Researchers at Cima University of Navarra have uncovered new mechanisms involved in the development of pancreatic and lung cancer. The study, carried out with experimental models, confirms the role of a small molecule (the microRNA miR181ab1) in the training and evolution of these tumors.

KRAS is one of the most frequent oncogenes in human cancer. Approximately 30% and 90% of patients with lung and pancreatic cancer, respectively, have mutations in this oncogene. "Despite its clear role in cancer in general, and in these two types of tumors in particular, to date there are no effective therapies approved for clinical use in oncology patients. Therefore, it is essential to know the abnormal mechanisms activated by the KRAS oncogene, so that we can develop therapeutic strategies for these patients", explains Dr. Silve Vicent, researcher of the Solid Tumors Program at Cima, member of CIBERONC and director of this study.

Scientists at Cima have developed a novel work that integrates genetically modified mouse models, 3D cell cultures derived from animal models and human cell lines, and in vitro models, as well as clinical data from patient series of both tumor types. "Our programs of study reveals that the miR181ab1 microRNA plays a crucial role in the initiation of pancreatic cancer and lung cancer. Moreover, more relevantly, its knockdown in tumors of both types of cancer in mice (mimicking the treatment that would be applied in patients) generates a very potent antitumor effect."

This research, published in the scientific journal Journal of Cinical Investigation, has been carried out at partnership with the group of Dr. Alejandro Sweet-Cordero of the University of California, San Francisco (USA).

Therapeutic application

According to Dr. Vicent, "one of the most relevant conclusions of this work is its therapeutic application. Specifically, we have confirmed that if we combine the elimination of this molecule and the administration of a drug already C for hematological tumors, we obtain a greater antitumor response in lung cancer". Therefore, this work provides the basis for the development of future strategies to inhibit miR181ab1 as a potential therapy in these tumors.

Currently, researchers at Cima are seeking funding to study the implications of the joint inhibition of this microRNA and immune system modulators in lung and pancreatic tumors. "Our final goal is to find new strategies to boost the antitumor response of the immune system in both tumor types, since current treatments have a very limited effect," concludes Dr. Vicent.

The work, developed in the framework of the high school of research Sanitaria de Navarra (IdiSNA), has received funding from various public and private institutions, such as the Ministry of Economics and Competitiveness, the Worldwide Cancer Foundation, the CajaNavarra Foundation and "la Caixa" Foundation, the scholarship María Eugenia Burgos de la Iglesia and the association of Novelda of financial aid to people with cancer.

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  J Clin Invest. 2020 Apr 1;130(4):1879-1895.