IIT Kanpur Researchers Identify Crucial Drug Target for Cancer and Respiratory Diseases

Researchers at IIT Kanpur have identified a crucial drug target receptor that could pave the way for advanced treatments for cancer and respiratory diseases.

IIT Kanpur Researchers Identify Crucial Drug Target for Cancer and Respiratory Diseases

The Indian Institute of Technology (IIT) Kanpur researchers have visualised the atomic structure of CXCR2, a key human receptor linked to cancer progression and respiratory disorders. This breakthrough, achieved by a team from the Department of Biological Sciences and Bioengineering, opens new avenues for developing targeted therapeutics. Their findings have been published in the prestigious journal Molecular Cell.

Leveraging advanced cryogenic-electron microscopy (cryo-EM), IIT Kanpur researchers have unveiled unprecedented insights into the lock-and-key mechanism that enables CXCR2 to recognize multiple chemokines. This breakthrough not only answers a fundamental question in biomedical science about how a common receptor binds and activates multiple chemokines but also paves the way for designing novel therapeutics using the receptor's structure as a template.

Chemokines are small signaling proteins essential for immune responses, directing immune cells to sites of infection and injury. They bind to specific receptors on cell membranes, triggering physiological reactions. Among these, CXCR2 stands out due to its association with various inflammatory diseases and cancers, including chronic obstructive pulmonary disease (COPD), asthma, atherosclerosis, and pancreatic cancer.

"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 team at IIT Kanpur includes Shirsha Saha, Saloni Sharma, Manisankar Ganguly, Nashrah Zaidi, Divyanshu Tiwari, Nabarun Roy, Nilanjana Banerjee, and Ramanuj Banerjee. The study also involved collaboration with researchers from the University of Tokyo, Japan, including Fumiya Sano, Hiroaki Akasaka, Takaaki Kobayashi, Yuzuru Itoh, Wataru Shihoya, and Osamu Nureki, as well as Andy Chevigne from the Luxembourg Institute of Health, Luxembourg.

This research was supported by grants from the DBT Wellcome Trust India Alliance, Science and Engineering Research Board (SERB), Indian Council of Medical Research (ICMR), and LADY TATA Memorial Trust. Building on this breakthrough, the team has initiated the development of novel therapeutics, including small molecules and antibodies targeting CXCR2. These candidates will undergo rigorous laboratory testing and animal studies, bringing IIT Kanpur closer to pioneering innovative treatments for cancer and respiratory diseases.

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