Multifaced Anticancer Potential of Doxorubicin: Spotlight on Breast Cancer

Abstract

Breast cancer is a leading cause of death among women worldwide due to its aggressive nature, early metastasis, and resistance to standard chemotherapy. Doxorubicin (DOX) is a potent anticancer drug and remains one of the most effective treatments for breast cancer. This review delves into the diverse anticancer attributes of DOX, encompassing its ability to induce DNA damage, provoke the production of reactive oxygen species, facilitate various mechanisms of cell death, and promote or enhance an anti-tumor immune response. Through an analysis of both monotherapy and combination therapy approaches, this review underscores the immense significance of DOX in contemporary breast cancer treatment. It also delves into the limitations of DOX-based therapies and provides insights into future perspectives for research and development in this field.

Keywords: Anticancer mechanism; Breast cancer; Combination therapy; Doxorubicin; Limitations; Nanoformulations.

Fig. 1.. DOX treatment causes DNA damage by the forming DOX-DNA adducts.

Fig. 2.. DDR pathway activation occurs due to DOX’s trapping of topoisomerase enzymes, leading to the formation of SSBs or DSBs and, finally, cell cycle arrest followed by cell death^[35].

Fig. 3.. DOX promotes the generation of ROS and programmed cell death by interacting with cardiolipin. This interaction leads to elevated ROS levels, causing harm to both nuclear and mitochondrial DNA. Moreover, DOX stimulates the extrinsic apoptosis pathway by enhancing the expression of FASL, binding to death receptors like TNFR1 and FAS, and activating CASP8 and effector caspases.

Fig. 4.. The mechanisms of resistance in breast cancer are complex and multifaceted, often arising due to genetic mutations, tumor heterogeneity, and the microenvironment. These factors can enable cancer cells to evade therapies such as hormonal treatments and chemotherapy, resulting in treatment failure. This figure illustrates the various types of resistance that have developed in breast cancer.