Inhibition of DNA damage response pathway using combination of DDR pathway inhibitors and radiation in treatment of acute lymphoblastic leukemia cells

An alarming increase in acute lymphoblastic leukemia cases among children and adults has attracted the attention of researchers to discover new therapeutic strategies with a better prognosis. In cancer cells, the DNA damage response (DDR) pathway elements have been recognized to protect tumor cells from various stresses and cause tumor progression; targeting these DDR members is an attractive strategy for treatment of cancers. The inhibition of the DDR pathway in cancer cells for the treatment of cancers has recently been introduced. Hence, effective treatment strategies are needed for this purpose. Chemotherapy in combination with radiotherapy is considered a potential therapeutic strategy for acute leukemia. This review aims to assess the synergistic effects of these inhibitors with irradiation for the treatment of leukemia. Lay abstract Acute lymphoblastic leukemia (ALL) is a blood malignancy that is caused by the high proliferation of lymphoid precursors in bone marrow and peripheral blood, and it is one of the common malignancies among children and adults. Novel therapeutic strategies are increasingly being studied to suppress cancer cells. DNA damage response pathways have developed in cancer cells that protect tumor cells from chemotherapy and radiotherapy and cause relapse and treatment failure. Effective drugs in ALL treatment can suppress cancer cells through several mechanisms, such as inducing DNA damage in cancer cells. However, due to the active repair systems in cancer cells, treatment may fail. Recently, the inhibition of these repair pathways and the combination of DNA damage response pathway inhibitors with chemotherapy and radiotherapy in cancer treatment have been studied. The purpose of this review is to outline the synergistic effects of DNA damage response pathway inhibitors and radiation in the death of leukemic cells.

Automated summary

In response to the alarming increase in acute lymphoblastic leukemia cases, researchers are investigating new therapeutic strategies targeting DNA damage response pathways to overcome resistance to chemotherapy and radiotherapy. This review aims to evaluate the synergistic effects of DNA damage response pathway inhibitors with radiation in the treatment of leukemia.