open access

Vol 71, No 2 (2021)
Review paper
Published online: 2021-04-06
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Personalised medicine in lung cancer

Izabela Łaczmańska, Izabella Dębicka, Justyna Gil, Dagmara Michałowska, Ireneusz Pawlak, Maria M. Sąsiadek
DOI: 10.5603/NJO.2021.0026
·
Nowotwory. Journal of Oncology 2021;71(2):122-128.

open access

Vol 71, No 2 (2021)
Genetics and oncology
Published online: 2021-04-06

Abstract

Personalised  therapy  is  currently  a  promising  method  of  treatment  for  cancer  patients.  The  dynamic  development  of  molecular  biology  enabled  identification  of  molecular  subtypes  of  neoplasms,  allowing  determination  of  the  optimal  therapeutic management for the patient. Molecular diagnostics is also essential for cancer diagnosis, predicting disease development and prognosis. In the case of lung cancer, which is one of the most common malignant neoplasms, the main candidates for targeted treatment are patients with stage III and IV of the disease and with no possibility of radical local treatment. In clinical practice, the most proven therapeutic agents are inhibitors of tyrosine kinase, i.e. a receptor of the epithelial growth factor (TKI-EGFR), inhibitors of ALK, ROS1, BRAF and others, as well as immunotherapy applying monoclonal antibodies against immunological system checkpoints in cases of  high level expression of programmed death receptor type 1 (PD-1) or its ligand (PD-L1), but also in cases of the high tumour mutational burden (TMB). As compared to chemotherapy, targeted therapy undoubtedly improves the treatment outcomes and, due to its lower toxicity, improves the quality of life of advanced non-small cell lung cancer patients. The aim of this paper is to characterise molecular tests  which are currently applied in qualification of non-small cell lung cancer patients for targeted therapies.

Abstract

Personalised  therapy  is  currently  a  promising  method  of  treatment  for  cancer  patients.  The  dynamic  development  of  molecular  biology  enabled  identification  of  molecular  subtypes  of  neoplasms,  allowing  determination  of  the  optimal  therapeutic management for the patient. Molecular diagnostics is also essential for cancer diagnosis, predicting disease development and prognosis. In the case of lung cancer, which is one of the most common malignant neoplasms, the main candidates for targeted treatment are patients with stage III and IV of the disease and with no possibility of radical local treatment. In clinical practice, the most proven therapeutic agents are inhibitors of tyrosine kinase, i.e. a receptor of the epithelial growth factor (TKI-EGFR), inhibitors of ALK, ROS1, BRAF and others, as well as immunotherapy applying monoclonal antibodies against immunological system checkpoints in cases of  high level expression of programmed death receptor type 1 (PD-1) or its ligand (PD-L1), but also in cases of the high tumour mutational burden (TMB). As compared to chemotherapy, targeted therapy undoubtedly improves the treatment outcomes and, due to its lower toxicity, improves the quality of life of advanced non-small cell lung cancer patients. The aim of this paper is to characterise molecular tests  which are currently applied in qualification of non-small cell lung cancer patients for targeted therapies.

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Keywords

lung cancer; NSCLC; FISH; NGS; targeted therapy; TKI

About this article
Title

Personalised medicine in lung cancer

Journal

Nowotwory. Journal of Oncology

Issue

Vol 71, No 2 (2021)

Article type

Review paper

Pages

122-128

Published online

2021-04-06

DOI

10.5603/NJO.2021.0026

Bibliographic record

Nowotwory. Journal of Oncology 2021;71(2):122-128.

Keywords

lung cancer
NSCLC
FISH
NGS
targeted therapy
TKI

Authors

Izabela Łaczmańska
Izabella Dębicka
Justyna Gil
Dagmara Michałowska
Ireneusz Pawlak
Maria M. Sąsiadek

References (42)
  1. Lindeman NI, Cagle PT, Aisner DL, et al. Updated Molecular Testing Guideline for the Selection of Lung Cancer Patients for Treatment With Targeted Tyrosine Kinase Inhibitors: Guideline From the College of American Pathologists, the International Association for the Study of Lung Cancer, and the Association for Molecular Pathology. Arch Pathol Lab Med. 2018; 142(3): 321–346.
  2. Kutkowska J, Porębska I, Rapak A. Non-small cell lung cancer - mutations, targeted and combination therapy. Postepy Hig Med Dosw (Online). 2017; 71(0): 431–445.
  3. Yuan M, Huang LL, Chen JH, et al. The emerging treatment landscape of targeted therapy in non-small-cell lung cancer. Signal Transduct Target Ther. 2019; 4: 61.
  4. 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. CA Cancer J Clin. 2018; 68(6): 394–424.
  5. Pinto JA, Vallejos CS, Raez LE, et al. Gender and outcomes in non-small cell lung cancer: an old prognostic variable comes back for targeted therapy and immunotherapy? ESMO Open. 2018; 3(3): e000344.
  6. Travis W, Brambilla E, Nicholson A, et al. The 2015 World Health Organization Classification of Lung Tumors. J Thorac Oncol. 2015; 10(9): 1243–1260.
  7. Didkowska J, Wojciechowska U, Śliwczyński A. Raport dotyczący stopni zaawansowania, leczenia oraz przeżyć pacjentów chorych na raka płuca zgłoszonych do KRN w latach 2014-2016. 2020.
  8. Gatzemeier U, Pluzanska A, Szczesna A, et al. Phase III study of erlotinib in combination with cisplatin and gemcitabine in advanced non-small-cell lung cancer: the Tarceva Lung Cancer Investigation Trial. J Clin Oncol. 2007; 25(12): 1545–1552.
  9. Allemani C, Weir HK, Carreira H, et al. CONCORD Working Group. Global surveillance of cancer survival 1995-2009: analysis of individual data for 25,676,887 patients from 279 population-based registries in 67 countries (CONCORD-2). Lancet. 2015; 385(9972): 977–1010.
  10. Antonia SJ, Villegas A, Daniel D, et al. PACIFIC Investigators. Durvalumab after Chemoradiotherapy in Stage III Non-Small-Cell Lung Cancer. N Engl J Med. 2017; 377(20): 1919–1929.
  11. Forsythe ML, Alwithenani A, Bethune D, et al. Molecular profiling of non-small cell lung cancer. PLoS One. 2020; 15(8): e0236580.
  12. Tsoukalas N, Aravantinou-Fatorou E, Baxevanos P, et al. Advanced small cell lung cancer (SCLC): new challenges and new expectations. Ann Transl Med. 2018; 6(8): 145.
  13. Mosele F, Remon J, Mateo J, et al. Recommendations for the use of next-generation sequencing (NGS) for patients with metastatic cancers: a report from the ESMO Precision Medicine Working Group. Ann Oncol. 2020; 31(11): 1491–1505.
  14. Harlé A, Dietmaier W, Vogl I, et al. Detection of ALK, RET, ROS1, NTRK1 and MET rearrangements and actionable mutations using next generation sequencing in patients with non-small cell lung cancer. Ann Oncol. 2018; 29: vi12.
  15. Clavé S, Rodon N, Pijuan L, et al. Next-generation Sequencing for ALK and ROS1 Rearrangement Detection in Patients With Non-small-cell Lung Cancer: Implications of FISH-positive Patterns. Clin Lung Cancer. 2019; 20(4): e421–e429.
  16. Rizvi H, Sanchez-Vega F, La K, et al. Molecular Determinants of Response to Anti-Programmed Cell Death (PD)-1 and Anti-Programmed Death-Ligand 1 (PD-L1) Blockade in Patients With Non-Small-Cell Lung Cancer Profiled With Targeted Next-Generation Sequencing. J Clin Oncol. 2018; 36(7): 633–641.
  17. Qian J, Massion P. Next-generation molecular therapy in lung cancer. Translational Lung Cancer Research. 2018; 7(S1): S31–S34.
  18. Non-Small Cell Lung Carcinoma - My Cancer Genome [Internet]. https://www.mycancergenome.org/content/disease/non-small-cell-lung-carcinoma/ (30.12.2020).
  19. Ruiz-Cordero R, Devine W. Targeted Therapy and Checkpoint Immunotherapy in Lung Cancer. Surgical Pathology Clinics. 2020; 13(1): 17–33.
  20. Krawczyk P, Chorostowska-Wynimko J, Dziadziuszko R, et al. Zalecenia metodyczne dotyczące oceny mutacji genu EGFR oraz rearanżacji genu ALK w kwalifikacji chorych na niedrobnokomórkowego raka płuca do terapii ukierunkowanych molekularnie. Nowotwory. Journal of Oncology. 2014; 64(4): 336–342.
  21. Strom SP, Strom SP. Current practices and guidelines for clinical next-generation sequencing oncology testing. Cancer Biology & Medicine. 2016; 13(1): 3–11.
  22. Hochmair MJ, Buder A, Schwab S, et al. Liquid-Biopsy-Based Identification of EGFR T790M Mutation-Mediated Resistance to Afatinib Treatment in Patients with Advanced EGFR Mutation-Positive NSCLC, and Subsequent Response to Osimertinib. Target Oncol. 2019; 14(1): 75–83.
  23. Evrard SM, Taranchon-Clermont E, Rouquette I, et al. Multicenter Evaluation of the Fully Automated PCR-Based Idylla EGFR Mutation Assay on Formalin-Fixed, Paraffin-Embedded Tissue of Human Lung Cancer. J Mol Diagn. 2019; 21(6): 1010–1024.
  24. Du X, Shao Y, Qin HF, et al. ALK-rearrangement in non-small-cell lung cancer (NSCLC). Thorac Cancer. 2018; 9(4): 423–430.
  25. Thunnissen E, Bubendorf L, Dietel M, et al. EML4-ALK testing in non-small cell carcinomas of the lung: a review with recommendations. Virchows Arch. 2012; 461(3): 245–257.
  26. Sholl LM, Weremowicz S, Gray SW, et al. Combined use of ALK immunohistochemistry and FISH for optimal detection of ALK-rearranged lung adenocarcinomas. J Thorac Oncol. 2013; 8(3): 322–328.
  27. Wang R, Pan Y, Li C, et al. The use of quantitative real-time reverse transcriptase PCR for 5' and 3' portions of ALK transcripts to detect ALK rearrangements in lung cancers. Clin Cancer Res. 2012; 18(17): 4725–4732.
  28. Zhang X, Zhou JG, Wu HL, et al. Diagnostic accuracy of PCR for detecting ALK gene rearrangement in NSCLC patients: A systematic review and meta-analysis. Oncotarget. 2017; 8(43): 75400–75410.
  29. Santini FC, Hellmann MD. PD-1/PD-L1 Axis in Lung Cancer. Cancer J. 2018; 24(1): 15–19.
  30. Brahmer J, Reckamp KL, Baas P, et al. Nivolumab versus Docetaxel in Advanced Squamous-Cell Non-Small-Cell Lung Cancer. N Engl J Med. 2015; 373(2): 123–135.
  31. Potempa M, Jonczyk P, Zalewska-Ziob M. Molekularne uwarunkowania raka płuca. Onkol w Prakt Klin Medica. 2014; 10(4): 199–211.
  32. Schulze AB, Schmidt LH. PD-1 targeted Immunotheray as first-line theray for advanced non-small-cell lung cancer atients. Journal of Thoracic Disease. 2017; 9: E384–E386.
  33. LECZENIE NIEDROBNOKOMÓRKOWEGO RAKA PŁUCA (od 09-2020). Ministerstwo Zdrowia.
  34. Greillier L, Tomasini P, Barlesi F. The clinical utility of tumor mutational burden in non-small cell lung cancer. Transl Lung Cancer Res. 2018; 7(6): 639–646.
  35. Goodman AM, Kato S, Bazhenova L, et al. Tumor Mutational Burden as an Independent Predictor of Response to Immunotherapy in Diverse Cancers. Mol Cancer Ther. 2017; 16(11): 2598–2608.
  36. McGranahan N, Furness AJS, Rosenthal R, et al. Clonal neoantigens elicit T cell immunoreactivity and sensitivity to immune checkpoint blockade. Science. 2016; 351(6280): 1463–1469.
  37. Paz-Ares L, Ciuleanu TE, Cobo M, et al. CheckMate 026 Investigators. First-Line Nivolumab in Stage IV or Recurrent Non-Small-Cell Lung Cancer. N Engl J Med. 2017; 376(25): 2415–2426.
  38. Gu Li, Deng ZJ, Roy S, et al. A Combination RNAi-Chemotherapy Layer-by-Layer Nanoparticle for Systemic Targeting of KRAS/P53 with Cisplatin to Treat Non-Small Cell Lung Cancer. Clin Cancer Res. 2017; 23(23): 7312–7323.
  39. Xie Q, Yu Z, Lu Y, et al. microRNA-148a-3p inhibited the proliferation and epithelial-mesenchymal transition progression of non-small-cell lung cancer via modulating Ras/MAPK/Erk signaling. J Cell Physiol. 2019; 234(8): 12786–12799.
  40. Engelman JA, Zejnullahu K, Mitsudomi T, et al. MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling. Science. 2007; 316(5827): 1039–1043.
  41. Lazzari C, Sitaleri G, Catania C, et al. Targeting ALK in atients with advanced Non Small Cell Lung Cancer: Biology, diagnostic and theraeutic otions. Critical Reviews in Oncology/Hematology. Crit Rev Oncol Hematol. 2014; 89: 358–365.
  42. Lockney NA, Wu AJ. Alectinib for the management of ALK-positive non-small cell lung cancer brain metastases. J Thorac Dis. 2017; 9(2): E152–E154.

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