Application of targeted therapy in treatment of leukemia

Leukemias are broadly classified into two types: lymphoid/lymphoblastic and myeloid/myelogenous. Lymphoblastic leukemia leads to the formation of abnormal lymphocytes in the lymph nodes, spleen, tonsils, etc. In contrast, myelogenous leukemia involves bone marrow cells (precursors of red blood cells, white blood cells, and platelets). Among the types of leukemia, acute myeloid leukemia (AML) is the most common and aggressive form. Today, targeted therapies have gained significant attention due to their advantages over traditional treatment methods like chemotherapy and radiation therapy. These advantages include fewer side effects because they target a specific molecule in the cancer cell instead of attacking all cells in the body, as well as greater and faster efficacy. This approach specifically targets genes, proteins, and molecules that are only expressed in cancer cells and eliminates them without damaging healthy cells. These drugs may be prescribed alone or in combination with other treatments. The most common targeted therapy agents are monoclonal antibodies and small molecule inhibitors. Monoclonal antibodies may act through direct (i) or indirect (ii) mechanisms. Direct mechanisms (i) include: (a) Blocking ligand-receptor interactions by binding to soluble ligands/receptors or cell-bound ligands/receptors and inhibiting downstream signaling pathways, and (b) Binding to receptors and acting as agonists, leading to the activation of different signaling pathways. Indirect mechanisms (ii) are immune cell-mediated cytotoxicity mechanisms. Most monoclonal antibodies have an IgG۱ type Fc region that can activate effector cells like natural killer (NK) cells, leading to antibody-dependent cell-mediated cytotoxicity (ADCC). The Fc region can also activate macrophages and induce antibody-dependent phagocytosis (ADPH). This region is also capable of activating complement, leading to complement-dependent cytotoxicity (CDC). All these processes occur through the interaction of the Fc region with FcγR receptors on effector cells. Another type of these drugs are small molecules that, due to their low molecular weight, can penetrate the cell membrane and reach intracellular targets. Small molecule inhibitors inhibit the function of target proteins by binding to pockets on their surface. Researchers hope that over time, the efficacy of these drugs will increase and they will be able to treat various cancers. This review discusses the latest and most effective targeted drugs and their molecular mechanisms in the treatment of leukemia in general. Understanding the molecular pathways involved in this disease and identifying the molecular mechanisms of effective targeted drugs provides a basis for discovering new strategies for the diagnosis and treatment of this type of cancer.

کلیدواژه ها:

Leukemia ، targeted therapy ، cancer ، Immunotherapy