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Researchers at Cima University of Navarra find the 'Achilles' heel' of lung cancer

Scientists make this tumor respond to immunotherapy by inhibiting a subject protein involved in the development tumor.

/From left to right: Cima researchers Andrea Pasquier, Mirari Echepare, Karmele Valencia, Luis Montuenga and Álvaro Teijeira.

15 | 11 | 2022

Researchers at Cima University of Navarra have succeeded in making immunotherapy-resistant lung tumors respond to treatment. The scientists have discovered that the 'Achilles heel' of this tumor lies in the inhibition of DSTYK, a protein subject involved in tumor development . This protein is altered in a high percentage of patients, which makes it a new therapeutic target for the treatment of this disease, the leading cause of cancer-related death in the world.

This study recognizes for the first time the dependence between the DSTYK protein and lung cancer, a finding that "allows us to identify those patients who will not respond to immunotherapy," says Karmele Valencia, researcher in the Solid Tumors Program at Cima and first author of article. In addition, "prioritizing this new target would lay the groundwork for the development of drugs and clinical trials that can expand the percentage of patients who benefit from immunotherapy-based treatments," says Luis Montuenga, also researcher of the Solid Tumors Program at Cima and researcher lead author of the study.

This work is published in the latest issue of the Journal of Experimental Medicine. Researchers from the University of Navarra, the University of Cologne and the Vall d'Hebron Oncology Center collaborated in the study. Clínica Universidad de NavarraUniversity of Navarra, the University of Cologne and high school of Oncology Vall d'Hebron. Several of the researchers of this work belong to the research center Biomedica en network en Cáncer (CIBERONC) and to the high school de research Sanitaria de Navarra (IdiSNA).

Collapse tumor cells and boost cell-mediated immunity

Lung cancer is the leading cause of cancer-related death in the world. According to the latest report of the Spanish Society of Medical Oncology, this cancer subject is manager of 18% of cancer deaths worldwide. This same report indicates that in 2022 in Spain 30,948 new cases of this disease will be diagnosed. In the last decade, lung cancer survival has improved thanks to prevention strategies, early detection and improved therapeutic strategies based on personalized medicine and immunotherapy. However, there are still patients who do not respond to these therapies.

In recent years, a promising treatment for lung cancer has been proposed that involves modulating autophagy, "a process by which cells destroy their own contents in order to survive. Autophagy has been shown to play a central role in tumor training and progression, since once the tumor is established, autophagy feeds and supports cancer cell growth and contributes to drug resistance by influencing tumor immune evasion," explains Montuenga.

"In our study we have shown that the DSTYK protein is a central regulator of autophagy. Inhibiting this protein collapses the autophagy process and increases the sensitivity of tumor cells to immune-based therapies. This finding supports the relevance of this protein as a therapeutic target to advance personalized medicine efforts for the treatment of lung cancer," explains Valencia.

→ reference letter literature:
DSTYK inhibition increases the sensitivity of lung cancer cells to T cell-mediated cytotoxicity. Valencia K et al.,.J Exp Med. 2022 Dec 5;219(12):e20220726. doi: 10.1084/jem.20220726.