Researchers look for altered genes in lung cancer

José Pichel Andrés/ DICYT The departments of anatomic pathology, pulmonology, cardiothoracic surgery and oncology from the Hospital Universitario de Salamanca are a multidisciplinary team that aims to study new therapeutic targets in lung cancer, the leading cause of death in the Western world. Their end goal is to identify biomarkers in lung carcinomas that may be useful for more specific therapies.

In general terms, “diagnoses occur late and patients’ responses to treatment are poor”, as we were told by María Dolores Ludeña, a scientist of the Department of Anatomic Pathology of the Hospital Universitario de Salamanca, of the Department of Cell Biology and Pathology of the Universidad de Salamanca and head of this research area. That is why, “we are trying to carefully study its genetic changes using cutting-edge technology”, she adds.

Specifically, they are focused on mutations in epidermal growth factor receptor (EGFR), a gene on cell’s surface involved in intracellular communication, therefore, in signaling processes such as cell division; in the case of cancer cells, it may represent the extent of the tumor.

As EGFR undergoes mutations in some types of cancer, in lung carcinomas for instance, it has become a good therapeutic target to make drugs work on tumor cells. Nevertheless, “the problem is that a group of patients have very good responses, a second group do not respond at all and there is a third group that eventually develop resistance to treatment”, as the researcher states.

This resistance may be a consequence of “receptor’s activation in an area on the surface of a cell similar or close to EGFR”. That is why “we are trying to figure the reason out”, as Ludeña states. The end goal is to establish whether the activation of cellular pathways signaling the fundamental processes of cells, as cellular division, are related or not to the fact that EGFR undergoes some mutation and if therapies alter this process somehow.

The study is conducted with patients in the Hospital Universitario, a reference center for several provinces in Castilla y León: about a hundred lung cancer patients. “We are increasingly noticing changes in lung cancer cases and this information must be included in routine diagnosis”, she points out.

Tailored Treatments

“We aim to achieve tailored treatments; the major objective is to study all genetic changes in every patient and give them a specific therapy”, she states. For instance, it has been proved that MET is one of the genes involved, because “it activates in patients with a poor treatment response since there is another genetic change that we have not been able to localize”.

In this study they are using, with prior consent, patients’ samples coming from the leftover material used for diagnosis. At this point, they use in situ hybridization techniques in order to observe DNA changes.
The research team led by María Dolores Ludeña contributes in other research projects related to lung cancer, making good use of the scientific activity on this area in Salamanca. For example, the Centro de Invesigación del Cáncer (CIC), a cancer research center, is developing a project to study lung cancer stem cells. It is a basic research, but it is related to the clinical work of the Hospital Universitario. Furthermore, Ludeña’s team is also collaborating with an ambitious multidisciplinary project led by a chemical engineer called Eva Martín del Valle, its chief aim is to look for an alternative way to deliver drugs targeted to lung cancer tumor cells: using microcapsules to make the drug arrive to its destination.