Cell death-based treatment of childhood cancer

Abstract

Any therapy that aims at eradicating a cancerous growth will have at its core a cell death-inducing component. Here we argue that paediatric oncology presents with its unique set of considerations and problems, which—while taking the lead from oncological research experiences obtained from the adult population—need to be clinically evaluated independently. This is particularly true when considering long-term side effects. Precision medicine offers a promising new approach in therapy, but given as a monotherapy and in a limited combination, as found in an apoptosis inducer/sensitiser combination, it will most likely lead to mutation escape of the target cell population and the emergence of resistance. However, using the increasing amount of the molecular data as the basis for a complex combination therapy combining several key components such as cell death-inducing agents, kinase inhibitors and BH3 mimetics, holds great promise.

Combinatorial targeting of MTHFD2 and PAICS in purine synthesis as a novel therapeutic strategy

“…Treatment that combines two or more specific therapeutic targets might reduce the dosage and side-effect for aggressive therapy in children 57 . Our dual knockdown and co-treatment assays that target MTHFD2 and PAICS had synergistic effects on MNA neuroblastoma which might diminish the aggressiveness and tumor progression ability.…”

Precision medicine in pediatric oncology

“…Normally, cells receive external signals that are transmitted into the cell by receptors, for instance tyrosine kinase receptors transmitting signals through phosphorylating tyrosine residues of proteins. Deregulated activation of tyrosine kinases is characteristic of most cancers [ 42 ] (Fig. 2 ).…”

“…Cancer cells are defined by overactive signaling cascades, often mediated by tyrosine (tyr) kinases. Common therapeutic strategies are either blocking of the tyr kinase receptor by inhibiting antibody/pharmacological inhibitor (which does not work for ligand-independent signals and has reduced potency if the target is overexpressed), or utilizing pharmacological inhibitors that block kinase activity (dependent/independent of mutational status) [ 42 ] …”

Aktuelle Behandlungskonzepte für Hirntumoren im Kindes- und Jugendalter

“…bessere Optionen für die Therapie zu haben. Allerdings eröffnen sich genau hier neue Schwierigkeiten, denn schon der deutsche Arzt Abraham Jacobi, der als einer der Gründer der modernen Kinderheilkunde gilt, formulierte die Prämisse: Kinder sind nicht kleine Erwachsene [19].…”