Cancer Stem Cell-Targeted Therapy: Harapan Baru Terapi Kanker

I GUSTI AYU ARTINI* -  Bagian Farmakologi Fakultas Kedokteran Universitas Udayana Bali, Indonesia

DOI : 10.14414/ijoc.v9i3.389

Cancer stem cell (CSC) is subpopulation of tumor cell that posses stem cell properties such as self-renewal capacity and able to produce heterogenous progeny. CSC has been said to be related to cancer development, recurrency, metastasis, and resistance to conventional therapy. Signaling pathway responsible for proliferation and differentiation of CSC are Notch, Hedgehog and Wnt pathway. CSC eradication can be achieved by administering drug or gene-specific molecule targeted to CSC-specific pathway, CSC marker, DNA repair mechanism, apoptosis inhibitor, CSC microenvironment (niche), differentiation therapy, or delivering drug as polymer conjugate (nanocarrier)

Cancer stem cell (CSC) adalah subpopulasi sel tumor yang memiliki properti stem cell, yaitu memiliki kemampuan memperbarui diri dan dapat menghasilkan turunan yang heterogen. Keberadaan CSC dikatakan berkaitan dengan perkembangan kanker, rekurensi, metastasis, dan resistansi terhadap terapi konvensional. Jalur sinyaling yang berperan dalam proliferasi dan diferensiasi CSC adalah jalur Notch, Hedgehog, dan Wnt. Eradikasi CSC dapat dicapai dengan obat atau molekul spesifik yang menarget jalur sinyaling CSC, penanda CSC, mekanisme perbaikan DNA, inhibitor apoptosis, lingkungan mikro CSC (niche), terapi diferensiasi, atau mengirim obat dalam bentuk konjugat polimer (nanocarrier).

Keywords
cancer stem cell, targeting, nanoparticle
  1. Ciurea ME, Georgescu AM, Purcaru SO, Artene SA, Emami GH, Boldeanu MV, Tache DE, Dricu A. Cancer stem cells, biological functions and therapeutically targeting. International Journal of Molecullar Sciences 2014;15:8169-8185.
  2. Ablett MP, Singh JK, Clarke RB. Stem cells in breast tumours: are they ready for the clinic? European Journal of Cancer 2012;48:2104-2116.
  3. Hu Y dan Fu L. Targeting cancer stem cells: a new therapy to cure cancer patients. American Journal of Cancer Research 2012;2(3):340-356.
  4. Tu LC, Foltz G, Lin E, Hood L, Tian Q. Targeting stem cells: clinical implication for cancer therapy. Current Stem Cell Research Therapy 2009;4(2):147-153.
  5. La Porta CAM. Thoughts about cancer stem cells in solid tumors. World Journal of Stem Cells 2012;4(3):17-20.
  6. Vinogradov S dan Wei X. Cancer stem cells and drug resistance: the potential of nanomedicine. Nanomedicine 2012 Gottschling S, Schnabel PA, Herth FJF, Herpel E. Are we missing the target? Cancer stem cells and drug resistance in non small cell lung cancer. Cancer Genomics and Proteomics 2012;9:275-286.
  7. Mimeault M dan Batra SK. Targeting of cancer stem/progenitor cells plus stem cell-based therapies: the ultimate hope for treating and curing aggressive and recurrent cancers. Panminerva Medicine 2008;50(1):3-18.
  8. Niero ELO, Rocha-Sales B, Lauand C, Cortez BA, de Souza MM, Rezende-Teixeira P, Urabayashi MS, Martens AA, Neves JH, Machado-Santelli GM. The multiple facets of drug resistance: one history, different approaches. Journal of Experimental and Clinical Cancer Research 2014;33:37.
  9. Tomao F, Papa A, Strudel M, Rossi L, Lo Russo G, Panici PB, Ciabatta FR, Tomao S. Investigating molecular profiles of ovarian cancer: an update on cancer stem cells. Journal of Cancer 2014;5:301-310.
  10. Skidan I dan Steiniger SCJ. In vivo models for cancer stem cell research: a practical guide for frequently used animal models and available biomarkers. Journal of Physiology and Pharmacology 2014;65(2):157-169.
  11. Wakamatsu Y, Sakamoto N, Oo HZ, Naito Y, Uraoka N, Anami K, Sentani K, Oue N, Yasui W. Expression of cancer stem cell markers ALDH1, CD44 and CD133 in primary tumor and lymph node metastasis of gastric cancer. Pathology International 2012;62:112-119.
  12. Mimeault M, Hauke R, Mehta PP, Batra SK. Recent advances in cancer stem/progenitor cell research: therapeutic implications for overcoming resistance to the most aggressive cancers. Journal of Cellular and Molecular Medicine 2007;11(5):981-1011.
  13. Shtivelman E, Hensing T, Simon GR, Dennis PA, Otterson GA, Bueno R, Salgia R. Molecular pathways and therapeutic targets in lung cancer. Impact Journal 2014:1-34.
  14. Yeh CT, Wu ATH, Chang PMH, Chen KY, Yang CN, Yang SC, Ho CC, Chen CC, Kuo YL, Lee PY, Liu YW, Yen CC, Hsiao M, Lu PJ, Lai JM, Wang LS, Wu CH, Chiou JF, Yang PC, Huang CYF. Trifluoperazine, an antipsychotic agent, inhibits cancer stem cell growth and overcomes drug resistance of lung cancer. American Journal of Respiratory and Critical Care Medicine 2012;186(11):1180-1188.
  15. Han L, Shi S, Gong T, Zhang Z, SunX. Cancer stem cell: therapeutic implications and perspectives in cancer therapy. Acta Pharmaceutic Sinica B. 2013; 3(2): 65-75. Chen K, Huang YH, Chen JI. Understanding and targeting cancer stem cells: therapeutic implications and challenges. Acta Pharmacologica Sinica. 2013; 34: 732-740.
  16. Liao K, Xia B, Zhuang QY, Hou MJ, Zhang YJ, Luo B, Qiu Y, Gao YF, Li XJ, Chen HF, Ling WH, He CY, Huang YJ, Lin YC, Lin ZN. Parthenolide inhibits cancer stem-like side population of nasopharyngeal carcinoma cells via suppression of the NF?B/COX-2 pathway. Theranostics. 2015; 5(3): 302-322.
  17. Chung SS dan Vadgama JV. Curcumin and epigallocatechin gallate inhibit the cancer stem cell phenotype via down regulation of STAT3-NF?B signaling. Anticancer Research. 2015; 35(1): 39-46.
  18. Hirsch HA, Iliopoulos D, Struhl K. Metformin inhibits the inflammatory response associated with cellular transformation and cancer stem cell growth. PNAS 2013;110(3):972-979.
  19. Kim BYS, Rutka JT, Chan WCW. Nanomedicine. New England Journal of Medicine 2010;363:2434-43.
  20. Koziel JE dan Herbert BS. The telomerase inhibitor imetelstat alone, and in combination with trastuzumab, decreases the cancer stem cell population and self-renewal of HER2(+) breast cancer cells. Breast Cancer Research and Treatment
  21. ; 149(3): 607-618.
  22. Sun R, Liu Y, Li SY, Shen S, Du XJ, Xu CF, Cao ZT, Bao Y, Zhu YH, Li YP, Yang XZ, Wang J. Codelivery of all-transretinoic acid and doxorubicin for cancer therapy with synergistic
  23. inhibition of cancer stem cells. Biomaterials 2015; 37: 405-414.
  24. Prokopi M, Kousparou CA, Epenetos AA. The secret role of microRNAs in cancer stem cell development and potential therapy : a notch pathway approach. Cancer Molecular Target and Therapeutics 2015; 4(389): 1-6.
  25. Jain S dan Das M. Conference scene: nanomedicine kindles the development of the elixir of life. Nanomedicine 2011;6(4):599-603.
  26. Nie S. Understanding and overcoming major barriers in cancer nanomedicine. Nanomedicine 2010;5(4):523528.
  27. Podila R dan Brown JM. Toxicity of engineered nanomaterials: a physicochemical perspective. Journal of Biochemical Molecular Toxicology 2013;27(1):50-55.
  28. Tomao F, Papa A, Rossi L, Strudel M, Vici P, Lo Russo G, Tomao S. Emerging role of cancer stem cells in the biology and treatment of ovarian cancer: basic knowledge and therapeutic possibilities for an innovative approach. Journal
  29. of Experimental and Clinical Cancer Research 2013;32:48

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Article Info
Submitted: 2015-11-19
Published: 2015-11-23
Section: Research Articles
Article Statistics: 686 325