Article 11220

Title of the article



Brosalov Vladimir Mikhaylovich, Assistant, sub-department of human physiology, Medical Institute, Penza State University (40 Krasnaya street, Penza, Russia), E-mail:
Sudapina Alina Rashidovna, Student, Medical Institute, Penza State University (40 Krasnaya street, Penza, Russia), E-mail:
Mikulyak Nadezhda Ivanovna, Doctor of medical sciences, associate professor, head of the sub-department of human physiology, Medical Institute, Penza State University (40 Krasnaya street, Penza, Russia), E-mail: 

Index UDK





Breast cancer is extremely heterogeneous in its clinical, morphological and molecular genetic characteristics. Despite early detection and increased knowledge of its biology and chemoresistance, metastatic breast cancer is a largely incurable disease. The constantly increasing trend in the development of this malignant neoplasm leads to the need to search for new methods of diagnosis, treatment and prognosis. One of the main reasons complicating treatment is the heterogeneity of the tumor. It is observed in individual patients (inter-tumor) and in each individual tumor (intratumor). The review presents modern studies demonstrating the concept of clonal selection as a key link of intra-tumor heterogeneity. In the process of evolution, the subclones of tumor cells are arbitrarily subjected to various mutations or epigenetic changes that lead to the transformation of molecular and biological characteristics, which is a leading factor for the adaptation of tumor cells (including the damaging effect of chemotherapy drugs) and further tumor progression. Thus, metastasis and the formation of resistance to therapy (the main causes of adverse outcomes in patients with malignant tumors) may be due to the process of clonal evolution. The study of this concept, its mechanisms and influence on the clinical course is one of the promising methods in Oncology. 

Key words

clonal evolution, intra-tumor heterogeneity, breast cancer 

Download PDF

1. Kaprin A. D., Starinskiy V. V., Petrova G. V. Zlokachestvennye novoobrazovaniya v Rossii v 2018 godu (zabolevaemost' i smertnost') [Malignant neoplasms in Russia in 2018 (morbidity and mortality)]. Moscow: MNIOI im. P. A. Gertsena – filial FGBU «NMITs radiologii» Minzdrava Rossii, 2019, pp. 4–91. [In Russian]
2. Tabassum D. P., Polyak K. Nature Reviews Cancer. 2015, vol. 15, no. 8, pp. 473–483.
3. McGranahan N., Swanton C. Cell. 2017, vol. 168, no. 4, pp. 613–628.
4. Hortobagyi G. N., D’orsi C. J., Edge S. B., Mittendorf E. A., Rugo H. S., Solin L. J. AJCC Cancer Staging Manual – Breast. 8th ed. Chicago: Springer, 2017.
5. Harris L. N., Ismaila N., McShane L. M., Andre F., Collyar D. E., Gonzalez-Angulo A. M., Hayes D. F. Journal of Clinical Oncology. 2016, vol. 34 (10), pp. 1134–1150.
6. Turashvili G., Brogi E. Frontiers in Medicine. 2017, no. 4, pp. 11–15.
7. Januškevičienė I., Petrikaitė V. Life Sciences. 2019, vol. 239, pp. 1–10.
8. Koren S., Bentires-Alj M. Mol Cell. 2015, vol. 60 (4), pp. 537–546.
9. Fang Yang, Yucai Wang, Quan Li, Lulu Cao, Zijia Sun, Juan Jin, Hehui Fang, Aiyu Zhu, Yan Li, Wenwen Zhang, Yanru Wang, Hui Xie, Jan-Åke Gustafsson, Shui Wang, Xiaoxiang Guan Carcinogenesis. 2017, vol. 38, pp. 200–209.
10. Stanta G., Bonin S. Frontiers in Medicine. 2018, vol. 5, pp. 1–10.
11. Wang Y., Waters J., Leung M. et al. Nature. 2014, vol. 512, pp. 155–160.
12. La Porta C. A. M., Zapperi S. Semin Cancer Biol. 2017, vol. 44, pp. 3–9.
13. Robinson N. J., Taylor D. J., Schiemann W. P. Journal of Cancer Metastasis and Treatment. 2019, vol. 5, p. 39.
14. Kreso A., Dick J. E. Cell Stem Cell. 2014, no. 14, pp. 275–291.
15. Ibragimova M. K., Tsyganov M. M., Litvyakov N. V. Biokhimiya [Biochemistry]. 2017, vol. 82, no. 4, pp. 572–586. [In Russian]
16. Gerashchenko T. S., Zav'yalova M. V., Denisov E. V., Krakhmal' N. V., Pautova D. N., Litvyakov N. V., Vtorushin S. V., Cherdyntseva N. V., Perel'muter V. M. Acta Naturae. 2017, no. 1, pp. 60–72.
17. Roulot A., Héquet D., Guinebretière J.-M., Vincent-Salomon A., Lerebours F., Dubot C., Rouzier R. Annales de Biologie Clinique [Annals of Clinical Biology]. 2016, no. 74 (6), pp. 653–660.
18. Smid M., Rodríguez-González F., Sieuwerts A. et al. Nat Commun. 2016, vol. 7.
19. Sedakov I. E., Smirnov V. N., Motriy A. V., Skochilyas T. L., Sadritskaya Ya. V., Motriy M. O. Novoobrazovanie [Neoplasm]. 2019, vol. 11, no. 2, pp. 58–62. [In Russian]
20. Zardavas D., Irrthum A., Swanton C., Piccart M. Nat Rev Clin Oncol. 2015, no. 12, pp. 381–394.
21. Koboldt D., Fulton R., McLellan M. et al. Nature. 2012, vol. 490 (7418), pp. 61–70.
22. Zhang J., Baran J., Cros A., Guberman J. M., Haider S., Hsu J. et al. Database. 2011, Bar026. DOI 10.1093/database/bar026
23. Gillies R. J., Verduzco D., Gatenby R. A. Nature Reviews Cancer. 2012, vol. 12, no. 7, p. 487.
24. Yates L., Gerstung M., Knappskog S. et al. Nat Med. 2015, no. 7, pp. 751–759.
25. Beca F., Polyak K. Adv Exp Med Biol. 2016, vol. 882, pp. 169–189. DOI 10.1007/978-3-319-22909-6_7.
26. Eirew P., Steif A., Khattra J. et al. Nature. 2015, vol. 518, pp. 422–426. DOI 10.1038/nature13952.
27. Wang Y., Waters J., Leung M. et al. Nature. 2014, vol. 512, pp.155–160.
28. Kalinowski L., Saunus J. M., A. E. McCart Reed, & Lakhani S. R. Adv Exp Med Biol., 2019, vol. 1152, pp. 75–104. DOI 10.1007/978-3-030-20301-6_6.
29. Sharma P., Hu-Lieskovan S., Wargo J. A., Ribas A. Cell. 2017, vol. 168, no. 4, pp. 707–723.
30. Martinelli E., Morgillo F., Troiani T., Ciardiello F. Cancer treatment reviews. 2017, vol. 53, pp. 61–69.
31. Sabaawy H. E. Journal of leukemia. 2013, vol. 1, no. 4, pp. 100–124.
32. Barber L. J., Davies M. N., Gerlinger M. Current opinion in genetics & development. 2015, vol. 30, pp. 1–6.
33. Litvyakov N. V. et al. Genetika cheloveka i patologiya: XI nauchnaya konferentsiya, (Tomsk, 27–30 noyabrya) [Human genetics and pathology: XI scientific conference (Tomsk, November 27-30)]. Tomsk, 2017, pp. 124–125. [In Russian]
34. Gerlinger M., McGranahan N., Dewhurst S. M., Burrell R. A., Tomlinson I. et al. Annu Rev Genet. 2014, vol. 81 (3), pp. 215–236.


Дата создания: 23.06.2020 08:47
Дата обновления: 31.08.2020 13:35