Understanding the biology of Vestibular Schwannom's mysterious cancer is key to personalized medicine

What is Vestibular Schwannoma?

Schwannoma of the vestibulo-cochlear nerve (Vestibular Schwannoma-VS) is a benign tumor of the central nervous system. It develops from myelin-producing Schwann cells surrounding the branches of the vestibulo-cochlear nerve. 95% of VS are single-sided tumors, referred to as sporadic tumors. In about 5% of patients, Schwannoma tumors of the vestibulocochlear nerve occur bilaterally, which is associated with a very rare genetic disease: neurofibromatosis Type II (NF2).  In recent years, due to the increasingly widespread availability of magnetic resonance imaging in neurological diagnostics, there has been an increase in VS detection, even at a very early, asymptomatic stage of the disease.

The most common symptom of VS is unilateral sensorineural hearing loss. It usually appears gradually, but some patients may experience a sudden significant deterioration in the hearing capabilities of the affected ear, which is called sudden sensorineural deafness. Other initial symptoms include tinnitus, dizziness and balance disorders. 

Despite the fact that VS is a benign tumor that does not metastasize, it can be dangerous to life due to its localization: in the central nervous system inside the patient's skull. When the tumor reaches a large size, it causes life-threatening symptoms of increased intracranial pressure, pressure on the brain stem and paralysis of the cranial nerves. Fortunately, this only applies to about 20% of patients diagnosed with VS. 

Methods of treating VS

Methods of treating Schwannoma of the vestibulo-cochlear nerve include microsurgical resection and targeted radiotherapy, currently carried out using the so-called Gamma Knife. At the Department of Otorhinolaryngology, Head and Neck Surgery UCK WUM, headed by Prof. Kazimierz Niemczyk, microsurgical VS resection operations have been carried out for over 20 years. 

Studies have shown, however, that in some patients these tumors are characterized by stable, very slow growth and can only be observed, without the need for invasive treatment.

Unfortunately, there are currently no known factors that would help identify potentially more aggressive, fast-growing tumors at an early, asymptomatic stage of the disease. Similarly, we do not yet know markers that would herald rapid hearing loss in a particular patient. All we know is that some patients experience a very rapid deterioration of hearing early in the disease, while others have stable hearing for a longer period of time. 

Understanding cancer biology

Understanding the molecular mechanisms of rapid growth and hearing damage by VS is very important because it can make it possible to identify patients who need to be intervened as early as possible to avoid possible complications of the disease. In the future, it may also contribute to the development of new methods of pharmacological treatment of VS in people who, for various reasons, cannot undergo surgery or experience tumor regrowth after treatment. 

In my scientific work, conducted by the Department of Otolaryngology, Head and Neck Surgery, I undertook research that will help explain and understand the biology of these fascinating tumors and select potential markers for their more aggressive variants. 

The results of pilot studies conducted at the clinic indicate that such biological markers of VS aggressiveness may include microRNA molecules (miRNAs). MiRNAs are small, non-coding RNA molecules, ranging in length from 21 to 23 nucleotides. They regulate gene expression by binding and silencing specific mRNA molecules. Both overexpression and reduced expression of specific microRNAs can lead to tumor development by silencing suppressor genes and increasing oncogene expression. Elevated or decreased levels of expression of various microRNA molecules have been shown in nervous system tumors such as meningiomas and gliomas, as well as VS. 

The latest research

In our latest scientific project, we made an analysis of the miRNA expression profile in tumor samples and cerebrospinal fluid samples taken from patients with small and large, clinically aggressive Schwannoma vestibulo-cochlear nerves. The study involved 20 patients operated on at our Clinic. Financing for the project was made possible thanks to the "Miniatura" grant of the National Science Centre and the statutory funds of the Medical University of Warsaw. We invited specialists from the Nencki Institute of Experimental Biology of the Polish Academy of Sciences to cooperate. The miRNA expression profile in the samples was analyzed using the latest and most accurate method called Next Generation Sequencing (NGS). 

We were able to show that small, stable and more aggressive Schwannoma of the vestibulo-cochlear nerve differed significantly in the expression of miRNA molecules. In large, clinically aggressive tumors, one of the issues we identified was increased expression of miRNA molecules involved in proteoglycan synthesis, fatty acid metabolism or interaction with the extracellular matrix. All these biological processes play an important role in the development and progression of cancer. 

In addition, we were able to identify specific types of miRNAs whose expression was associated with the deterioration in patients’ hearing, including small tumors. The next stage of our research will be the search for miRNA molecules identified by us in the serum of VS patients. The effectiveness of such a diagnostic method has already been confirmed in some types of cancer and is called "liquid biopsy". 

Future prospects

To sum up, apart from magnetic resonance imaging, we will perhaps also soon be able to offer our patients a simple blood test to help them decide whether to undergo surgical resection of the tumor, radiotherapy or maybe only observation for now. 

This type of personalized medicine is a noticeable and increasingly popular trend in cancer treatment around the world, and the Department of Otorhinolaryngology, Head and Neck Surgery UCK WUM certainly wants to fit into this modern trend.

Editor: Communication and Promotion Office of the MUW
Fot. Marcin Szumowski; Communication and Promotion Office of the MUW