The Emerging Role of Monocarboxylate Transporter-1 in Cancer: Overview and Therapeutic Opportunities
- Pp. 23-42 (20)Gouthami Thumma, Kiran Gangarapu, Anvesh Jallapally and Anil Kumar Mondru
Cancer has become a global pandemic that accounts for almost 13% more deaths than any other infectious diseases. According to the World Health Organization (WHO), projections of cancer prevalence is expected to raise to 21.7 million cases and 13 million deaths by 2030. Over the last 10 years, considerable improvements have been achieved in the management of cancer, and yet the disease remains incurable. There is an urgent need to develop therapeutic agents with novel drug combinations to achieve better efficacy, and reduce the possibility of relapse and drug resistance. Cancer progression, development of metastases represents the major characteristic feature for solid tumours in the presence of hypoxia. Under hypoxic conditions, cancer cells consume glucose that is metabolized to lactate, and then exported into the extracellular milieu, contributing to the acidic microenvironment. In this context, monocarboxylate transporters (MCTs) will play a significant role in maintaining the hyper-glycolytic acid resistant phenotype of cancer, allowing the maintenance of the high glycolytic rates by performing lactate efflux, and pH regulation by the cotransport of protons. Hence, MCTs constitute attractive adjuvant targets for cancer therapy. In this chapter, we review cancer biology from the perspective of the lactate shuttle concept which mainly focuses on the development of MCT inhibitors and highlights current and potential future therapeutic approaches that supports the notion of targeting lactate metabolism with novel anticancer agents.