NON-CANONICAL ACTIVITY OF RETINOIC ACID AS A POSSIBLE MECHANISM OF RETINOID RESISTANCE IN CANCER THERAPY
https://doi.org/10.17650/1726-9784-2019-18-4-43-50
Abstract
Retinoic acid (RA) is one of the most functionally active intracellular metabolites of vitamin A, regulating the key physiological processes, including the differentiation of cells, organs and tissues. RA is successfully applied in the treatment of acute promyelocytic leukemia. Drugs based on RA and other natural and synthetic retinoids are being actively developed for the treatment of other oncopathologies, including various solid tumors. However, the use of RA in the treatment of malignant tumors is restricted by the rapid acquisition of RA-resistance. The mechanisms of RA-resistance formation are still poorly understood, what could be explained apparently by the large number of genes directly or indirectly being regulated by RA at transcription level, including genes regulating the activity and metabolism of RA itself. The situation is further complicated by the relatively recently discovered non-genomic or non-canonical activity of RA, which consists in the non-transcriptional regulation of key protein kinases involved in tumor progression. The review is devoted to the analysis of published data on non-canonical activity of RA. The review provides a modern view on the main mechanisms implementing the canonical genomic activity of the RA, presents available information on the RA-dependent non-transcriptional regulation of ERK1 / 2, PI3K / AKT, p38MAPK and PKC protein kinases and possible mechanisms mediating this activity as well as potential significance of the RA-dependent activation of intracellular signaling pathways in the formation of RA-resistance and the malignant potential of transformed cells.
Supporting agencies: The study was performed with the support of Russian Foundation for Basic Research, project No 19-015-00027 А.
About the Authors
A. D. Enikeev
N. N. Blokhin National Medical Research Center of Oncology of the Ministry of Hearth of the Russian Federation
Russian Federation
24 Kashirskoye Shosse, Moscow 115478, Russia
Russian Federation
24 Kashirskoye Shosse, Moscow 115478, Russia
A. V. Komelkov
N. N. Blokhin National Medical Research Center of Oncology of the Ministry of Hearth of the Russian Federation
Russian Federation
24 Kashirskoye Shosse, Moscow 115478, Russia
Russian Federation
24 Kashirskoye Shosse, Moscow 115478, Russia
M. E. Akselrod
N. N. Blokhin National Medical Research Center of Oncology of the Ministry of Hearth of the Russian Federation
Russian Federation
24 Kashirskoye Shosse, Moscow 115478, Russia
Russian Federation
24 Kashirskoye Shosse, Moscow 115478, Russia
E. M. Tchevkina
N. N. Blokhin National Medical Research Center of Oncology of the Ministry of Hearth of the Russian Federation
Russian Federation
Russian Federation
24 Kashirskoye Shosse, Moscow 115478, Russia
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Review
For citations:
Enikeev A.D., Komelkov A.V., Akselrod M.E., Tchevkina E.M. NON-CANONICAL ACTIVITY OF RETINOIC ACID AS A POSSIBLE MECHANISM OF RETINOID RESISTANCE IN CANCER THERAPY. Russian Journal of Biotherapy. 2019;18(4):43-50. (In Russ.) https://doi.org/10.17650/1726-9784-2019-18-4-43-50
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