Role of Different Metabolic Pathways on Development and Progression of Cancer

Dear Colleagues,

Metabolic pathways play a critical role in the development and progression of cancer. Cancer cells undergo various alterations in their metabolism in order to support their rapid growth, proliferation, and survival. These alterations are collectively referred to as cancer metabolism or the "Warburg effect," named after Otto Warburg, who observed enhanced glucose consumption and lactate production in cancer cells.

Some of the key metabolic pathways involved in cancer are as follows:

1. Glycolysis: Cancer cells often exhibit increased glucose uptake and rely heavily on glycolysis, even under aerobic conditions (the Warburg effect). Glycolysis breaks down glucose into pyruvate, producing a small quantity of ATP and NADH.
2. Pentose phosphate pathway (PPP): The PPP generates ribose-5-phosphate and NADPH, which are essential for nucleotide and lipid synthesis, respectively. NADPH also plays a crucial role in maintaining redox balance and protecting cancer cells from oxidative stress.
3. Tricarboxylic Acid (TCA) Cycle: Also known as the Krebs cycle or citric acid cycle, the TCA cycle generates ATP and provides intermediates for other biosynthetic pathways. Cancer cells may rewire the TCA cycle to support the synthesis of macromolecules required for rapid cell division.
4. Glutaminolysis: Glutamine is a vital for cancer cells. It is taken up by cancer cells and converted to glutamate via a series of reactions known as glutaminolysis. Glutamate can then be used to generate ATP, contribute to nucleotide synthesis, and produce antioxidants.
5. Lipid metabolism: Cancer cells require an adequate supply of lipids for membrane synthesis and signaling. They may upregulate de novo lipogenesis (synthesis of fatty acids) and increase lipid uptake from the environment.
6. Amino acid metabolism: Cancer cells have increased amino acid requirements to support protein synthesis and various metabolic pathways. They may upregulate amino acid transporters and enzymes involved in amino acid metabolism.
7. Mitochondrial metabolism: Cancer cells can exhibit alterations in mitochondrial function. In some cases, they rely less on oxidative phosphorylation (OXPHOS) and more on glycolysis for energy production (the Warburg effect). However, some cancers still retain functional mitochondria and rely on OXPHOS for ATP generation.

Understanding the metabolic pathways in cancer has led to the development of targeted therapies. For example, drugs that inhibit specific enzymes or transporters involved in cancer metabolism have been developed in order to selectively disrupt cancer cell growth and survival.

In this Special Issue, we will discuss the various critical metabolic pathways that occur in cancer progression. We will also discuss the therapeutic potential of targeting metabolic pathways in order to enhance overall survival and disease-free survival.

Prof. Dr. Parames C. Sil
Dr. Pritam Sadhukhan
Guest Editors

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• metabolic regulation in cancer
• metabolic reprogramming in cancer
• targeted therapy in cancer
• tumour metabolism