Circulating tumor cells as a non-invasive glioblastoma approach to study recurrence events and develop a challenging diagnostic tool

Research Team: Francesca Lessi, Chiara Maria Mazzanti, Sara Franceschi, Mariangela Morelli, Paolo Aretini, Michele Menicagli, Gianmarco Ferri

Glioblastoma (GBMM) is the most aggressive and deadly primary tumor of the central nervous system in adults. The complete surgical resection of this tumor is extremely hard due to the capacity of GBMM to infiltrate the CNS parenchyma. Therefore, inexorable recurrences occur resulting in a dramatic worsening of the prognosis, indeed the average survival of GBM patients is only 16 months. Circulating Tumor Cells (CTCs) are considered to be one of the important causes of tumor recurrence and distant metastases. CTCs present an alternative to invasive biopsies as a means of detecting, characterizing and monitoring disease. GBM was thought to be restricted to the central nervous system for many years. Since brain tumors do not usually metastasize via the bloodstream, it was quite a surprise to find CTCs in the blood of GBM patients. Applying the “seed-and-soil” hypothesis from Paget from 1889, they may have the ability to spread (seed) but cannot find the right target tissue or endothelium (soil), where they can egress, survive, and grow. This is partly due to the tropism that GBM cancer cells present to brain tissues but also the limited overall survival time of the patients may also prevent micro-metastases from growing larger after seeding.
Nevertheless, a growing body of evidence indicates that, like many other cancers, hematogenic dissemination is a reality. Moreover, another significant aspect is the clinical challenge of the GBM diagnosis. Currently, the GBM diagnosis is based on imaging analyses such as Magnetic Resonance Imaging (MRI) with the biopsy as confirmation. Nevertheless, diagnostic errors can occur so the study of CTCs could represent a non-invasive and rapid method to obtain information and improve also the current method of making a diagnosis. The purpose of this project is to isolate and characterize the CTCs in the blood of patients with GBM to study the primary tumor and the intracranial recurrence in the same patient whose CTCs were obtained. This will allow us to define the genetic background of single CTCs compared with the primary tumor and the recurrence to assess whether or not their presence in the peripheral circulation correlates with GBM migration and dissemination and eventually to identify biomarkers involved in tumor cell migration and aggressiveness. Meantime, the analysis of CTCs in some suspicious cases, or after radiotherapy could lead to the identification of an alternative method to image analyses for the diagnosis of GBM.