 5:155–159
Siena S, Sartore-Bianchi A, Di Nicolantonio F et al (2009) Biomarkers predicting clinical outcome of epidermal growth factor receptor-targeted therapy in metastatic colorectal cancer. J Natl Cancer Inst 101:1308–1324
Sinicrope FA, Sargent DJ (2012) Molecular pathways: microsatellite instability in colorectal cancer: prognostic, predictive, and therapeutic implications. Clin Cancer Res 18:1506–1512
McDonald AC, Brown R (1998) Induction of p53-dependent and p53-independent cellular responses by topoisomerase 1 inhibitors. Br J Cancer 78:745–751
Nehls O, Okech T, Hsieh CJ et al (2007) Studies on p53, BAX and Bcl-2 protein expression and microsatellite instability in stage III (UICC) colon cancer treated by adjuvant chemotherapy: major prognostic impact of proapoptotic BAX. Br J Cancer 96:1409–1418
Katkoori VR, Suarez-Cuervo C, Shanmugam C et al (2010) Bax expression is a candidate prognostic and predictive marker of colorectal cancer. J Gastrointest Oncol 1:76–89
Paradiso A, Simone G, Lena MD et al (2001) Expression of apoptosis-related markers and clinical outcome in patients with advanced colorectal cancer. Br J Cancer 84:651–658
Yee KS, Wilkinson S, James J et al (2009) PUMA- and Bax-induced autophagy contributes to apoptosis. Cell Death Differ 16:1135–1145
Fallik D, Borrini F, Boige V et al (2003) Microsatellite instability is a predictive factor of the tumor response to irinotecan in patients with advanced colorectal cancer. Cancer Res 63:5738–5744
Bras-Goncalves RA, Rosty C, Laurent-Puig P et al (2000) Sensitivity to CPT-11 of xenografted human colorectal cancers as a function of microsatellite instability and p53 status. Br J Cancer 82:913–923
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Pietrantonio, F., Biondani, P., Milione, M. et al. Lack of Bax expression is associated with irinotecan-based treatment activity in advanced colorectal cancer patients. Clin Transl Oncol 15, 582–586 (2013). https://doi.org/10.1007/s12094-012-0971-3
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DOI: https://doi.org/10.1007/s12094-012-0971-3