Did you know that cancer cells load up on sugar from your body? As they multiply rapidly, they are deprived of Oxygen, thus differentiating between cancerous tumours and normal tissue. This state, called, hypoxia causes the failure of popular cancer treatments like chemotherapy and radiology. Researchers are working on novel therapies for resistant tumours using these very cellular properties to treat the world’s most dangerous disease.
“Hypoxia can be a direct cause of therapeutic failure as certain drugs and radiation require oxygen for maximal effect. Hypoxia can also affect indirectly as it controls the expression of several genes promoting survival of cancer cells,” says Dr. Kapil Juvale, Assistant Professor at Shobhaben Pratapbhai patel School of Pharmacy & Technology Management(SPPSPTM) of NMIMS University. He has been awarded Science & Engineering Research Board (SERB) grant by the Department of Science and Technology of Government of India.
Juvale, like many researchers worldwide, is working on mechanisms that alter the cellular metabolism of cancer cells. Apart from being the main cause of death worldwide, claiming over 8.2 million lives, cancer has always been a challenge to drug researchers due to extreme side-effects. “We definitely need better and specific drugs, which are less toxic and more potent. The research project chosen (by him) will help to identify new drug targets and therapeutic agents,” he said.
Monocarboxylate transporter inhibitors, as new therapy:
In rapidly growing cancer cells, hypoxia stimulates glycolytic metabolism (increased consumption of glucose). This leads to generation of large amounts of lactic and carbonic acids. Monocarboxylate transporters (MCTs) are key regulators of intracellular lactate and pH, required for the survival of cancer cells.
Monocarboxylate transporter inhibitors, especially, small molecule inhibitors of MCT1 are known to have minimal side-effects. These inhibitors work in two ways. They can ensure that aerobic cells (oxygenated tumour cells) to consume more glucose, starving away hypoxic cancer cells to death. The second way is to alter the pH of tumour cells (by inhibition of MCT4), killing them by acidification. Juvale is researching on designing inhibitors which have synergistic inhibitory effect both ways.
Dual inhibitors (MCT1 and MCT4) are newly recognized and identified as attractive targets for therapy, and is still in its nascent stage. “So far, only few compounds such as AZD-3965, AR-C155858 and naturally occurring flavonoids (like the one present in green tea, grapefruit and tomato skins) have been found to be inhibitors of MCT1. The main objective of this study is to identify new potent and selective inhibitors of these lactate transporters as novel anti-cancer therapy,” said Juvale, who intends to design drugs from them.
Juvale’s research in in medicinal chemistry at the University of Bonn, Germany helped him gain interest in answering biological questions using small molecular tools. “The early career research award by the SERB will allow me to attain this goal by getting support to continue my research at the NMIMS Pharmacy School. It will help me to start my research career and build myself as an independent researcher without financial constraints,” he said.
NMIMS SPP School of Pharmacy & Technology Management in Mumbai, has been fostering research amongst its students and faculty. The schools faculty, which is well-known for its patent, has published over 150 articles in national and international publications. The range of topics include medicinal properties of turmeric to use of functional nanosponges for antibacterials.
Dr. Kapil Juvale is currently working as an Assistant Professor in Pharmaceutical Chemistry at the NMIMS SPP School of Pharmacy & Technology Management(SPPSPTM). He has extensive research experience in the field of medicinal chemistry. Before joining SPPSPTM he worked as a postdoctoral fellow at the IIT Gandhinagar, where his research was focused on the identification of new drug target for treating infectious diseases. As a German Academic Exchange Service (DAAD) fellow and a doctoral researcher at the University of Bonn, his research work involved synthesis and biological studies of small molecule inhibitors of ABC transporters responsible for the multidrug resistance in cancer. His interdisciplinary research involves synthetic chemistry, medicinal chemistry and cell biology.