Perspectives and Challenges in Molecular-Based Diagnostics and Personalized Treatment for Recurrent High-Grade Gliomas Darius Kalasauskas 1 , Mirjam Renovanz 1 , Sven Bikar 2 , Anton Buzdin 3,4,5 , Ather Enam 6 , Sven Kantelhardt 1 , Alf Giese 6 and Ella L Kim 1* 1 Clinic for Neurosurgery, Johannes Gutenberg University Medical Centre, Mainz, Germany 2 Star SEQ GmbH, Mainz, Germany 3 National Research Centre Kurchatov Institute, Centre for Convergence of Nano, Bio, Information and Cognitive Sciences and Technologies, Moscow, Russia 4 First Oncology Research and Advisory Centre, Moscow, Russia 5 Rogachyov Federal Research Centre of Pediatric Hematology, Oncology and Immunology, Moscow, Russia 6 Department of Surgery, Section of Neurosurgery, Aga Khan University Hospital, Karachi, Pakistan * Corresponding author: Ella L Kim, Clinic for Neurosurgery, Laboratory for Experimental Neurooncology, Johannes Gutenberg University Medical Centre, Langenbeckstrasse 1, 55131 Mainz, Germany, Tel: +496131178211; E-mail: ella.kim@unimedizin-mainz.de Received date: March 27, 2017; Accepted date: April 18, 2017; Published date: April 24, 2017 Copyright: © 2017 Kim EL, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Abstract Glioblastoma is the most common and most malignant type of intrinsic brain tumor in adults. The standard of care for glioblastoma consists of surgical debulking followed by combined radiochemotherapy. The clinical efficacy of standard therapies for newly diagnosed glioblastomas is rather modest with the highest survival rate at 5-years being less than 10%. Inevitable recurrence after cytotoxic therapies poses the major challenge in the clinical management of high grade gliomas. For recurrent glioblastomas, there is no standard therapy with lack of level one evidence for treatment efficacy. Recent evidence indicates that post-therapy recurrence in gliomas is a consequence of a plethora of molecular and cellular factors including intratumoural heterogeneity, functional hierarchy of distinct types of glioma cells, dynamic changes in the molecular landscapes and cellular composition of the tumour during therapy and the impact of particular treatment modalities. There is an emerging consensus that molecular distinctions within and between individual tumours is an important factor determining clinical outcomes. Consequently, integrated approaches based on the combination of molecular profiling with traditional methods such as immunohistochemical phenotyping, karyotyping and/or non-quantitative methylation-specific PCR have emerged as a promising venue towards increasing the predictive value of diagnostics for malignant brain tumors. The high level of inter-and intra-tumoural molecular diversity in gliomas underscores the need of integrating high throughput molecular profiling and pharmacogenomics into a diagnostic paradigm for gliomas and raises the possibility that molecular-instructed personalized treatments may provide clinical benefit to patients with glioblastoma, particularly in the setting of post-treatment recurrence. Here we discuss potential prospects and challenges of patient-tailored diagnostics and personalized treatment strategies for recurrent glioblastomas. Keywords: Glioblastoma; Glioblastoma recurrence; Glioma stem cells; Intratumoural heterogeneity; Molecular diagnostics; High throughput profling; Personalised medicine Personalized Approach to Cancer Treatment Personalized cancer therapy is the most promising also most challenging area of research in modern oncology. Refecting this fact, PubMed search by terms “personalized cancer therapy”, “precision cancer treatment” or “individualized cancer therapy” yields 4619, 4982 and 3821 entries as of March 2017. Te underlying concept is that molecular distinctions between individual tumours/tumour subtypes within the same cancer can provide important instructions for delineating most efective treatment schemes particularly for cancers poorly responding to conventional treatments. Consequently, developing patient-tailored individualised therapy (IT) has become recognized as a promising venue improving the accuracy of diagnosis and stratifcation of treatment schemes for patients with treatment- refractory cancers [1-3]. A direct relationship between the level of genetic complexity and poor efcacy of therapeutic strategies based on the “one-treatment-for-all” principle can be seen in glioblastoma, a genetically complex cancer characterized by a high degree of molecular and cellular heterogeneity. Te promise of high-throughput molecular- based diagnostics as a strategy for more accurate patient stratifcation and prognostic staging has been recognized as a matter of urgent priority for improving the efcacy of glioblastoma therapy [4,5]. In this article, we discuss the current state, perspectives and specifc challenges in molecular characterization and development of personalized approaches for treatment-refractory glioblastoma. Glioblastoma: General Facts Glioblastoma is the most common, most aggressive and inevitably lethal brain tumor in adults [6]. A dismal prognosis in conjunction with limited treatment options place glioblastomas among most challenging human cancers today. Age and gender are the most signifcant risk factors. Glioblastoma is most frequently diagnosed at a later age (median age at diagnosis 64 years old), occur at slightly higher rates in men than women and have the highest rate of incidence in Caucasians [7-9]. Although a higher risk of developing gliobalstoma has been associated with radiation exposure and germ line mutations causing neurofbromatosis (NF1 and NF2), Li Fraumeni syndrome (TP53), melanoma-astrocytoma syndrome (CDKN2A), tuberous sclerosis (TSC1/TSC2), Turcot syndrome (mismatch repair genes) and Kalasauskas et al., J Carcinog Mutagen 2017, 8:2 DOI: 10.4172/2157-2518.1000290 Review Open Access J Carcinog Mutagen, an open access journal ISSN:2157-2518 Volume 8 • Issue 2 • 1000290 e s M s Journal of Journal of Car Carcinogenesis & Mutagenesis cinogenesis & Mutagenesis J o u r n a l o f C a r c i n o g e n s i & u t a g e n e s i ISSN: 2157-2518 ISSN: 2157-2518