IIT Kanpur Identifies Key Drug Target for Cancer, Respiratory Diseases

Indian Institute of Technology (IIT) Kanpur scientists have mapped the atomic structure of CXCR2, a key human receptor associated with cancer and respiratory diseases. This historic achievement by the Department of Biological Sciences and Bioengineering unlocks new avenues for the development of targeted therapies. The research has been published in a top-tier journal Molecular Cell.

Scientists discovered how CXCR2 binds to different chemokines cocktail of small signalling molecules that have an important role to play in the immune system using high-end cryogenic-electron microscopy (cryo-EM). The latest finding sheds light on the age-old biomedical science question regarding the 'lock-and-key' mechanism of receptor binding and activation of a host of chemokines.

Chemokines are small signaling proteins found to be crucial in immune responses, directing the immune cells to sites of infection and injury. They bind to specific receptors on cell membranes and stimulate physiological reactions. CXCR2 is implicated in several inflammatory diseases and cancers, including chronic obstructive pulmonary disease (COPD), asthma, atherosclerosis, and pancreatic cancer. Their structural anoscope creates a basis for a novel therapeutic option for more recent mutant viruses using the receptor as a model.

"Our findings provide a molecular blueprint for designing next-generation therapeutics that can precisely target CXCR2 and potentially reduce its role in cancer and respiratory diseases. By visualizing this receptor in its active state, we now have the opportunity to develop highly specific inhibitors that can disrupt its function, potentially leading to significant advancements in treatment strategies," said Professor Arun Kumar Shukla, lead investigator of the study at IIT Kanpur.

The research was funded by the DBT Wellcome Trust India Alliance, Science and Engineering Research Board (SERB), Indian Council of Medical Research, and LADY TATA Memorial Trust. The IIT Kanpur researchers collaborated with scientists from the University of Tokyo, Japan, and Luxembourg Institute of Health, Luxembourg.

Researchers are now turning their attention to CXCR2 as a new target for small-molecule and monoclonal antibody therapeutics. In the laboratory and in animal models, they will now need to test candidate compounds thoroughly as yet another step on the road to new agents for the treatment of cancer and other disorders of the lungs.