Development in Drug Repurposing for the Treatment of Acute Leukemia Complicating Metastatic Breast Cancer

Abstract

Despite many strategies being developed in drug discovery pipelines for the treatment and prevention, breast cancer is the major cause of cancer death observed in women globally. Nowadays, it has become the biggest concern for the World Health Organization due to the high-cost available treatment modalities and their side effects. The most common unmet challenge is arising due to drug resistance development as well as chemotherapy's side effect. The major drawback observed in breast cancer patients is acute leukemia due to prolonged chemotherapy and radiotherapy. To rectify this problem, many strategies have been introduced in the pharmaceutical field. Repurposing drugs in combination with computational techniques developed a new era in the field of drug discovery. Repurposing drugs, which include old drugs, with new applications introduces a novel beneficial approach that has been facilitated with advanced genomics, information computational biology as well as proteomics. Repurposing approach fastens the drug development process as well as provides cheaper medicines, more effectiveness, with fewer side effects. Treatment regimens for acute Leukemia increase the chances of patient survival. Most acute leukemia patients show downregulation of different proapoptotic factors, which are associated with cyclic AMP (cAMP). Gene expression profiles related to the increase in prosurvival cAMP activity are also apparent in patients with acute leukemia. To increase leukemia cells, different cAMP analogs have been used either by stimulation of cAMP production through transmembrane-associated adenylyl cyclases or by reducing cAMP degradation by phosphodiesterase activity inhibition. cAMP efflux inhibition stimulates differentiation of leukemia cells and cell growth arrest with apoptosis, which indicates that targeting the cAMP efflux gives huge chance in therapeutic development. The reduction of extracellular prosurvival signaling that takes place in malignant cells introduces multiple anticancer benefits. In this chapter, we will focus on several opportunities for targeting cyclic nucleotide transporters by drug repurposing.