MOLECULAR MECHANISMS OF RESISTANCE DEVELOPMENT UNDER TARGETED THERAPY ON THE EXAMPLE OF CUTANEOUS MELANOMA

DOI: https://doi.org/10.29296/24999490-2020-06-02

T.G. Ruksha, D.S. Zemtsov, S.N. Lavrentiev, N.V. Palkina, A.R. Yessimbekova Professor V. F. Voino-Yasenetsky Krasnoyarsk State Medical University, Partizana Zheleznyaka str., 1, Krasnoyarsk, 660022, Russian Federation E-mail: [email protected] Semyon Lavrentiev – PhD student of the Pathological Physiology Department. Krasnoyarsk State Medical University. Tel.: +7 (3912) 28-36-49. E-mail: [email protected]. ORCID: 0000-0002-2214-1336 Nadezhda Palkina – assistant of the Department of pathological physiology. Krasnoyarsk State Medical University. Candidate of medical Sciences. Tel.: +7 (3912) 28-36-49. E-mail: [email protected]. ORCID: 0000-0002-6801-3452 Alexandra Yesimbekova – PhD student of the Pathological Physiology Department. Krasnoyarsk State Medical University. Тел.: +7 (3912) 28-36-49. E-mail: [email protected]. ORCID: 0000-0001-6363-5941

Cutaneous melanoma is a highly heterogeneous malignancy, which characterized by low effectiveness of chemotherapeutic antitumor agents. 50% of melanomas have a somatic mutation in BRAF oncogene, leading to uncontrolled activation of mitogen-activated protein kinase signaling cascade ensuring the proliferation and survival of tumor cells. The blocking of the BRAF gene mutation effects seemed to be a reasonable way to increase the effectiveness of melanoma therapy. However, the effectiveness of melanoma treatment in many patients is limited up to six months due to the development of acquired resistance. Acquired chemoresistance is related to the reactivation of signal pathways involved in the control of cell proliferation. Besides, several BRAF-positive melanomas exhibit intrinsic resistance due to mutations in tumor suppressor genes. Unveiling molecular mechanisms of chemoresistance to targeted therapy will allow developing more effective strategies for cancer diseases. This paper provides a review of the literature and our data as well as the results of clinical studies on a variety of resistance mechanisms and strategies for their elimination.
Keywords: 
vemurafenib, melanoma, BRAFV600E, resistance
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