Editorial Volume 20 Issue 1 - October 2021 DOI: 10.19080/CTOIJ.2021.20.556026 Cancer Ther Oncol Int J Copyright © All rights are reserved by Nahla A M Hamed Targeting Myeloma Microenvironment as Antitumor Strategy Nahla A M Hamed* Internal Medicine Department (Hematology Unit), Faculty of Medicine, Alexandria University, Alexandria, Egypt Submission: October 04, 2021; Published: October 19, 2021 *Corresponding author: Nahla A M Hamed, Internal Medicine Department (Hematology Unit), Faculty of Medicine, Alexandria University, Alexandria, Egypt Cancer Ther Oncol Int J 20(1): CTOIJ.MS.ID.556026 (2021) 001 Cancer Therapy & Oncology International Journal ISSN: 2473-554X Introduction Multiple myeloma (MM) is a hematological malignancy characterized by growth and expansion of clonal plasma cells almost exclusively in the bone marrow (BM) [1]. Multiple osteolytic lesions are present in most myeloma patients [2]. These lesions represent osteolytic bone metastasis rather than bone marrow infiltration, as in other hematological malignancies [3]. MM is still a fatal malignancy despite the great advance in its treatment. This is mainly attributed to the permissive role of the BM microenvironment in differentiation, proliferation, migration, survival, and drug resistance of the malignant plasma cells [1]. Malignant plasma cell traficking and MM develop- ment Malignant plasma cells reach the BM niche through sinusoids, where it proliferates favored by the tumor microenvironment (TME) [2]. The progression and ‘metastasis’ of MM occurs through trafficking of malignant plasma cells continuously in and out of the BM to reach new BM sites [2]. Occasionally, malignant plasma cells egress from the BM to reach different organs causing extramedullary disease [4]. BM Microenvironment The bone marrow microenvironment is also known as the bone marrow niche. It consists of a cellular and non-cellular component [3]. Each component exerts different effects on malignant plasma cells progression and both components work synergistically [1]. i. The cellular component is subdivided into hematopoietic cells (myeloid-derived suppressor cells, T lymphocytes, B lymphocytes, NK cells, regulatory T cells and osteoclasts) and non-hematopoietic cells (bone marrow stromal cells, fibroblasts, osteoblasts, endothelial cells, and blood vessels) [1]. ii. The non-cellular component includes the extracellular matrix, oxygen concentration, as well as cytokines, growth factors, and chemokines produced and/or affected by the cellular component of the BM microenvironment [1]. Abstract Despite the great advance in myeloma treatment, it still considered a fatal disease due to the permissive role played by the bone marrow (BM) microenvironment in disease establishment and progression. Understanding mechanisms of malignant plasma cells trafficking into and out of the BM may lead to improvement in prevention of disease progression and in overcoming drug resistance. The trafficking and homing of malignant plasma cells to the BM are regulated by soluble factors, and by direct interaction between plasma cells and bone marrow-resident cells. In the BM niche, malignant plasma cells reprogram the local BM microenvironment to induce malignant plasma cells retention, proliferation and drug resistance. Extramedullary disease develops in some patients, as a result of changes in plasma cells chemokine receptor expression or function and their independency of survival factors in BM niche. Furthermore, malignant plasma cells can prepare premetastatic niches for tumor dissemination in distant bone regions, by releasing cytokines, growth factors, and exosomes that remodel the extracellular matrix at these new sites. Abbreviations: BM: Bone Marrow; BMSC: BM Mesenchymal Stromal Cells; MM: Multiple Myeloma; TME: Tumor Microenvironment; CXCR: Chemokine Receptor; PDE: Phosphodiesterase; VEGF: Vascular Endothelial Growth Factor; SDF: Stromal Cell–Derived Factor; BAFF: B-cell Activating Factor; HSP: Heat-Shock Proteins.