Kanser Gelişiminde ve Tedavisinde Mikrobiyotanın Rolü

Öz

Her yıl milyonlarca insanın ölümüne sebep olan kanser, kardiyovasküler hastalıklardan sonra en tehlikeli hastalık grubu olarak kabul edilmektedir. Kanser tedavisi amacıyla radyoterapi, kemoterapi ve immünoterapi gibi yöntemler yaygın olarak uygulanmaktadır. Ancak, mevcut tedavi yöntemlerinin hastada olumsuz yan etkilere neden olması ek tedavi yaklaşımlarına duyulan ihtiyacı artırmaktadır. Mikrobiyotanın insan sağlığı üzerine olan etkilerine yönelik çalışmalar son yıllarda hız kazanmıştır. Kanser-mikrobiyota ilişkisi üzerine odaklanan çalışmalar ise mikrobiyotanın kanser gelişiminde ve tedavisinde önemli bir rol oynadığına işaret etmektedir. Genetik mutasyonlar, diyet, yaş, yaşam tarzı gibi risk faktörlerin yanı sıra, konak mikrobiyota çeşitliliğinin ve dengesinin bozulması da kansere sebep olan önemli etkenler arasında kabul edilmektedir. Mikrobiyota dengesinin bozulması, Helicobacter pylori, Escherichia coli, Bacteriodes fragilis ve Fusobacterium nucleatum gibi patojenlerin artmasına ve mikrobiyota çeşitliliğinin azalmasına neden olarak onkojeneze katkıda bulunmaktadır. Bunun tam aksine, dengeli bir mikrobiyota ise farkı sinyal yolaklarını uyararak anti-kanser etki gösterebilmekte ve tedavi sürecini destekleyebilmektedir. Son yıllarda, yeni mikrobiyal biyobelirteçlerin keşfi kanser teşhisinde, mikrobiyota dengesinin iyileştirilmesi ve korunması ise kanser tedavisinde oldukça önemli bir hedef haline gelmiştir. Bu derleme kapsamında mikrobiyota-kanser ilişkisi, mikrobiyal kanser biyobelirteçleri ve mikrobiyota modülasyon odaklı tedaviler dikkate alınarak özetlenmiştir.

Anahtar Kelimeler

• kanser
• mikrobiyota
• biyobelirteç
• kanser tedavisi

Role of Microbiota in Cancer Development and Treatment

Öz

Causing annual death to millions of people, cancer is considered to be the most dangerous disease followed by cardiovascular diseases. Methods such as radiotherapy, chemotherapy and immunotherapy are widely used for cancer treatment. However, the fact that current treatment methods cause negative side effects to the patients increases the need for additional treatment approaches. In recent years, research on the effects of microbiota on human health has gained momentum. Studies focused on cancer-microbiota indicate that microbiota plays an important role in cancer development and treatment. In addition to risk factors such as genetic mutations, diet, age and lifestyle, disruption of microbiota diversity and balance is also considered one of the important factors that causes cancer. Disruption of microbiota balance contributes to oncogenesis by causing an increase in pathogens such as Helicobacter pylori, Escherichia coli, Bacteriodes fragilis and Fusobacterium nucleatum and a decrease in microbiota diversity. On the contrary, a balanced microbiota can have an anti-cancer effect by stimulating different signaling pathways and support the treatment process. Recently, the discovery of new microbial biomarkers has become a very important goal in cancer diagnosis like improvement and maintenance of microbiota balance has become in cancer treatment. Within the scope of this review, the microbiota-cancer relationship is summarized, taking into account microbial cancer biomarkers and microbiota modulation focused treatments.

Anahtar Kelimeler

• cancer
• microbiota
• biomarker
• cancer treatment

Kaynakça

1. 1. Fitzmaurice C, Allen C, Barber RM, Barregard L, Bhutta ZA, Brenner H, Dicker D J, Chimed-Orchir O, Dandona R, Dandona L, Fleming T, Forouzanfar MH, Hancock J, Hay RJ, Hunter-Merrill R, Huynh C, Hosgood HD, Johnson CO, Jonas JB, et al. Global, regional, and national cancer incidence, mortality, years of life lost, years lived with disability, and disability-adjusted life-years for 32 cancer groups, 1990 to 2015: A systematic analysis for the global burden of disease study global burden. JAMA Oncology. 2017;3(4):524–548.
2. 2. Mathur G, Nain S, Sharma P. Cancer : An overview. Academic Journal of Cancer Research. 2015;8(1):1–9.
3. 3. Ferlay J, Colombet M, Soerjomataram I, et al. Cancer statistics for the year 2020: An overview. Int J Cancer. 2021;4 (5).
4. 4. Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN Estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209-249.
5. 5. Aslam MS, Naveed S, Ahmed A, Abbas Z, Gull I, et al. Side effects of chemotherapy in cancer patients and evaluation of patients opinion about starvation based differential chemotherapy. Journal of Cancer Therapy. 2014;05(08):817–822.
6. 6. Al-Taie A, Köseoǧlu A, Izzettin FV, Tezcan S, Alqozbakr T, Aksu A. Observation of dominant occurrence of radiotherapy related acute side effects and management. International Journal of Pharmacy. 2016;6(2):11–19. 7. Xu H, Cao C, Ren Y, et al. Antitumor effects of fecal microbiota transplantation: Implications for microbiome modulation in cancer treatment. Front Immunol. 2022;13:949490.
7. 8. Zwezerijnen-Jiwa FH, Sivov H, Paizs P, Zafeiropoulou K, Kinross J. A systematic review of microbiome-derived biomarkers for early colorectal cancer detection. Neoplasia. 2023;36:100868.
8. 9. Turnbaugh PJ, Ley RE, Hamady M, Fraser-Liggett CM, Knight R, Gordon JI. The human microbiome project. Nature. 2007;449(7164):804-810.

9. 10. Ding RX, Goh WR, Wu RN, et al. Revisit gut microbiota and its impact on human health and disease. J Food Drug Anal. 2019;27(3):623-631.
10. 11. Walker RW, Clemente JC, Peter I, Loos RJF. The prenatal gut microbiome: are we colonized with bacteria in utero?. Pediatr Obes. 2017;12(1):3-17.
11. 12. Dominguez-Bello MG, Costello EK, Contreras M, et al. Delivery mode shapes the acquisition and structure of the initial microbiota across multiple body habitats in newborns. Proc Natl Acad Sci U S A. 2010;107(26):11971-11975.
12. 13. Martín R, Langa S, Reviriego C, et al. Human milk is a source of lactic acid bacteria for the infant gut. J Pediatr. 2003;143(6):754-758.
13. 14. Palmer C, Bik EM, DiGiulio DB, Relman DA, Brown PO. Development of the human infant intestinal microbiota. PLoS Biol. 2007;5(7):e177.
14. 15. Koenig JE, Spor A, Scalfone N, et al. Succession of microbial consortia in the developing infant gut microbiome. Proc Natl Acad Sci U S A. 2011;108 Suppl 1(Suppl 1):4578-4585.
15. 16. Rodríguez JM, Murphy K, Stanton C, et al. The composition of the gut microbiota throughout life, with an emphasis on early life. Microb Ecol Health Dis. 2015;26:26050.
16. 17. Dekaboruah E, Suryavanshi MV, Chettri D, Verma AK. Human microbiome: an academic update on human body site specific surveillance and its possible role. Arch Microbiol. 2020;202(8):2147-2167.
17. 18. Bull MJ, Plummer NT. Part 1: The Human gut microbiome in health and disease. Integr Med (Encinitas). 2014;13(6):17-22.
18. 19. Upadhayay A, Pal D, Kumar A. Salmonella typhi induced oncogenesis in gallbladder cancer: Co-relation and progression. Advances in Cancer Biology - Metastasis. 2022;4:100032.
19. 20. Khan AA. In silico prediction of Escherichia coli proteins targeting the host cell nucleus, with special reference to their role in colon cancer etiology. J Comput Biol. 2014;21(6):466-475.
20. 21. Khan AA, A Abuderman A, Ashraf MT, Khan Z. Protein-protein interactions of HPV-Chlamydia trachomatis-human and their potential in cervical cancer. Future Microbiol. 2020;15:509-520.
21. 22. Jenkins SV, Robeson MS 2nd, Grifn RJ, Quick CM, Siegel ER, Cannon MJ, et al. Gastrointestinal tract dysbiosis enhances distal tumor progression through suppression of leukocyte trafcking. Can Res. 2019;79(23):5999–6009.
22. 23. DeGruttola AK, Low D, Mizoguchi A, Mizoguchi E. Current understanding of dysbiosis in disease in human and animal models. Inflamm Bowel Dis. 2016;22(5):1137-1150.
23. 24. Martinez JE, Kahana DD, Ghuman S, et al. Unhealthy lifestyle and gut dysbiosis: A better understanding of the effects of poor diet and cicotine on the intestinal microbiome. Front Endocrinol. 2021;12:667066.
24. 25. Wang D, DuBois RN. Immunosuppression associated with chronic inflammation in the tumor microenvironment. Carcinogenesis. 2015;36(10):1085-1093.
25. 26. Shen ZH, Zhu CX, Quan YS, et al. Relationship between intestinal microbiota and ulcerative colitis: Mechanisms and clinical application of probiotics and fecal microbiota transplantation. World J Gastroenterol. 2018;24(1):5-14.
26. 27. Hietbrink F, Besselink MG, Renooij W, et al. Systemic inflammation increases intestinal permeability during experimental human endotoxemia. Shock. 2009;32(4):374-378.
27. 28. Ernst PB, Gold BD. The disease spectrum of Helicobacter pylori: The immunopathogenesis of gastroduodenal ulcer and gastric cancer. Annu Rev Microbiol. 2000;54:615-640.
28. 29. Amieva M, Peek RM Jr. Pathobiology of Helicobacter pylori-induced gastric cancer. Gastroenterology. 2016;150(1):64-78.