Repurposing of metabolic drugs and mitochondrial modulators as an emerging class of cancer therapeutics with a special focus on breast cancer

Abstract

Background: As per facts sheet of WHO, cancer is a leading cause of mortality worldwide accounting nearly 10 million deaths in 2020. However, breast, lung, colon and rectum, prostate, skin and stomach cancers are the six most prevailing cancer across the globe. Out of the aforesaid cancers, breast cancer is the most commonly diagnosed cancer worldwide with 2.26 million cases in 2020. Metabolic alterations have been found to be associated with most of the cancers, suggesting that both loss of mitochondrial functioning (Warburg metabolism) as well as gain of mitochondrial functioning (OXPHOS) are contributing factor for cancer progression, invasion and metastasis. Here it is noteworthy that cancer is a heterogeneous mass of the cells and different cell types are having different tactics due to difference in tumor microenvironment, clonal selection, clonal evolution and cancer stem cell formation which resultantly affects the overall therapeutic response of the cancer therapies, chemo-resistance, radio-resistance, cancer stem cell formation, angiogenesis, migratory potential, invasion-metastasis cascade etc. Cancer cells are having a great metabolic plasticity which supports their survival, proliferation, invasion, metastasis and relapse. Variety of metabolic drugs are already in clinical practice for various metabolic disorders and are known for their proven safety and efficacy track record since decades and they have been reported for pleitropic influence on mitochondrial metabolism as well as biogenesis. Similarly, some other emerging pro- and anti-oxidative drugs for mitochondrial reactive oxygen species are also known to modulate mitochondrial functioning by various means. Therefore, present review sheds light on the potential of metabolic drugs and mitochondrial modulators on cancer pathologies and their underlying molecular mechanisms through which they may improve clinical outcomes and prognosis of cancer patients by many folds. © 2022 The Authors