A review of predictive, prognostic and diagnostic biomarkers for brain tumours: towards personalised and targeted cancer therapy

Abstract

Background: Brain tumours are relatively rare disease but present a large medical challenge as there is currently no method for early detection of the tumour and are typically not diagnosed until patients have progressed to symptomatic stage which significantly decreases chances of survival and also minimises treatment efficacy. However, if brain cancers can be diagnosed at early stages and also if clinicians have the potential to prospectively identify patients likely to respond to specific treatments, then there is a very high potential to increase patients’ treatment efficacy and survival. In recent years, there have been several investigations to identify biomarkers for brain cancer risk assessment, early detection and diagnosis, the likelihood of identifying which group of patients will benefit from a particular treatment and monitoring patient response to treatment. Materials and methods: This paper reports on a review of 21 current clinical and emerging biomarkers used in risk assessment, screening for early detection and diagnosis, and monitoring the response of treatment of brain cancers. Conclusion: Understanding biomarkers, molecular mechanisms and signalling pathways can potentially lead to personalised and targeted treatment via therapeutic targeting of specific genetic aberrant pathways which play key roles in malignant brain tumour formation. The future holds promising for the use of biomarker analysis as a major factor for personalised and targeted brain cancer treatment, since biomarkers have the potential to measure early disease detection and diagnosis, the risk of disease development and progression, improved patient stratification for various treatment paradigms, provide accurate information of patient response to a specific treatment and inform clinicians about the likely outcome of a brain cancer diagnosis independent of the treatment received.

The role of liquid biopsy in the diagnosis of glioblastoma progression

“…The first attempts to determine tumor ctDNA in the blood of patients with GBM relied on the identification of prognostically significant genetic markers, such as methylation profiles of individual gene promotors, loss of heterozygosity of chromosome 10, IDH1 mutation, and EGFRvIII deletion [59][60][61][62][63][64]. Some studies have shown that tumor ctDNA can be isolated from the GBM patient's blood in 15-88.8 % of cases [54,62,[65][66][67][68][69][70][71].…”

Brain Tumor-Derived Extracellular Vesicles as Carriers of Disease Markers: Molecular Chaperones and MicroRNAs

“…For this reason, repeated attempts have been made over the last few years to identify specific biomarkers that could be detected/measured using noninvasive methods and that would allow early diagnosis and disease monitoring, including controlling the response to treatment [84].…”

Liquid biomarkers for the management of paediatric neuroblastoma: an approach to personalised and targeted cancer therapy

“…37,38 Cancer biomarkers can be either (1) diagnostic (used to identify whether a patient has a specific disease condition), (2) predictive (used to predict response to specific therapeutic interventions) or (3) prognostic (used to inform physicians regarding the risk of clinical outcomes such as cancer recurrence or disease progression). 34,35,[39][40][41][42] According to Osei et al, 34,35 understanding the molecular mechanisms and signalling pathways of biomarkers can potentially lead to personalised and targeted treatment via therapeutic targeting of specific genetic aberrant pathways which play key roles in malignant tumour formation and may provide optimal treatment choices in clinical practice. Biomarkers commonly used for diagnosis, prognostication and therapeutic monitoring can be obtained through either liquid or tissue biopsies.…”

“…Copy number alterations (CNAs) are somatic changes to chromosome structure that result in either a gain or loss of copies in sections of the DNA and have been reported to correlate with the development and progression of cancer. 35,83 According to Combaret et al, 83 high copy numbers are strongly associated with rapid tumour progression and poor outcome, independent of tumour stage or patient age and have become an important factor in treatment stratification. Several studies 41,[93][94][95][96][97][98][99][100][101] have measured MYCN copy number in cfDNA of MYCN-amplified neuroblastoma patients using qPCR to investigate whether qPCR is capable of measuring MYCN gene amplification in serum95 and if MYCN amplification status can identify high-risk neuroblastoma patients who may benefit from early therapeutic intervention or correlates with neuroblastoma prognosis and patient survival.…”

“…Therefore, in recent years, there have been several investigations into the development of various diagnostic, predictive and prognostic cancer biomarkers for patients' stratification and towards personalised and targeted treatment. 34,35 Biomarkers have the potential to measure early disease detection and diagnosis, the risk of disease development and progression, improved patient stratification for various treatment paradigms, provide accurate information of patient response to a specific treatment and inform clinicians about the likely outcome of a cancer diagnosis independent of the treatment received. 6,[34][35][36] In this paper, we report on the literature review of current and emerging clinical biomarkers used in risk assessment, screening for early detection and diagnosis, prognostication and for monitoring the response of treatment of paediatric neuroblastoma cancers.…”