진행성 비소세포폐암에서 KRAS와 Tau의 항암 치료에 대한 반응의 예측 인자로서의 의의
Predictive Significance of KRAS and Tau for Chemoresponse in Advanced Non-Small-Cell Lung Cancer
2
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Background : Taxane-platinum combinations are often used as first-line treatments for patients with advanced non-small cell lung cancer (NSCLC). Response to chemotherapy for these patients is still poor. The aim of our study was to investigate, for this disease, whether KRAS and Tau proteins affect responses to taxane-platinum combinations. Methods : Expression of KRAS and Tau was examined immunohistochemically in 71 tumor samples obtained from patients with stage ⅢB or Ⅳ NSCLC prior to combination therapy. Expression was correlated with tumor responses. Results : The response rate was 55% (39 of 71). KRAS and Tau were expressed in seven (10%) and 31 (44%) patients, respectively. All seven KRAS-positive patients were non-responders (p=0.014). Among Tau-positive patients , 35% (11 of 31) responded to therapy, whereas a partial response was observed in 70% (28 of 40) of Tau-negatives (p= 0.045). Two were positive for both, and they were non-responders. In patients negative for both, the response rate was 71% (25 of 35) (p=0.012). Conclusions : Expression of KRAS and Tau are significantly correlated with poor responses to this combination therapy in advanced NSCLC patients, and may be a useful marker for chemoresistance.
Abstract
Background : Taxane-platinum combinations are often used as first-line treatments for patients with advanced non-small cell lung cancer (NSCLC). Response to chemotherapy for these patients is still poor. The aim of our study was to investigate, for this disease, whether KRAS and Tau proteins affect responses to taxane-platinum combinations. Methods : Expression of KRAS and Tau was examined immunohistochemically in 71 tumor samples obtained from patients with stage ⅢB or Ⅳ NSCLC prior to combination therapy. Expression was correlated with tumor responses. Results : The response rate was 55% (39 of 71). KRAS and Tau were expressed in seven (10%) and 31 (44%) patients, respectively. All seven KRAS-positive patients were non-responders (p=0.014). Among Tau-positive patients , 35% (11 of 31) responded to therapy, whereas a partial response was observed in 70% (28 of 40) of Tau-negatives (p= 0.045). Two were positive for both, and they were non-responders. In patients negative for both, the response rate was 71% (25 of 35) (p=0.012). Conclusions : Expression of KRAS and Tau are significantly correlated with poor responses to this combination therapy in advanced NSCLC patients, and may be a useful marker for chemoresistance.
참고문헌 (28)
- "The cause of death statistics"[URL]
- Scientific Committee of Korean Association of Tuberculosis and Respiratory Disease, "The national survey of lung cancer in Korea", Tuberc Respir Dis, 46, pp.455~465 (1999)
- Rigas JR, "Taxane-platinum combinations in advanced non-small cell lung cancer: a review", Oncologist, 9(2), pp.16~23 (2004)
- Chu Q, "Taxanes as firstline therapy for advanced non-small cell lung cancer: a systematic review and practice guideline", Lung Cancer, 50, pp.355~374 (2005)
- Pirker R, "Paclitaxel", cisplatin in advanced non-small-cell lung cancer (NSCLC), 1995, pp.6, 833~835
- The American Society of Clinical Oncology, "Clinical practice guidelines for the treatment of unresectable non-small-cell lung cancer", J Clin Oncol, 15, pp.2996~3018 (1997)
- Riely GJ, "KRAS mutations in non-small cell lung cancer", Proc Am Thorac Soc, pp.201~205 (2009)
- Messina S, "Ras inhibition amplifies cisplatin sensitivity of human glioblastoma", Biochem Biophys Res Commun, 320, pp.493~500 (2004)
- Wagner P, "Microtubule Associated Protein (MAP)-Tau: a novel mediator of paclitaxel sensitivity in vitro and in vivo", Cell Cycle, 4, pp.1149~1152 (2005)
- Tanaka S, "Tau expression and efficacy of paclitaxel treatment in metastatic breast cancer", Cancer Chemother Pharmacol, 64, pp.341~346 (2009)
- Mimori K, "Reduced tau expression in gastric cancer can identify candidates for successful Paclitaxel treatment", Br J Cancer, 94, pp.1894~1897 (2006)
- Sobin LH, "TNM Classification of Malignant Tumors, fifth edition (1997): Union Internationale Contre le Cancer and the American Joint Committee on Cancer", Cancer, 80, pp.1803~1804 (1997)
- Therasse P, "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, pp.205~216 (2000)
- Kang YH, "The relationship between microvessel count and the expression of vascular endothelial growth factor, p53, and K-ras in non-small cell lung cancer", J Korean Med Sci, 16, pp.417~423 (2001)
- Rouzier R, "Microtubule-associated protein tau: a marker of paclitaxel sensitivity in breast cancer", Proc Natl Acad Sci, pp.8315~8320 (2005)
- Harada M, "Prognostic significance of the expression of ras oncogene product in non-small cell lung cancer", Cancer, 69, pp.72~77 (1992)
- Kosaka T, "Mutations of the epidermal growth factor receptor gene in lung cancer: biological and clinical implications", Cancer Res, 64, pp.8919~8923 (2004)
- Cvetkovic G, "K-ras mutation predictive significance in platinum based chemotherapeutic protocols in patients with advanced non-small cell lung cancer", Vojnosanit Pregl, 66, pp.149~155 (2009)
- Massarelli E, "KRAS mutation is an important predictor of resistance to therapy with epidermal growth factor receptor tyrosine kinase inhibitors in non-small-cell lung cancer", Clin Cancer Res, 13, pp.2890~3289 (2007)
- Guha U, "Comparisons of tyrosine phosphorylated proteins in cells expressing lung cancer-specific alleles of EGFR and KRAS", Proc Natl Acad Sci, pp.14112~14117 (2008)
- Pao W, "KRAS mutations and primary resistance of lung adenocarcinomas to gefitinib or erlotinib", PLoS Med, 2, pp.e17~ (2005)
- Lievre A, "KRAS mutations as an independent prognostic factor in patients with advanced colorectal cancer treated with cetuximab", J Clin Oncol, 26, pp.374~379 (2008)
- Dumontet C, "Expression of class III beta tubulin in non-small cell lung cancer is correlated with resistance to taxane chemotherapy", Bull Cancer, 92, pp.E25~E30 (2005)
- Horwitz SB, "Taxol:mechanisms of action and resistance", J Natl Cancer Inst Monogr, pp.55~61 (1993)
- Orr GA, "Mechanisms of Taxol resistance related to microtubules", Oncogene, 22, pp.7280~7295 (2003)
- Monzo M, "Paclitaxel resistance in nonsmall-cell lung cancer associated with beta-tubulin gene mutations", J Clin Oncol, 17, pp.1786~1793 (1999)
- Seve P, "Is class III beta-tubulin a predictive factor in patients receiving tubulin-binding agents?", Lancet Oncol, 9, pp.168~175 (2008)
- Verdier-Pinard P, "Analysis of tubulin isotypes and mutations from taxol-resistant cells by combined isoelectrofocusing and mass spectrometry", Biochemistry, 42, pp.5349~5357 (2003)