Application of Molecular Diagnostics Technology in the Development of a Companion Diagnostics for Malignant Solid Tumors

악성 고형암의 항암제 동반진단 기술에서 분자진단기술의 적용

Kim, Jin-Hee

  • Received : 2019.01.23
  • Accepted : 2019.02.27
  • Published : 2019.03.28


Unlike benign tumors, malignant tumors are capable of metastasis, easy to relapse, poor survival, and low quality of life. In Korea, here is a tendency to treat the tumors collectively according to the General Principles of Cancer Chemotherapy(GPCC) of the Health Insurance Review & Assessment Service (HIRA). But recently, companion diagnostics(CDx) is recommended rather than unilateral medication because biomarker-based molecular diagnostics is possible to predict the drug response of patients before drug treatment. Not only domestic but also overseas Food and Drug Administratio (FDA) recommends the development of the CDx system at the stage of drug development to ensure the responsiveness and safety of medicines. In this study, I focused on the necessity of CDx development direction as well as CDx development status through literature review. Furthermore I also discussed CDx types according to the molecular diagnostic technology such as immunohistochemistry (IHC), polymerase chain reaction (PCR), in situ hybridization (ISH), and next-generation sequencing (NGS) not only in the approved CDx but also in the developing one by US FDA. And I suggested the technology issue of CDx development process such as a selection of molecular diagnostics at the time of release, a clear understanding of the CDx mechanism, and a convergence of drug with CDx development. The necessity of social insurance system also was proposed for CDx development.


Malignant Tumor;Solid Tumor;Companion Diagnostics;Molecular Diagnostics Technology


  1. P. Bumming, J. Andersson, J. M. Meis-Kindblom, H. Klingenstierna, K. Engstrom, U. Stierner, B. Wangberg, S. Jansson, H. Ahlman, L. G. Kindblom, and B. Nilsson, "Neoadjuvant, adjuvant and palliative treatment of gastrointestinal stromal tumours (GIST) with imatinib: a centre-based study of 17 patients," British journal of cancer, Vol.89, No.3, pp.460-464, 2003.
  2. A. G. Hall and M. J. Tilby "Mechanisms of action of, and modes of resistance to, alkylating agents used in the treatment of haematological malignancies," Blood review, Vol.6, No.3, pp.163-173, 1992.
  3. J. Bardy, N. J. Slevin, K. L. Mais, and A. Molassiotis, "A systematic review of honey uses and its potential value within oncology care," Journal of Clinical Nursing, Vol.17, No.9, pp.2661-2664, 2008.
  4. T. A. Baudino, "Targeted Cancer Therapy: The Next Generation of Cancer Treatment. Current drug discovery technologies," Current drug discovery technologies, Vol.12, No.1, pp.3-20, 2001.
  5. M. Jamal-Hanjani, A. Hackshaw, Y. Ngai, J. Shaw, C. Dive, and S. Quezada, "Tracking genomic cancer evolution for precision medicine: the lung TRACERx study," PLoS Biol, Vol.12, p.e1001906, 2014.
  6. M. Goozner, "Drug approvals 2011: focus on companion diagnostics," Journal of the National Cancer Institute, Vol.104, No.2, pp.84-86, 2012.
  7. National Evidence-based healthcare Collaborating Agency, Development of Guidelines for New Health Technology Assessment, 2014.
  8. National Institute of Food and Drug Safety Evaluation, Review guidelines for Market Authorization (IVD Companion Diagnostics). Cheongju: National Institute of Food and Drug Safety Evaluation, 2015.
  9. C. S. Karapetis, S. Khambata-Ford, D. J. Jonker, C. J. O'Callaghan, D. Tu, N. C. Tebbutt, R. J. Simes, H. Chalchal, J. D. Shapiro, S. Robitaille, T. J. Price, L. Shepherd, H. J. Au, C. Langer, M. J. Moore, and J. R. Zalcberg, "K-ras mutations and benefit from cetuximab in advanced colorectal cancer," N Engl J Med, Vol.359, No.17, pp.1757-1765, 2008.
  10. B. J. Solomon, T. Mok, D. W. Kim, Y. L. Wu, K. Nakagawa, T. Mekhail, E. Felip, F. Cappuzzo, J. Paolini, T. Usari, S. Iyer, A. Reisman, K. D. Wilner, J. Tursi, and F. Blackhall, "First-line crizotinib versus chemotherapy in ALK-positive lung cancer," N Engl J Med, Vol.371, No.23, pp.2167-2177, 2014.
  11. T. W. Jacobs, A. M. Gown, H. Yaziji, M. J. Barnes, and S. J. Schnitt, "Specificity of HercepTest in determining HER-2/neu status of breast cancers using the United States Food and Drug Administration-approved scoring system," J Clin Oncol, Vol.7, No.7, pp.1983-1987, 1999.
  12. A. Agarwal, D. Ressler, and G. Snyder, "The current and future state of companion diagnostics," Pharmgenomics Pers Med, Vol.31, No.87, pp.99-110, 2015.
  13. 신영기, "표적항암제 동반진단키트의 현재와 전망," 생명공학정책연구, Vol.4, 2014.
  14. P. Rubin and G. Casarett, "Microcirculation of tumors. I. Anatomy, function, and necrosis," Clin Radiol, Vol.17, pp.220-229, 1966.
  15. R. K. Jain, "Determinants of tumor blood flow: a review," Cancer Res, Vol.48, pp.2641-2658, 1988.
  16. W. H. Clark, "Tumour progression and the nature of cancer," Br. J. Cancer, Vol.64, No.4, pp.631-644, 1991.
  17. B. A. Chabner and T. G. Roberts, "Timeline: Chemotherapy and the war on cancer," Nature reviews cancer, Vol.5, No.1, pp.65-72, 2005.
  18. M. S. Tsao, A. Sakurada, J. C. Cutz, C. Q. Zhu, S. Kamel-Reid, J. Squire, I. Lorimer, T. Zhang, N. Liu, M. Daneshmand, P. Marrano, G. da Cunha Santos, A. Lagarde, F. Richardson, L. Seymour, M. Whitehead, K. Ding, J. Pater, and F. A. Shepherd, "Erlotinib in lung cancer-molecular and clinical predictors of outcome," N Engl J Med, Vol.353, No.2, pp.133-144, 2005.
  19. M. Reck, D. Rodriguez-Abreu, A. G. Robinson, R. Hui, T. Csoszi, A. Fulop, M. Gottfried, N. Peled, A. Tafreshi, S. Cuffe, M. O'Brien, S. Rao, K. Hotta, M. A. Leiby, G. M. Lubiniecki, Y. Shentu, R. Rangwala, and J. R. Brahmer, "Pembrolizumab versus Chemotherapy for PD-L1-Positive Non-Small-Cell Lung Cancer," N Engl J Med, Vol.375, No.19, pp.1823-1833, 2016.
  20. Ryan Bishop, "Applications of fluorescence in situ hybridization (FISH) in detecting genetic aberrations of medical significance," Bioscience Horizons, Vol.3, No.1, pp.85-95, 2010.
  21. A. Agarwal, D. Ressler, and G. Snyder, "The current and future state of companion diagnostics," Pharmgenomics Pers Med, Vol.8, pp.99-110, 2015.
  22. S. A. Hardwick, I. W. Deveson, and T. R. Mercer, "Reference standards for next-generation sequencing," Nat Rev Genet, Vol.18, No.8, pp.1473-484, 2017.
  23. S. A. Waldman and A. Terzic, "Companion diagnostics at the intersection of personalized medicine and healthcare delivery," Biomark Med, Vol.9, No.1, pp.1-3, 2015.
  24. E. Faulkner, L. Annemans, L. Garrison, M. Helfand, A. P. Holtorf, J. Hornberger, D. Hughes, T. Li, D. Malone, K. Payne, U. Siebert, A. Towse, D. Veenstra, and J. Watkins, "Challenges in the development and reimbursement of personalized medicine-payer and manufacturer perspectives and implications for health economics and outcomes research: a report of The ISPOR Personalized Medicine Special Interest Group," Value Health, Vol.15, pp.1162-1171, 2012.


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