Research Topic

Novel Molecular Targets and Therapies for Pediatric Solid Tumors

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Although the outcome of childhood solid cancers has improved over the last few decades, the main line of therapy still relies on conventional treatments, including DNA-damaging agents, and radiotherapy, neither of which address the underlying disease mechanisms, and in turn have significant side-effects and ...

Although the outcome of childhood solid cancers has improved over the last few decades, the main line of therapy still relies on conventional treatments, including DNA-damaging agents, and radiotherapy, neither of which address the underlying disease mechanisms, and in turn have significant side-effects and toxicities, sometimes lasting for extended periods of time. Furthermore, some pediatric cancers, like high-risk medulloblastoma and rhabdomyosarcoma, remain difficult to treat with traditional methods and frequently lead to relapse and loss of life. Therefore, it is imperative to explore proteins and signaling pathways that act as drivers of disease, thereby identifying potential drug targets and pharmaceutical agents that could provide novel and selective treatment options.

The advent of genomic sequencing has enabled the discovery of potential driver mutations in many childhood and adult cancers, and mutations that arise in relapsing disease, thus paving the way for personalized and targeted treatment. There has been an exponential growth in scientific publications about molecular disease mechanisms and new targets for childhood cancers, leading to preclinical testing of promising compounds. Unfortunately, this revolutionary change has yet to reach the clinic, and pediatric oncologists still struggle with the paucity of new agents and treatment options.

The introduction of new drugs into clinical practice in pediatric oncology faces many challenges, including the difficulty of recruitment into clinical trials due to low patient numbers, and the unknown safety profiles of drugs in children. Nevertheless, repurposing of compounds already approved for treatment in adults can significantly speed up the drug development process. Several drugs have reached clinical trials for childhood cancers, such as the ALK and ROS1 inhibitor Crizotinib, already approved for use in lung cancer in adults, being currently trialed for neuroblastoma and rhabdomyosarcoma. Similarly, the MEK/ERK inhibitor Trametinib, which is in use for melanoma, has entered clinical trials for neuroblastoma. Immunotherapies have come to the forefront of emerging treatment options. Dinutuximab, targeting GD2, has become a front-line treatment in neuroblastoma, while other modalities of immunotherapy, including CAR-T cells, are also in the development pipeline.

Some oncogenes, like MYCN, have a strong association with poor prognosis and a well-established causal link to pathogenesis, yet there has been limited success in directly targeting this transcription factor for therapeutic intervention. Although inhibition of transcription factors remains challenging, characterizing the oncogenic network around this oncoprotein enabled the discovery of a few promising “druggable” candidates, including SIRT2, Aurora kinase A, and PRMT5, which can affect the stability of the MYCN protein. The Aurora-kinase inhibitor, Alisertib is now in clinical trials for neuroblastoma and rhabdomyosarcoma.

Despite these recent advances, personalized treatment options are scarce in childhood cancers, especially in rare diseases like Wilms’ tumor. This research topic focuses on the emergence of molecular targets and small molecule inhibitors that may lead to the development of novel targeted therapies for embryonic solid tumors, including neuroblastoma, rhabdomyosarcoma, medulloblastoma and Wilms’ tumor. We welcome original scientific publications and reviews characterizing novel molecular targets, mechanisms of tumorigenesis, and small molecule inhibitors for these and other pediatric solid tumors.


Keywords: Neuroblastoma, rhabdomyosarcoma, Wilms’ tumour, medulloblastoma, Targeted therapy


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