They identify new molecular pathways that improve the approach to lung cancer

They identify new molecular pathways that improve the approach to lung cancer

Jackeline Agorreta, Irati Garmendia and Luis Montuenga, research coordinators. / Manuel Castells

Lung cancer is the leading cause of death from this disease in the world. It is estimated that in 2018 more than two million people suffered from this disease and 1.8 died from it. In spite of the great advances of the last decades in prevention (reducing tobacco consumption), early diagnosis and treatment, long-term survival is much lower than in other types of cancer.

This situation has guided the scientific community to develop personalized therapies that can block the biological alteration of each patient or that stimulate their immune system against the tumor.

A multicenter study, coordinated by the Center for Applied Medical Research (CIMA) and the Clínica Universidad de Navarra, has identified a molecule that not only predicts the prognosis of these patients but can open a path to the development of future personalized therapies.

“YES1 is a protein that regulates the proliferation of tumor cells and their ability to generate metastases. It is known that levels of this protein are elevated in several types of tumors such as colon, liver or melanoma cancer. In this work we have shown that it also increases in 15% of adenocarcinomas and in 25% of squamous carcinomas of the lung, two of the most frequent types of lung cancer. In addition, this high expression is associated with a worse prognosis since it increases the probability of metastasis, ”explains Irati Garmendia, first author of this work.

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 especially important to guide clinical trials aimed at inhibiting the activity of this family of proteins, ”says Luis Montuenga, researcher at Cima and the Center for Biomedical Research in Cancer Network (CIBERONC) and co-director of the study together with Jackeline Agorreta.

Diana 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, the authors studied the effect of dasatinib, a drug that is approved for the treatment of patients with leukemia that, among other effects, inhibits the activity of YES1. “We have observed that Dasatinib treatment selectively prevents tumor growth in lung tumors in which this protein is elevated.

Our work shows that YES1 is a therapeutic target in lung cancer and can serve as a biomarker to identify patients who can benefit from treatment with Dasatinib or other drugs directed against YES1 or against members of their protein family, ”Montuenga and Garmendia point out.

The researchers suggest that this therapeutic strategy could benefit patients who currently do not have any targeted therapy. “Our efforts are now focused on reducing the side effects associated with this treatment and combining it with immunotherapy strategies that improve the antitumor effect of this therapeutic approach.”Part of this work has been carried out with samples from 116 patients of the University of Navarra Clinic and 222 patients of the MD Anderson Cancer Center of the University of Texas (USA). In addition, it has had the collaboration of the Cancer Research Center (CIC) of Salamanca, the Doce de Octubre University Hospital in Madrid, and the Health Research Institute of the Principality of Asturias, within the framework of the CIBER de Cáncer (CIBERONC) . The Vall d’Hebron University Hospital and the Bellvitge University Research Institute in Barcelona have also participated.

Bibliographic reference:

Am J Respir Crit Care Med. 2019 Oct 1; 200 (7): 888-899.This research has been co-financed by the Scientific Foundation of the Spanish Association Against Cancer (AECC), among other public and private entities.


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