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Role of the Bone Marrow Microenvironment in Drug Resistance of Hematological Malignances Publisher Pubmed



Hosseini A1 ; Hamblin MR2 ; Mirzaei H3, 4 ; Mirzaei HR5
Authors
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Authors Affiliations
  1. 1. Laboratory Hematology and Blood Banking, Tehran University of Medical Sciences, Tehran, Iran
  2. 2. Laser Research Centre, Faculty of Health Science, University of Johannesburg, Doornfontein, 2028, South Africa
  3. 3. Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran
  4. 4. Student Research Committee, Kashan University of Medical Sciences, Kashan, Iran
  5. 5. Department of Medical Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

Source: Current Medicinal Chemistry Published:2022


Abstract

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-ΚB). 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. © 2022 Bentham Science Publishers.
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