UPES prof’s research aimed at minimising cancer reoccurrence

A research by Dr Dhruv Kumar, Senior Associate Professor at School of Health Sciences and Technology, UPES, strives to combine a new approach that involves inhibition of cancer and cancer stem cells through targeting metabolic and autophagic signalling, with traditional therapeutic methods to control the growth and progression of cancer

Dr Dhruv Kumar’s recent research into the role of autophagy and metabolism in cancer has yielded some interesting findings. According to the Senior Associate Professor at UPES School of Health Sciences and Technology, suppressing the altered metabolic and autophagic signalling in cancer and cancer stem cells can play an important role in minimising drug resistance and tumour reoccurrence in cancer patients.

Cancer usually develops when signalling pathways associated with normal cell cycle are disturbed because of genomic instability. Autophagy gets activated as a preventive force before genomic instability can lead to cell death.

Autophagy refers to the process by which a cell consumes its own damaged cellular organelles during starvation or periods of stress. It plays an important role in the survival of the cellular structure by modulating the metabolic switches. Autophagy controls the physiological and pathological processes at the cellular level which play a key role in the survival of cancer cells through the recycling of nutrients.

To sustain the metabolic function of the mitochondria and energy homeostasis – the process which regulates food intake and energy expenditure – starvation-induced autophagy reprocesses intracellular components into metabolic pathways, which are basically a linked series of chemical reactions occurring within a cell.

These metabolic and biosynthetic pathways reutilise and recycle the degraded ‘breakdown products’ that are released from lysosomes, which are the enzymes responsible for breaking down proteins, carbohydrates, and lipids.

Autophagy restricts tissue damage through the prevention of toxic accumulation of damaged cellular organelles and proteins, which helps inhibit cancer cell survival. As autophagy stimulation has great preventive and therapeutic value, this can be accomplished with periodic fasting.

This study enables us in bringing effective therapeutic strategy of combinatorial approaches to target metabolic as well as autophagic process in cancer patients. This combinatorial therapeutic approach can be more effective than the monotherapy-based strategies that are conventionally used for the treatment of cancer.

In addition, immunotherapy is increasingly involved in cancer treatment, and the fate of immune cells is also influenced by metabolism. The study of the interaction of immune cell metabolism with tumour metabolism and how these enzymes can be controlled by drugs can help design more effective immune therapies against cancer progression.

Combinatorial therapeutic approach through targeting autophagy and metabolism in a tumour will have a more effective therapeutic effect compared to monotherapy, which will certainly increase the survival of cancer patients.

“In the last two decades, we have clearly understood the process of reprogramming of metabolic switches of cancer cells for their survival and growth in which autophagy plays an important role. One such metabolic effect in cancer cells is the ‘Warburg phenomenon’, where cancer cells utilise a hundred times more glucose than normal cells because of impaired mitochondrial activity,” Dr Dhruv says.

“We have previously demonstrated that prolonged activation or suppression of autophagy in cancer cells leads to apoptosis and finally cell death. Our recent study suggests that blocking of glycolysis leads to the immediate death of cancer cells,” he adds.

Cancer is now responsible for more deaths around the world than cardiac arrest. Though solid tumours are highly heterogeneous, the main mechanism behind the growth and progression of cancer cells is altered metabolic states (mainly glycolysis) which are closely associated with the autophagic modulation in cancer cells. Targeting autophagy and altered metabolic switches in cancer cells could be an important therapeutic approach, in combination with conventional chemo and radiotherapy.