In the month of brain cancer awareness, we tell you about the work of two IBioBA teams that seek to understand how brain tumors originate and evolve.
Basic science work is key to understanding this complex disease and developing new strategies to tackle it.
Every May, the world dedicates a space to reflect on and raise awareness of brain cancer, a complex and still difficult-to-treat disease. But it is also an opportunity to highlight the fundamental role played by basic science: that research that seeks to understand how the body works (and what happens when something goes wrong) is the foundation on which future treatments are built.
Cancer is, in simple terms, the result of abnormal behavior of our own cells: they multiply uncontrollably, invade other tissues and refuse to stop. A disease that can start in any part of the human body and usually occurs when the normal process of cell division is damaged, causing cells to multiply when they should not. In the case of brain cancer, the problem appears within the central nervous system, either because the cancer cells originate there (primary tumors) or because they arrive from other organs (secondary or metastatic tumors).
These abnormal masses can grow at different speeds, have a greater or lesser capacity to damage tissues, and generate very diverse symptoms, depending on their size and location. For this reason, it is essential to know them in depth in order to be able to combat them. At the Institute of Biomedicine of Buenos Aires (IBioBA, CONICET – Max Planck), two groups are dedicated to studying different tumors that lodge in the brain: the one led by Dr. Carolina Perez-Castro and the one led by Dr. Eduardo Arzt.
Researching the most aggressive tumors
The “Tumor stem cells and cellular plasticity” group, led by Perez-Castro, has been researching gliomas and glioblastomas (GBM), malignant and very aggressive tumors of the nervous system, for more than 15 years. Glioblastoma, in particular, is the most frequent and devastating primary malignant tumor of the central nervous system. It affects about 3 persons per 100,000 and its evolution is rapid and invasive.
Current treatments – surgery, chemotherapy and radiotherapy – help to contain the disease, but have failed to significantly improve patient survival in recent decades. That’s why basic research remains essential. “Clinical trials and targeted therapies are being conducted to look for new alternatives, through a joint effort between basic and clinical research”, says Perez-Castro.
His team seeks to understand how these tumor cells can change their shape and behavior, a phenomenon known as cellular plasticity. This ability to “adapt” is what makes them more resistant and aggressive. In this line, they are studying the role of genes that contribute to tumor sustainability, with the aim of modulating them to slow down their growth and metastatic capacity.
In previous studies, the group identified, together with FLENI colleagues, that a protein called KANSL2 plays an important role in the formation of these tumors. Now, their research, together with national and international collaborators, aims to deepen the function of KANSL2 in the biology of these tumors: “Knowing how this protein affects the expression of genes involved in the growth, proliferation and behavior of these aggressive tumors will allow the development of new therapeutic avenues”, adds Nicolás Budnik, a doctoral fellow in the group. In addition, together with Hernán Grecco’s team at the Instituto de Física de Buenos Aires (IFIBA, UBA-CONICET), they developed a tool to study and predict the collective and migratory behavior of three-dimensional tumor colonies, which could be used to explore the mechanism of action of certain drugs for clinical use.
Pituitary tumors: the “good guys” in the movie
The other IBioBA team, led by Dr. Eduardo Arzt, studies a different type of brain tumors: those originating in the pituitary gland, a key gland of the neuroendocrine system. “These tumors are one of the most frequent types of brain tumors in the population”, Arzt says. And although they have special characteristics that make them usually benign, i.e., they do not spread, they can alter important body functions. “We have been studying these tumors for more than 20 years to understand why they have low malignancy, in order to understand the processes of other tumor types, and also to contribute to their treatment, as we have already done with one of the subtypes of pituitary tumors (Cushing’s)”, adds Arzt.
In the team, for example, they study the role of the RSUME gene -a protein identified by the group in 2007- in pituitary tumor processes (in which they found that it interacts with and regulates an important protein in the cell cycle, PTTG securin). Their goal is to study the molecular characteristics of this type of tumors to better understand their behavior and, in the long term, contribute to improve diagnosis and treatment options. “We want to gain in-depth knowledge of these mechanisms in order to find new ways of intervening in the tumor process”, says Mariana Fuertes, a researcher on the team.
Recently, they identified in experimental models a molecular mechanism that helps to explain why these tumors usually grow slowly and present a benign behavior: “In particular, we discovered that the elimination of a key protein, interleukin-6, can transform these cells into malignant forms, which opens new possibilities to understand their progression and explore more effective therapeutic strategies”, comments Florencia Herbstein, postdoctoral fellow.
Raising awareness of these tumors and the importance of multidisciplinary basic research is a priority in order to attack these diseases. Understanding how brain tumors are born, grow and evolve not only helps to explain the disease: it also makes it possible to imagine new therapies. Although this research does not yet have immediate clinical application, they are fundamental steps on the road to more effective solutions. Knowledge opens doors to new treatment opportunities.
In this awareness month, recognizing the work of those who research in basic science is also a way to bring us closer to a future with more and better answers to brain cancer.