Lung cancer accounts for the leading cause of cancer deaths worldwide. It is estimated that in 2018 more than two million people suffered from this disease and 1.8 died from it.

Despite the great advances made in recent decades in prevention (reducing tobacco consumption), early diagnosis and treatment, long-term survival deadline is much lower than in other types of cancer. This status has led the academic community to develop personalized therapies that can block the biological alteration of each patient or stimulate their immune system against the tumor.

A multi-center study, coordinated by the Cima and the Clínica Universidad de Navarrahas identified a molecule that not only predicts the prognosis of lung cancer patients but may open a pathway to development for future personalized therapies.

Patients with worse prognosis

"YES1 is a protein that regulates the proliferation of tumor cells and their ability to generate metastasis. It was known that the levels of this protein are elevated in several types of tumors such as colon cancer, liver cancer or melanoma. In this work we have shown that it is also increased in 15% of adenocarcinomas and 25% of lung squamous cell carcinomas, two of the most frequent types of lung cancer. In addition, this high expression is associated with a worse prognosis for patients, as it increases the probability of metastasis," explains Dr. Irati Garmendia, first author of this work developed in the Solid Tumors Program at Cima.

The findings have been published in the American Journal of Respiratory and Critical Care Medicine, which ranks second in the international ranking of scientific publications on respiratory medicine.

"With the data obtained we confirm that silencing this protein blocks the invasive capacity of tumor cells. This correlation is particularly important for guiding clinical trials aimed at inhibiting the activity of this family of proteins", says Dr. Luis Montuenga, researcher senior of the Solid Tumors Program at Cima, coordinator of the Respiratory Tract Program of CIBER Cancer (CIBERONC), and co-director of the study together with Dr. Jackeline Agorreta.

Target for future personalized therapies

The results obtained suggest that the YES1 protein is a viable target for the development of future personalized therapeutic strategies. "To confirm this hypothesis we have studied the effect of Dasatinib, a drug that is C for the treatment of patients with leukemias that, among other effects, inhibits YES1 activity. We have observed that treatment with Dasatinib selectively prevents tumor growth in lung tumors in which this protein is elevated. Our work sample that YES1 is a therapeutic target in lung cancer and can serve as a biomarker to identify patients who may benefit from treatment with Dasatinib or other drugs directed against YES1 or against members of its protein family," say Drs. Montuenga and Garmendia.

The researchers suggest that this therapeutic strategy could benefit patients for whom no targeted therapy is currently available. "Our efforts are now focused on reducing the side effects associated with this treatment and combining it with immunotherapy strategies that enhance the antitumor effect of this therapeutic approach."

Part of this work has been carried out with samples from 116 patients from the Clínica Universidad de Navarra and 222 patients from the MD Anderson Cancer Center at the University of Texas (USA). In addition, the partnership of the research center del Cáncer (CIC) of Salamanca, the Hospital Universitario Doce de Octubre, in Madrid, and the high school de research Sanitaria del Principado de Asturias, within the framework of the CIBER de Cáncer (CIBERONC). The Vall d'Hebron University Hospital and the high school de research Universitaria de Bellvitge, in Barcelona, have also participated. This research has been co-funded by the Scientific Foundation of the association Spanish Cancer Foundation (AECC), among other public and private entities.

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  Am J Respir Crit Care Med. 2019 Oct 1;200(7):888-899.