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IITK Researchers Unveils Key Receptor Structure for Cancer and Respiratory Treatments

The team successfully visualized the atomic structure of CXCR2, a crucial human receptor involved in the progression of cancer and respiratory diseases

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GPCR Lab. Image credit: By special arrangement

Researchers from the Department of Biological Sciences and Bioengineering at the Indian Institute of Technology (IIT) Kanpur have made a path breaking discovery that could pave the way for new treatments for cancer and respiratory diseases. The team successfully visualized the atomic structure of CXCR2, a crucial human receptor involved in the progression of these diseases. Their findings, published in the prestigious journal Molecular Cell, offer a new perspective on targeting this receptor for therapeutic intervention.

CXCR2 is a key receptor in the immune system, involved in directing immune cells to infection and injury sites through interaction with chemokines—small signaling proteins. CXCR2’s role in inflammatory disorders and cancers such as chronic obstructive pulmonary disease (COPD), asthma, atherosclerosis, and pancreatic cancer makes it a promising target for new drugs.

Using advanced cryogenic-electron microscopy (cryo-EM), the IIT Kanpur researchers captured unprecedented details of the receptor’s “lock-and-key” mechanism, shedding light on how CXCR2 interacts with multiple chemokines. This discovery addresses a fundamental question in biomedical science about how a single receptor can bind to various chemokines and trigger biological responses. The visualization also opens up opportunities for designing novel therapeutics.

“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, the 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. Their work also involved collaboration with experts from the University of Tokyo, Japan—Fumiya Sano, Hiroaki Akasaka, Takaaki Kobayashi, Yuzuru Itoh, Wataru Shihoya, and Osamu Nureki—along with Andy Chevigne from the Luxembourg Institute of Health.

This study was funded by 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 discovery, the IIT Kanpur team is now developing small molecules and antibodies aimed at targeting CXCR2. These therapeutics will undergo laboratory testing, followed by animal studies, bringing the team closer to offering innovative treatments for cancer and respiratory diseases. This achievement further underscores IIT Kanpur’s commitment to pioneering research that has the potential to revolutionize global healthcare and biomedical innovation.

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