Journal of Shanghai Jiao Tong University (Medical Science) >

2022 , Vol. 42 >Issue 1: 82 - 89

DOI: https://doi.org/10.3969/j.issn.1674-8115.2022.01.012

Clinical research

Application of high-throughput drug sensitivity screening system in the treatment of non-small cell lung cancer with malignant pleural effusion

  • Yu ZHANG ,
  • Xiaoyuan WU ,
  • Lihua GUAN ,
  • Yiyuan LIU ,
  • Xingyue PENG ,
  • Haiyan XIE ,
  • Wei HU ,
  • Keke HAO ,
  • Ning XIA ,
  • Guojun LU ,
  • Zhibo HOU
Expand
  • 1.Department of Respiratory Medicine, Nanjing Chest Hospital, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing 210029, China
    2.Central laboratory, Nanjing Chest Hospital, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing 210029, China
    3.Information Department, Nanjing Chest Hospital, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing 210029, China
    4.Nanjing TechBoon Clinical Medicine Institute, Nanjing 210018, China
ZHANG Yu, E-mail: zhangyu2113_nj@163.com.

Received date: 2021-08-04

  Online published: 2022-01-28

Supported by

General Program of Medical Scientific Research Project of Jiangsu Health and Family Planning Commission(H2018030)

Fold

Abstract

Objective

·To explore the feasibility of individualized treatment of malignant pleural effusion (MPE) patients with non-small cell lung cancer (NSCLC) guided by in vitro high-throughput drug sensitivity screening system.

Methods

·Thirty NSCLC patients with MPE treated in Nanjing Chest Hospital from January 2019 to May 2020 were included. The tumor cells in MPE were collected and isolated, and primary cells were cultured. The ex vivo drug sensitivity of primary cells was assessed for 30 chemotherapeutical and molecular targeted drugs by using the high-throughput drug sensitivity screening system of automated digital fluorescence imager. The consistency between the drug sensitivity assay results and the clinical efficacy of patients was evaluated.

Results

·The ex vivo drug sensitivity results of primary tumor cells cultured from MPE revealed considerable heterogeneity in drug response. Most of the primary cells were sensitive to Epirubicin, Lobaplatin, Gemcitabine and Irinotecan. Clinical efficacy of 23 patients can be evaluated. For patients with previously untreated, epidermal growth factor receptor (EGFR) mutation-positive advanced NSCLC, the consistency between the efficacy of targeted therapy and the high-throughput drug sensitivity assay results was 44.4% (4/9). For the EGFR negative untreated patients and EGFR mutation-positive advanced NSCLC patients with acquired resistance to targeted treatment, the consistency between the therapeutic effect of chemotherapy and the high-throughput drug sensitivity assay results was 85.7% (12/14).

Conclusion

·The high-throughput drug sensitivity assay based on MPE primary cell culture in NSCLC patients has a high consistency with the clinical efficacy of chemotherapy, which is helpful for decision-making of personalized chemotherapy.

Key words： non-small cell lung cancer; pleural effusion; in vitro chemosensitivity assay; individualized treatment

Cite this article

Yu ZHANG , Xiaoyuan WU , Lihua GUAN , Yiyuan LIU , Xingyue PENG , Haiyan XIE , Wei HU , Keke HAO , Ning XIA , Guojun LU , Zhibo HOU . Application of high-throughput drug sensitivity screening system in the treatment of non-small cell lung cancer with malignant pleural effusion[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2022 , 42(1) : 82 -89 . DOI: 10.3969/j.issn.1674-8115.2022.01.012

References

1 BRAY F, FERLAY J, SOERJOMATARAM I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2018, 68(6): 394-424.
2 SIEGEL R L, MILLER K D, JEMAL A. Cancer statistics, 2018[J]. CA Cancer J Clin, 2018, 68(1): 7-30.
3 BURROWS C M, MATHEWS W C, COLT H G. Predicting survival in patients with recurrent symptomatic malignant pleural effusions: an assessment of the prognostic values of physiologic, morphologic, and quality of life measures of extent of disease[J]. Chest, 2000, 117(1): 73-78.
4 CUFER T, KNEZ L. Update on systemic therapy of advanced non-small-cell lung cancer[J]. Expert Rev Anticancer Ther, 2014, 14(10): 1189-1203.
5 SZULKIN A, OTV?S R, HILLERDAL C O, et al. Characterization and drug sensitivity profiling of primary malignant mesothelioma cells from pleural effusions[J]. BMC Cancer, 2014, 14: 709.
6 ?TV?S R, SZULKIN A, HILLERDAL C O, et al. Drug sensitivity profiling and molecular characteristics of cells from pleural effusions of patients with lung adenocarcinoma[J]. Genes Cancer, 2015, 6(3/4): 119-128.
7 中国临床肿瘤学会指南工作委员会组织. 中国临床肿瘤学会(CSCO)原发性肺癌诊疗指南-2019[M]. 北京: 人民卫生出版社, 2019.
8 LEE S H. Chemotherapy for lung cancer in the era of personalized medicine[J]. Tuberc Respir Dis (Seoul), 2019, 82(3): 179-189.
9 FRIBOULET L, OLAUSSEN K A, PIGNON J P, et al. ERCC1 isoform expression and DNA repair in non-small-cell lung cancer[J]. N Engl J Med, 2013, 368(12): 1101-1110.
10 OLAUSSEN K A, POSTEL-VINAY S. Predictors of chemotherapy efficacy in non-small-cell lung cancer: a challenging landscape[J]. Ann Oncol, 2016, 27(11): 2004-2016.
11 SEUFFERLEIN T, AHN J, KRNDIJA D, et al. Tumor biology and cancer therapy: an evolving relationship[J]. Cell Commun Signal, 2009, 7: 19.
12 BEN-DAVID U, SIRANOSIAN B, HA G, et al. Genetic and transcriptional evolution alters cancer cell line drug response[J]. Nature, 2018, 560(7718): 325-330.
13 JIN K T, TENG L S, SHEN Y P, et al. Patient-derived human tumour tissue xenografts in immunodeficient mice: a systematic review[J]. Clin Transl Oncol, 2010, 12(7): 473-480.
14 FULCHER M L, RANDELL S H. Human nasal and tracheo-bronchial respiratory epithelial cell culture[J]. Methods Mol Biol, 2013, 945: 109-121.
15 WILDING J L, BODMER W F. Cancer cell lines for drug discovery and development[J]. Cancer Res, 2014, 74(9): 2377-2384.
16 BYRNE A T, ALFéREZ D G, AMANT F, et al. Interrogating open issues in cancer precision medicine with patient-derived xenografts[J]. Nat Rev Cancer, 2017, 17(4): 254-268.
17 GAO H, KORN J M, FERRETTI S, et al. High-throughput screening using patient-derived tumor xenografts to predict clinical trial drug response[J]. Nat Med, 2015, 21(11): 1318-1325.
18 ROSSI G, MANFRIN A, LUTOLF M P. Progress and potential in organoid research[J]. Nat Rev Genet, 2018, 19(11): 671-687.
19 DE WETERING MVAN, FRANCIES H E, FRANCIS J M, et al. Prospective derivation of a living organoid biobank of colorectal cancer patients[J]. Cell, 2015, 161(4): 933-945.
20 CUNDERLíKOVá B. Issues to be considered when studying cancer in vitro[J]. Crit Rev Oncol Hematol, 2013, 85(2): 95-111.
21 YIN S Y, XI R B, WU A W, et al. Patient-derived tumor-like cell clusters for drug testing in cancer therapy[J]. Sci Transl Med, 2020, 12(549): eaaz1723.
22 MARKASZ L, KIS L L, STUBER G, et al. Hodgkin-lymphoma-derived cells show high sensitivity to dactinomycin and paclitaxel[J]. Leuk Lymphoma, 2007, 48(9): 1835-1845.
23 SKRIBEK H, OTVOS R, FLABERG E, et al. Chronic lymphoid leukemia cells are highly sensitive to the combination of prednisolone and daunorubicin, but much less to doxorubicin or epirubicin[J]. Exp Hematol, 2010, 38(12): 1219-1230.
24 DEDINSZKI D, KISS A, MáRKáSZ L, et al. Inhibition of protein phosphatase-1 and-2A decreases the chemosensitivity of leukemic cells to chemotherapeutic drugs[J]. Cell Signal, 2015, 27(2): 363-372.
25 MANCINI R, GIARNIERI E, DE VITIS C, et al. Spheres derived from lung adenocarcinoma pleural effusions: molecular characterization and tumor engraftment[J]. PLoS One, 2011, 6(7): e21320.
26 SZULKIN A, NILSONNE G, MUNDT F, et al. Variation in drug sensitivity of malignant mesothelioma cell lines with substantial effects of selenite and bortezomib, highlights need for individualized therapy[J]. PLoS One, 2013, 8(6): e65903.
27 ROSCILLI G, DE VITIS C, FERRARA F F, et al. Human lung adenocarcinoma cell cultures derived from malignant pleural effusions as model system to predict patients chemosensitivity[J]. J Transl Med, 2016, 14: 61.
28 ALIZADEH A A, ARANDA V, BARDELLI A, et al. Toward understanding and exploiting tumor heterogeneity[J]. Nat Med, 2015, 21(8): 846-853.
29 王丹. 高通量体外药敏检测技术在晚期肺癌伴恶性胸水中的临床研究[D]. 合肥: 安徽医科大学, 2018: 1-41.
30 中华医学会, 中华医学会肿瘤学分会, 中华医学会杂志社. 中华医学会肺癌临床诊疗指南(2018版)[J]. 中华肿瘤杂志, 2018, 40(12): 935-964.
Options
Outlines

/

〈 〉