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Targeting mTOR signaling pathways in multiple myeloma: biology and implication for therapy

Authors :
Yanmeng Wang
Niels Vandewalle
Kim De Veirman
Karin Vanderkerken
Eline Menu
Elke De Bruyne
Source :
Cell Communication and Signaling, Vol 22, Iss 1, Pp 1-17 (2024)
Publication Year :
2024
Publisher :
BMC, 2024.

Abstract

Abstract Multiple Myeloma (MM), a cancer of terminally differentiated plasma cells, is the second most prevalent hematological malignancy and is incurable due to the inevitable development of drug resistance. Intense protein synthesis is a distinctive trait of MM cells, supporting the massive production of clonal immunoglobulins or free light chains. The mammalian target of rapamycin (mTOR) kinase is appreciated as a master regulator of vital cellular processes, including regulation of metabolism and protein synthesis, and can be found in two multiprotein complexes, mTORC1 and mTORC2. Dysregulation of these complexes is implicated in several types of cancer, including MM. Since mTOR has been shown to be aberrantly activated in a large portion of MM patients and to play a role in stimulating MM cell survival and resistance to several existing therapies, understanding the regulation and functions of the mTOR complexes is vital for the development of more effective therapeutic strategies. This review provides a general overview of the mTOR pathway, discussing key discoveries and recent insights related to the structure and regulation of mTOR complexes. Additionally, we highlight findings on the mechanisms by which mTOR is involved in protein synthesis and delve into mTOR-mediated processes occurring in MM. Finally, we summarize the progress and current challenges of drugs targeting mTOR complexes in MM.

Details

Language :
English
ISSN :
1478811X
Volume :
22
Issue :
1
Database :
Directory of Open Access Journals
Journal :
Cell Communication and Signaling
Publication Type :
Academic Journal
Accession number :
edsdoj.5bf627c82af4b75bb7d189ce17c47ad
Document Type :
article
Full Text :
https://doi.org/10.1186/s12964-024-01699-3