Molecular mechanisms of resistance development under targeted therapy on the example of cutaneous melanoma


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Abstract

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.

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About the authors

T. G Ruksha

Professor V. F. Voino-Yasenetsky Krasnoyarsk State Medical University

Email: tatyana_ruksha@mail.ru
Head of the Department of pathological physiology. Krasnoyarsk State Medical University. MD, professor Partizana Zheleznyaka str., 1, Krasnoyarsk, 660022, Russian Federation

D. S Zemtsov

Professor V. F. Voino-Yasenetsky Krasnoyarsk State Medical University

Email: danil_zemtsov@mail.ru
PhD student of the Pathological Physiology Department. Krasnoyarsk State Medical University Partizana Zheleznyaka str., 1, Krasnoyarsk, 660022, Russian Federation

S. N Lavrentiev

Professor V. F. Voino-Yasenetsky Krasnoyarsk State Medical University

Email: semyonlavrentev@mail.ru
PhD student of the Pathological Physiology Department. Krasnoyarsk State Medical University. Partizana Zheleznyaka str., 1, Krasnoyarsk, 660022, Russian Federation

N. V Palkina

Professor V. F. Voino-Yasenetsky Krasnoyarsk State Medical University

Email: mosmannv@yandex.ru
assistant of the Department of pathological physiology. Krasnoyarsk State Medical University. Candidate of medical Sciences Partizana Zheleznyaka str., 1, Krasnoyarsk, 660022, Russian Federation

A. R Yessimbekova

Professor V. F. Voino-Yasenetsky Krasnoyarsk State Medical University

Email: aleksandra.esimbekova.96@mail.ru
PhD student of the Pathological Physiology Department. Krasnoyarsk State Medical University Partizana Zheleznyaka str., 1, Krasnoyarsk, 660022, Russian Federation

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