Patients’ Derived Short-Term Glioma Culture: Identification of Aggressive, Drug-Resistant Phenotype

Abstract BackgroundClinical management of glioma is crucial irrespective of tumor grade. Despite newer treatment modalities, the prognosis of glioma is abysmal and, survival statistics are not remarkable. In vitro glioma culture is emerging as a standard model to get insight into phenotypic transformation, drug response, and tumor relapse. In this viewpoint, this study established comprehensive patient-specific short-term cultures comprising low-grade, and high-grade glioma, and evaluated their pertinence in the potential disease management. Methods50 patients with MRI diagnosed glioma were recruited for this study. Primary glioma cultures established from fresh surgical tumor tissues, which were then evaluated for their intrinsic growth kinetics, response to temozolomide, and expression profile of Glial-Mesenchymal Transition (GMT) markers along with an oncogenic marker, cMyc. ResultsShort-term glioma culture was successfully established in 40 clinical samples. Glioma culture, irrespective of tumor grade, displayed two distinct patterns of growth kinetics – one with shorter doubling time (high-proliferating) and another group with longer doubling time (low-proliferating). Significant distinctive features were noticed between these two groups in terms of response to temozolomide, the expression pattern of GMT markers and their association with 1p/19q co-deletion and p53 expression. ConclusionOur findings effectively demonstrated the practicality of the development of short-term glioma culture toward a functional approach for personalized medicine. Our study revealed the presence of a highly proliferative, drug-resistant phenotype irrespective of tumor grade. Hence, short-term culture could be an important prognostic tool for predicting patient clinical responses and cue about imminent tumor relapse.