RESUMEN
Whole-genome sequencing (WGS) and whole-exome sequencing (WES) are crucial within the context of breast cancer (BC) research. They play a role in the detection of predisposed genes, risk stratification, and identification of rare single nucleotide polymorphisms (SNPs). These technologies aid in the discovery of associations between various syndromes and BC, understanding the tumour microenvironment (TME), and even identifying unknown mutations that could be useful in future for personalised treatments. Genetic analysis can find the associated risk of BC and can be used in early screening, diagnosis, specific treatment plans, and prevention in patients who are at high risk of tumour formation. This article focuses on the application of WES and WGS, and how uncovering novel candidate genes associated with BC can aid in treating and preventing BC.
RESUMEN
Brain tumours are the leading cause of paediatric cancer-associated death worldwide. High-grade glioma (HGG) represents a main cause of paediatric brain tumours and is associated with poor prognosis despite surgical and chemoradiotherapeutic advances. The molecular genetics of paediatric HGG (pHGG) are distinct from those in adults, and therefore, adult clinical trial data cannot be extrapolated to children. Compared to adult HGG, pHGG is characterised by more frequent mutations in PDGFRA, TP53 and recurrent K27M and G34R/V mutations on histone H3. Ongoing trials are investigating novel targeted therapies in pHGG. Promising results have been achieved with BRAF/MEK and PI3K/mTOR inhibitors. Combination of PI3K/mTOR, EGFR, CDK4/6, and HDAC inhibitors are potentially viable options. Inhibitors targeting the UPS proteosome, ADAM10/17, IDO, and XPO1 are more novel and are being investigated in early-phase trials. Despite preclinical and clinical trials holding promise for the discovery of effective pHGG treatments, several issues persist. Inadequate blood-brain barrier penetration, unfavourable pharmacokinetics, dose-limiting toxicities, long-term adverse effects in the developing child, and short-lived duration of response due to relapse and resistance highlight the need for further improvement. Future pHGG management will largely depend on selecting combination therapies which work synergistically based on a sound knowledge of the underlying molecular target pathways. A systematic investigation of multimodal therapy with chemoradiotherapy, surgery, target agents and immunotherapy is paramount. This review provides a comprehensive overview of pHGG focusing on molecular genetics and novel targeted therapies. The diagnostics, genetic discrepancies with adults and their clinical implications, as well as conventional treatment approaches are discussed.
