Обоснование использования экспрессионных маркёров для персонализации химиотерапии рака лёгкого
Аннотация
Результаты хирургического лечения рака лёгкого в II-III стадии остаются неудовлетворительными, а используемая химиотерапия не даёт существенного прироста показателя выживаемости больных. Основным препятствием является недостаточно эффективный подбор химиопрепаратов и тактики лечения конкретного больного, основанный только на использовании стандартных клинических параметров. Существенная роль в формировании устойчивости опухоли лёгкого к назначаемым химиопрепаратам отводится генам монорезистентности, которые определяют резистентность/чувствительность опухолевых клеток к конкретным химиопрепаратам. В представленном обзоре рассмотрены механизмы транспорта, активации и мишени химиопрепаратов, определяются основные маркёры для прогнозирования их эффективности, а также возможность их применения в клинической практике. Для рака лёгкого охарактеризованы такие гены монорезистентности, как АВСС5, RRM1, ERCC1, TOP1, TOP2a, TUBB3 и TYMS. Приведены результаты клинических исследований, доказывающие эффективность их использования в качестве предиктивных маркёров для назначения отдельных химиопрепаратов. Манифестируется проспективное исследование авторов статьи с персонализированным назначением адъювантной химиотерапии больным раком лёгкого.
Об авторах
М. М. Цыганов
Томский НИИ онкологии; Национальный исследовательский Томский государственный университет
Россия
Россия
Е. О. Родионов
Томский НИИ онкологии
Россия
Россия
С. В. Миллер
Томский НИИ онкологии
Россия
Россия
Н. В. Литвяков
Томский НИИ онкологии; Национальный исследовательский Томский государственный университет
Россия
Россия
Список литературы
1. Scagliotti G.V., Pastorino U., Vansteenkiste J.F., Spaggiari L., Facciolo F., Orlowski T.M., Maiorino L., Hetzel M., Leschinger M., Visseren-Grul C. Randomized phase III study of surgery alone or surgery plus preoperative cisplatin and gemcitabine in stages IB to IIIA non-small-cell lung cancer. J Clin Oncol 2012; 30: 2: 172-178.
2. Vansteenkiste J., De Ruysscher D., Eberhardt W., Lim E., Senan S., Felip E., Peters S. Early and locally advanced non-small-cell lung cancer (NSCLC): ESMO Clinical Practice Guidelines for Diagnosis, Treatment and Follow-Up. Ann Oncol 2013; 241.
3. Depierre A., Westeel V., Jacoulet P. Preoperative chemotherapy for nonsmall cell lung cancer. Cancer Treat Rev 2001; 27: 2: 119-127.
4. Felip E., Massuti B., Alonso G., González-Larriba J., Camps C., Isla D., Costas E., Sanchez J., Griesinger F., Rosell R. Surgery (S) alone, preoperative (preop) paclitaxel/carboplatin (PC) chemotherapy followed by S, or S followed by adjuvant (adj) PC chemotherapy in early-stage nonsmall cell lung cancer (NSCLC): Results of the NATCH multicenter, randomized phase III trial. J Clin Oncol 2009; 27: 7500.
5. Lan J., Huang H.-Y., Lee S.-W., Chen T.-J., Tai H.-C., Hsu H.-P., Chang K.-Y., Li C.-F. TOP2A overexpression as a poor prognostic factor in patients with nasopharyngeal carcinoma. Tum Biol 2014; 35: 1: 179-187.
6. Wei C.H., Gorgan T.R., Elashoff D.A., Hines O.J., Farrell J.J., Donahue T.R. A meta-analysis of gemcitabine biomarkers in patients with pancreatico-biliary cancers. Pancreas 2013; 42: 8.
7. Shatokhina S.N., Zakharova N.M., Dedova M.G., Sambulov V.I., Shabalin V.N. Morphological marker of tumor progression in laryngeal cancer. Voprosy onkologii 2013; 59: 2: 66-70.
8. Fung K.L., Tepede A.K, Pluchino K.M., Pouliot L.M., Pixley J.N., Hall M.D., Gottesman M.M. Uptake of compounds that selectively kill multidrug-resistant cells: the copper transporter SLC31A1 (CTR1) increases cellular accumulation of the thiosemicarbazone NSC73306. Mol Pharmaceut 2014; 11: 8: 2692-2702.
9. Li J., Li Z.N., Du Y.J., Li X.Q., Bao Q.L., Chen P. Expression of MRP1, BCRP, LRP, and ERCC1 in advanced non-small-cell lung cancer: correlation with response to chemotherapy and survival. Clin Lung Cancer 2009; 10: 6: 414-421.
10. Kalikaki A., Voutsina A., Koutsopoulos A., Papadaki C., Sfakianaki M., Yachnakis E., Xyrafas A., Kotsakis A., Agelaki S., Souglakos J. ERCC1 SNPs as potential predictive biomarkers in non-small cell lung cancer patients treated with platinum-based chemotherapy. Cancer Investigat 2015.
11. De Dosso S., Zanellato E., Nucifora M., Boldorini R., Sonzogni A., Biffi R., Fazio N., Bucci E., Beretta O., Crippa S. ERCC1 predicts outcome in patients with gastric cancer treated with adjuvant cisplatin-based chemotherapy. Cancer Chemother Pharmacol 2013; 72: 1: 159-165.
12. Park K.W., Jung E.-S., Kim D.-G., Yoo Y.-K., Hong T.-H., Lee I.S., Koh Y.H., Kim J.-H., Lee M.A. ERCC1 can be a prognostic factor in hilar cholangiocarcinoma and extrahepatic bile duct cancer, but not in intra-hepatic cholangiocarcinoma. Cancer Res Treat 2013; 45: 1: 63-69.
13. Yuanming L., Lineng Z., Baorong S., Junjie P., Sanjun C. BRCA1 and ERCC1 mRNA levels are associated with lymph node metastasis in Chinese patients with colorectal cancer. BMC Cancer 2013; 13: 1: 103.
14. Yan D., Wei P., An G., Chen W. Prognostic potential of ERCC1 protein expression and clinicopathologic factors in stage III/N2 non-small cell lung cancer. J Cardiothorac Surg 2013; 8: 149.
15. Tiseo M., Bordi P., Bortesi B., Boni L., Boni C., Baldini E., Grossi F., Recchia F., Zanelli F., Fontanini G. ERCC1/BRCA1 expression and gene polymorphisms as prognostic and predictive factors in advanced NSCLC treated with or without cisplatin. Brit J Cancer 2013; 108: 8: 1695-1703.
16. Han Y., Wang X.-B., Xiao N., Liu Z.-D. mRNA expression and clinical significance of ERCC1, BRCA1, RRM1, TYMS and TUBB3 in postoperative patients with non-small cell lung cancer. Asian Pac J Cancer Prev 2013; 14: 5: 2987-2990.
17. Bepler G., Williams C., Schell M.J., Chen W., Zheng Z., Simon G., Gadgeel S., Zhao X., Schreiber F., Brahmer J. Randomized international phase III trial of ERCC1 and RRM1 expression-based chemotherapy versus gemcitabine/carboplatin in advanced non-small-cell lung Cancer. J Clin Oncol 2013; JCO. 2012.46. 9783.
18. Olaussen K.A., Dunant A., Fouret P., Brambilla E., Andre F., Haddad V., Taranchon E., Filipits M., Pirker R., Popper H.H. DNA repair by ERCC1 in non-small-cell lung cancer and cisplatin-based adjuvant chemotherapy. New England J Med 2006; 355: 10: 983-991.
19. Kaira K., Takahashi T., Murakami H., Shukuya T., Kenmotsu H., Ono A., Naito T., Tsuya A., Nakamura Y., and Endo M. The role of ßIII-tubulin in non-small cell lung cancer patients treated by taxane-based chemotherapy. Intern J Clin Oncol 2013; 18: 3: 371-379.
20. Leng X.-F., Chen M.-W, Xian L., Dai L., Ma G.-Y., Li M.-H. Combined analysis of mRNA expression of ERCC1, BAG-1, BRCA1, RRM1 and TUBB3 to predict prognosis in patients with non-small cell lung cancer who received adjuvant chemotherapy. J Exp Clin Cancer Res 2012; 31: 1: 25.
21. Reiman T., Lai R., Veillard A., Paris E., Soria J., Rosell R., Taron M., Graziano S., Kratzke R., Seymour L. Cross-validation study of class III beta-tubulin as a predictive marker for benefit from adjuvant chemotherapy in resected non-small-cell lung cancer: analysis of four randomized trials. Ann Oncol 2011; 33.
22. Levallet G., Bergot E., Antoine M., Creveuil C., Santos A.O., Beau-Faller M., De Fraipont F., Brambilla E., Levallet J., Morin F. High TUBB3 expression, an independent prognostic marker in patients with early non-small cell lung cancer treated by preoperative chemotherapy, is regulated by K-Ras signaling pathway. Mol Cancer Therapeut. 2012; 11: 5: 1203-1213.
23. Jakobsen J.N., Santoni-Rugiu E., Sorensen J.B. Use of TUBB3 for patient stratification and prognosis in lung cancer. Lung Cancer 2015; 4: 2: 97-110.
24. Ritzel M.W., Ng A.M., Yao S.Y., Graham K., Loewen S.K., Smith K.M., Ritzel R.G., Mowles D.A., Carpenter P., Chen X.-Z. Molecular identification and characterization of novel human and mouse concentrative Na+-nucleoside cotransporter proteins (hCNT3 and mCNT3) broadly selective for purine and pyrimidine nucleosides (system cib). J Biol Chem. 2001; 276: 4: 2914-2927.
25. Oguri T., Achiwa H., Sato S., Bessho Y., Takano Y., Miyazaki M., Muramatsu H., Maeda H., Niimi T., Ueda R. The determinants of sensitivity and acquired resistance to gemcitabine differ in non-small cell lung cancer: a role of ABCC5 in gemcitabine sensitivity. Mol Cancer Therapeut 2006; 5: 7: 1800-1806.
26. Heinemann V., Xu Y.-Z., Chubb S., Sen A., Hertel L.W., Grindey G.B., Plunkett W. Cellular elimination of 2’, 2’-difuorodeoxycytidine 5’-triphosphate: a mechanism of self-potentiation. Cancer Res 1992; 52: 3: 533-539.
27. Plunkett W., Huang P., Xu Y.-Z., Heinemann V., Grunewald R., Gandhi V. Gemcitabine: metabolism, mechanisms of action, and self-potentiation. in Seminars in oncology. 1995.
28. Liu Z.-Q., Han Y.-C., Zhang X., Chu L., Fang J.-M., Zhao H.-X., Chen Y.-J., Xu Q. Prognostic value of human equilibrative nucleoside transporter in pancreatic cancer receiving gemcitabin-based chemotherapy: a meta-analysis. PLoS One. 2014; 9: 1: 87-103.
29. Farrell J.J., Elsaleh H., Garcia M., Lai R., Ammar A., Regine W.F., Abrams R., Benson A.B., Macdonald J., Cass C.E. Human equilibrative nucleoside transporter levels predict response to gemcitabine in patients with pancreatic cancer. Gastroenterology 2009; 136: 1: 187-195.
30. Ward J.L., Sherali A., Mo Z.-P., Tse C.-M. Kinetic and pharmacological properties of cloned human equilibrative nucleoside transporters, ENT1 and ENT2, stably expressed in nucleoside transporter-deficient PK15 cells ENT2 exhibits a low affinity for guanosine and cytidine but a high affinity for inosine. J Biol Chem 2000; 275: 12: 8375-8381.
31. Hagmann W., Jesnowski R., Faissner R., Guo C., Löhr J.M. ATP-binding cassette C transporters in human pancreatic carcinoma cell lines: upregulation in 5-fluorouracil-resistant cells. Pancreatology 2009; 9: 1: 136-144.
32. 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.
33. Yu Y., Ding S., Liang Y., Zheng Y., Li W., Yang L., Zheng X., Jiang J. Expression of ERCC1, TYMS, TUBB3, RRM1 and TOP2A in patients with esophageal squamous cell carcinoma: A hierarchical clustering analysis. Exper Ther Med 2014; 7: 6: 1578-1582.
34. Aoki Y., Sakogawa K., Hihara J., Emi M., Hamai Y., Kono K., Shi L., Sun J., Kitao H., Ikura T. Involvement of ribonucleotide reductase-M1 in 5-fluorouracil-induced DNA damage in esophageal cancer cell lines. Intern J Oncol 2013; 42: 6: 1951-1960.
35. Trahtenberg A.H., Kolbanov K.I. Lung cancer. Atmosphere Pulmonol Allergol 2008; 4: 3-9.
36. Chissov V.I., Dar'jalova S.L. Oncology (clinical guidelines). М.: Gjeotar-Media; 2006; 638.
37. Kim B., Fatayer H., Hanby A.M., Horgan K., Perry S.L., Valleley E.M., Verghese E.T., Williams B.J., Thorne J.L., Hughes TA. Neoadjuvant chemotherapy induces expression levels of breast cancer resistance protein that predict disease-free survival in breast cancer. PLoS One. 2013; 8: 5: 627-666.
38. Iusuf D., Teunissen S.F., Wagenaar E., Rosing H., Beijnen J.H., and Schinkel A.H. P-glycoprotein (ABCB1) transports the primary active tamoxifen metabolites endoxifen and 4-hydroxytamoxifen and restricts their brain penetration. J Pharmacol Exper Ther 2011; 337: 3: 710-717.
39. Ieiri I. Functional significance of genetic polymorphisms in P-glycoprotein (MDR1, ABCB1) and breast cancer resistance protein (BCRP, ABCG2). Drug Metab Pharmacokinet 2012; 27: 1: 85-105.
40. Buenoв R., Farber D., D'ami T.A., Demmyâ M., Steven J., Feigenbergä M., Frederic W., and Krisâ G. Non-small cell lung cancer. Recom Diagn Treat Lung Cancer. 2006; 2: 42-70.
41. Litman T., Druley T., Stein W., Bates S. From MDR to MXR: new understanding of multidrug resistance systems, their properties and clinical significance. Cellul Mol Life Scien CMLS. 2001; 58: 7: 931-959.
42. Leith C.P., Kopecky K.J., Chen I.-M., Eijdems L., Slovak M.L., Mcconnell T.S., Head D.R., Weick J., Grever M.R., Appelbaum F.R. Frequency and clinical significance of the expression of the multidrug resistance proteins MDR1/P-glycoprotein, MRP1, and LRP in acute myeloid leukemia. A Southwest Oncology Group Study Blood 1999; 94: 3: 1086-1099.
43. Amiri-Kordestani L., Basseville A., Kurdziel K., Fojo A.T., Bates S.E. Targeting MDR in breast and lung cancer: discriminating its potential importance from the failure of drug resistance reversal studies. Drug Res Updates 2012; 15: 1: 50-61.
44. Tang S.C., Lankheet N.A., Poller B., Wagenaar E., Beijnen J.H., Schinkel A.H. P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2) restrict brain accumulation of the active sunitinib metabolite N-desethyl sunitinib. Journal of Pharmacology and Experimental Therapeutics. 2012; 341: 1: 164-173.
45. Tsurutani J., Nitta T., Hirashima T., Komiya T., Uejima H., Tada H., Syunichi N., Tohda A., Fukuoka M., Nakagawa K. Point mutations in the topoisomerase I gene in patients with non-small cell lung cancer treated with irinotecan. Lung Cancer 2002; 35: 3: 299-304.
46. Kanzawa F., Sugimoto Y., Minato K., Kasahara K., Bungo M., Nakagawa K., Fujiwara Y., Liu L.F., Saijo N. Establishment of a camptothecin analogue (CPT-11)-resistant cell line of human non-small cell lung cancer: characterization and mechanism of resistance. Cancer Res 1990; 50: 18: 5919-5924.
47. Nygârd S.B., Christensen I.J., Nielsen S.L., Nielsen H.J., Brünner N., Spindler K.-L.G. Assessment of the topoisomerase I gene copy number as a predictive biomarker of objective response to irinotecan in metastatic colorectal cancer. Scand J Gastroenterol 2013; 49: 1: 84-91.
48. Kümler I., Balslev E., Stenvang J., Brünner N., Nielsen D. A phase II study of weekly irinotecan in patients with locally advanced or metastatic HER2-negative breast cancer and increased copy numbers of the topoi-somerase 1 (TOP1) gene: a study protocol. BMC Cancer 2015; 15: 1: 78.
49. Grunnet M., Calatayud D., Schultz N.A., Hasselby J.P., Mau-Sөrensen M., Brünner N., Stenvang J. TOP1 gene copy numbers are increased in cancers of the bile duct and pancreas. Scand J Gastroenterol 2015; 0: 1-10.
50. Vulsteke C., Lambrechts D., Dieudonné A., Hatse S., Brouwers B., Van Brussel T., Neven P., Belmans A., Schöffski P., Paridaens R. Genetic variability in the multidrug resistance associated protein-1 (ABCC1/MRP1) predicts hematological toxicity in breast cancer patients receiving (neo-) adjuvant chemotherapy with 5-fluorouracil, epirubicin and cyclophosphamide (FEC). Ann Oncol 2013; 24: 6: 1513-1525.
51. Lacave R., Coulet F., Ricci S., Touboul E., Flahault A., Rateau J., Cesari D., Lefranc J., Bernaudin J. Comparative evaluation by semiquantitative reverse transcriptase polymerase chain reaction of MDR1, MRP and GSTp gene expression in breast carcinomas. Brit J Cancer 1998; 77: 5: 694.
52. Korman D.B. Fundamentals of anticancer chemotherapy. М.: Practical medicine; 2006; 512.
53. Leivonen S.-K., Rokka A., Östling P., Kohonen P., Corthals G.L., Kallioniemi O., Perälä M. Identification of miR-193b targets in breast cancer cells and systems biological analysis of their functional impact. Mol Cell Prot 2011; 10: 7: 110.
54. Litviakov N.V., Garbukov E.Yu., Slonimskaya E.M., Tsyganov M.M., Denisov E.V., Vtorushin S.V., Christenko K.Yu., Zavyalova M.V., Cherdyntseva N.V. Correlation of metastasis-free survival in breast cancer patients and an expression vector of multidrug resistance genes in tumor during neoadjuvant chemotherapy. Voprosy Onkologii. 2013; 3: 59: 334-340.
55. Litviakov N.V. Gradient phenomenon of multidrug resistance gene expression in breast cancer. Siber J Oncol 2013; 4: 58: 5-11.
56. Abuhammad S., Zihlif M. Gene expression alterations in doxorubicin resistant MCF7 breast cancer cell line. Genomics 2013; 101: 4: 213-220.
57. Durbecq V., Paesmans M., Cardoso F., Desmedt C., Di Leo A., Chan S., Friedrichs K., Pinter T., Van Belle S., Murray E. Topoisomerase-II-expression as a predictive marker in a population of advanced breast cancer patients randomly treated either with single-agent doxorubicin or single-agent docetaxel. Mol Cancer Ther 2004; 3: 10: 1207-1214.
58. Orlando L., Del Curto B., Gandini S., Ghisini R., Pietri E., Torrisi R., Balduzzi A., Cardillo A., Dellapasqua S., Veronesi P. Topoisomerase II-gene status and prediction of pathological complete remission after anthracycline-based neoadjuvant chemotherapy in endocrine non-responsive Her2/neu-positive breast cancer. The Breast 2008; 17: 5: 506-511.
59. Miyoshi Y., Kurosumi M., Kurebayashi J., Matsuura N., Takahashi M., Tokunaga E., Egawa C., Masuda N., Kono S., Morimoto K. Predictive factors for anthracycline-based chemotherapy for human breast cancer. Breast Cancer 2010; 17: 2: 103-109.
60. Kawachi K., Sasaki T., Murakami A., Ishikawa T., Kito A., Ota I., Shimizu D., Nozawa A., Nagashima Y., Machinami R. The topoisomerase II alpha gene status in primary breast cancer is a predictive marker of the response to anthracycline-based neoadjuvant chemotherapy. Pathol-Res Pract 2010; 206: 3: 156-162.
Для цитирования:
Цыганов М.М., Родионов Е.О., Миллер С.В., Литвяков Н.В. Обоснование использования экспрессионных маркёров для персонализации химиотерапии рака лёгкого. Антибиотики и Химиотерапия. 2015;60(9-10):38-45.
For citation:
Tsyganov M.M., Rodionov E.O., Miller S.V., Litvyakov N.V. Substantiation of Expressive Markers Use to Personalize Lung Cancer Chemotherapy. Antibiotics and Chemotherapy. 2015;60(9-10):38-45. (In Russ.)
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