Improved patient-tailored, more potent, and durable treatment of childhood cancer is an urgent medical need. Children with cancer are often still treated by a "one-fits-all" approach, given the limited available entry points for targeted therapy in this field. Just as children are not adults, childhood cancer differs in many aspects from adult cancers, the latter typically resulting from lifelong accumulation of genetic defects. In contrast, childhood cancers rather display a very low mutational burden and unique biology of co-opted developmental pathways. Therefore, building a next-generation precision oncology platform for childhood cancer will require a dedicated multidisciplinary and integrative scientific approach in which state-of-the-art technologies serve as a driving force to untangle the (epi)genetically rewired networks and fuel contemporary pre-clinical target evaluation.
Current advances in the molecular dissection of pediatric cancers using multiple layers of information up to the single-cell level (so-called ‘omics’) are yielding fundamental insights into novel putative targets and strategies for precision oncology approaches. Especially drug combinations, which can enhance efficacy and reduce drug resistance compared to single targeted compounds, are promising avenues for new successful clinical trials. Furthermore, bringing targeted therapy to the next level will not only require rationally designed small molecule combination therapeutic regimens but will also demand the implementation of innovative strategies such as target sequestration and degradation, the latter through PROTAC or molecular glue initiatives. The targeted protein degradation using small molecules recently became attractive as a pharmacological knockdown strategy. Compared to target blockers/inhibitors, post-translational protein degradation resembles more closely phenocopies genetic approaches to target validation and can lead to a more sustained cellular effect. PROTACs act catalytically as any one molecule may perform multiple rounds of target ubiquitination and degradation. This results in potential therapeutic benefits over conventional small molecule drugs, including improved potency, specificity, catalytic activity, and prolonged pharmacodynamics. PROTACs have been proven capable of targeting intracellular proteins that historically have been undruggable or ineffectively drugged with conventional small molecules.
The overall aim of this Research Topic is to build a better understanding of the phenotypic and molecular consequences of novel targets, targeted drug combinations and/or targeted protein degradation in the field of pediatric oncology.
We would welcome original research papers and (mini)reviews including but not limited to the following topics in pediatric cancer:
1. Novel targets for precision medicine
2. Promising drug combinations
3. Targeted protein degradation
Please note: manuscripts consisting solely of bioinformatics, computational analysis, or predictions of public databases which are not accompanied by validation (independent cohort or biological validation in vitro or in vivo) will not be accepted in any of the sections of Frontiers in Oncology.
Improved patient-tailored, more potent, and durable treatment of childhood cancer is an urgent medical need. Children with cancer are often still treated by a "one-fits-all" approach, given the limited available entry points for targeted therapy in this field. Just as children are not adults, childhood cancer differs in many aspects from adult cancers, the latter typically resulting from lifelong accumulation of genetic defects. In contrast, childhood cancers rather display a very low mutational burden and unique biology of co-opted developmental pathways. Therefore, building a next-generation precision oncology platform for childhood cancer will require a dedicated multidisciplinary and integrative scientific approach in which state-of-the-art technologies serve as a driving force to untangle the (epi)genetically rewired networks and fuel contemporary pre-clinical target evaluation.
Current advances in the molecular dissection of pediatric cancers using multiple layers of information up to the single-cell level (so-called ‘omics’) are yielding fundamental insights into novel putative targets and strategies for precision oncology approaches. Especially drug combinations, which can enhance efficacy and reduce drug resistance compared to single targeted compounds, are promising avenues for new successful clinical trials. Furthermore, bringing targeted therapy to the next level will not only require rationally designed small molecule combination therapeutic regimens but will also demand the implementation of innovative strategies such as target sequestration and degradation, the latter through PROTAC or molecular glue initiatives. The targeted protein degradation using small molecules recently became attractive as a pharmacological knockdown strategy. Compared to target blockers/inhibitors, post-translational protein degradation resembles more closely phenocopies genetic approaches to target validation and can lead to a more sustained cellular effect. PROTACs act catalytically as any one molecule may perform multiple rounds of target ubiquitination and degradation. This results in potential therapeutic benefits over conventional small molecule drugs, including improved potency, specificity, catalytic activity, and prolonged pharmacodynamics. PROTACs have been proven capable of targeting intracellular proteins that historically have been undruggable or ineffectively drugged with conventional small molecules.
The overall aim of this Research Topic is to build a better understanding of the phenotypic and molecular consequences of novel targets, targeted drug combinations and/or targeted protein degradation in the field of pediatric oncology.
We would welcome original research papers and (mini)reviews including but not limited to the following topics in pediatric cancer:
1. Novel targets for precision medicine
2. Promising drug combinations
3. Targeted protein degradation
Please note: manuscripts consisting solely of bioinformatics, computational analysis, or predictions of public databases which are not accompanied by validation (independent cohort or biological validation in vitro or in vivo) will not be accepted in any of the sections of Frontiers in Oncology.
