Journal
CURRENT MEDICINAL CHEMISTRY
Volume 29, Issue 13, Pages 2290-2305Publisher
BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/0929867328666210910124319
Keywords
Drug resistance; hematological malignancies; tumor microenvironment; autophagy; endoplasmic reticulum stress; ECM
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The unique characteristics of the tumor microenvironment (TME) have a significant impact on the biological properties of various cancers, including hematological malignancies. TME factors can induce cancer invasion and protect against drug toxicity by inhibiting apoptosis and activating specific signaling pathways. The high self-renewal ability of the bone marrow facilitates the remodeling of TME and affects extracellular matrix components and signaling pathways.
The unique features of the tumor microenvironment (TME) govern the biological properties of many cancers, including hematological malignancies. TME factors can trigger an invasion and protect against drug cytotoxicity by inhibiting apoptosis and activating specific signaling pathways (e.g. NF-Kappa B). TME remodeling is facilitated due to the high self-renewal ability of the bone marrow. Progressing tumor cells can alter some extracellular matrix (ECM) components which act as a barrier to drug penetration in the TME. The initial progression of the cell cycle is controlled by the MAPK pathway (Raf/MEK/ERK) and Hippo pathway, while the final phase is regulated by the PI3K/Akt /mTOR and WNT pathways. This review summarizes the main signaling pathways involved in drug resistance (DR) and some mechanisms by which DR can occur in the bone marrow. The relationship between autophagy, endoplasmic reticulum stress, and cellular signaling pathways in DR and apoptosis is covered in the TME.
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