Repurposing of Metabolic Drugs and Mitochondrial Modulators as an Emerging Class of Cancer Therapeutics with a Special Focus on Breast Cancer

116 Pages Posted: 24 May 2022

See all articles by Hamendra Singh Singh Parmar

Hamendra Singh Singh Parmar

Devi Ahilya University (DAVV)

Versha Tripathi

Devi Ahilya University (DAVV)

Pooja Jaiswal

Devi Ahilya University (DAVV)

Khageshwar Sahu

Raja Ramanna Centre for Advanced Technology

Shovan Kumar Majumder

Raja Ramanna Centre for Advanced Technology

Dharmendra Kashyap

Indian Institute of Technology (IIT), Indore

Amit Kumar Dixit

Central Council for Research in Ayurvedic Sciences

Hem Chandra Jha

Indian Institute of Technology (IIT), Indore

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.

Summary: 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.

Note:
Funding Information: The work was supported by the CSIR-JRF fellowships to Ms. Pooja Jaiswal (File No. 09/301 (0137)/2019-EMR-I) and Ms. VershaTripathi (09/301 (0138)/2019-EMR-I). We also acknowledge the India-Belarus joint project (DST/ INT/BLR/P-24/2019) funded by Department of Science and Technology, New Delhi, sanctioned to Dr. Hamendra Singh Parmar.

Declaration of Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Keywords: AICAR, Tigecycline, Cordycepin, Mitochondrial redox modulators, Statins, Fibrates.

Suggested Citation

Parmar, Hamendra Singh Singh and Tripathi, Versha and Jaiswal, Pooja and Sahu, Khageshwar and Majumder, Shovan Kumar and Kashyap, Dharmendra and Dixit, Amit Kumar and Jha, Hem Chandra, Repurposing of Metabolic Drugs and Mitochondrial Modulators as an Emerging Class of Cancer Therapeutics with a Special Focus on Breast Cancer. Available at SSRN: https://ssrn.com/abstract=4118479 or http://dx.doi.org/10.2139/ssrn.4118479

Hamendra Singh Singh Parmar (Contact Author)

Devi Ahilya University (DAVV) ( email )

Versha Tripathi

Devi Ahilya University (DAVV) ( email )

Pooja Jaiswal

Devi Ahilya University (DAVV) ( email )

Khageshwar Sahu

Raja Ramanna Centre for Advanced Technology ( email )

Indore
India

Shovan Kumar Majumder

Raja Ramanna Centre for Advanced Technology ( email )

Indore
India

Dharmendra Kashyap

Indian Institute of Technology (IIT), Indore ( email )

M-block
IIT Indore
Indore, 452017
India

Amit Kumar Dixit

Central Council for Research in Ayurvedic Sciences ( email )

JLNBCH Bhawan
61-65 Institutional Area, Opp Janakpuri D Block
New Delhi, 110058
India

Hem Chandra Jha

Indian Institute of Technology (IIT), Indore ( email )

M-block
IIT Indore
Indore, 452017
India

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