Compare and contrast: pediatric cancer versus adult malignancies

Kattner, Patricia; Strobel, Hannah A.; Khoshnevis, N; Grunert, Michael; Bartholomae, Stephan; Pruss, Maximilian; Fitzel, Rahel; Halatsch, Marc‐Eric; Schilberg, Katharina; Siegelin, Markus D.; Peraud, Aurelia; Karpel‐Massler, Georg; Westhoff, Mike‐Andrew; Debatin, Klaus‐Michael

doi:10.1007/s10555-019-09836-y

Cited by 62 publications

(44 citation statements)

References 94 publications

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“…Pediatric soft tissue sarcomas (STSs) are rare malignancies of children and adolescents that accounts for 8% of all pediatric cancers (Kattner et al, 2019). They are highly heterogeneous under a cellular and genomic point of view including subgroups mainly characterized by chromosomal translocations or genomic abnormalities (Gröbner et al, 2018;Knott et al, 2019).…”

Section: Cdk9 Blockade As a Potential Treatment For Pediatric Soft Timentioning

confidence: 99%

CDK9 as a Valuable Target in Cancer: From Natural Compounds Inhibitors to Current Treatment in Pediatric Soft Tissue Sarcomas

et al. 2020

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Cyclin-Dependent Kinases (CDKs) are well-known reliable targets for cancer treatment being often deregulated. Among them, since the transcription-associated CDK9 represents the sentry of cell transcriptional homeostasis, it can be a valuable target for managing cancers in which the transcriptional machinery is dysregulated by tumor-driver oncogenes. Here we give an overview of some natural compounds identified as CDK inhibitors with reported activity also against CDK9, that were taken as a model for the development of highly active synthetic anti-CDK9 agents. After, we summarize the data on CDK9 inhibition in a group of rare pediatric solid tumors such as rhabdomyosarcoma, Ewing's sarcoma, synovial sarcoma and malignant rhabdoid tumors (soft tissue sarcomas), highlighting the more recent results in this field. Finally, we discuss the perspective and challenge of CDK9 modulation in cancer.

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Section: Cdk9 Blockade As a Potential Treatment For Pediatric Soft Timentioning

confidence: 99%

CDK9 as a Valuable Target in Cancer: From Natural Compounds Inhibitors to Current Treatment in Pediatric Soft Tissue Sarcomas

et al. 2020

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“…155 Whereas CAR T-cell therapy has produced some impressive results in this subset of patients, immune-checkpoint inhibitors have been less successful, possibly owing to the lack of neoantigens in paediatric cancers: 155 as mentioned above, differences in the aetiology of adult and paediatric cancers exist-one example being the environmental induction of a high mutational burden in adult cancers that is largely absent from paediatric tumours. 156 Immunotherapy for paediatric cancer patients is not without challenges 157 although generally, fewer patients present with toxicities than those receiving more conventional therapies. However, the risk of severe and potentially fatal side effects remains and tends to be greater in children than in adults.…”

Section: Hypoxia-targeted Treatment Strategy 3: Targeting the Downstrmentioning

confidence: 99%

Hypoxia and its therapeutic possibilities in paediatric cancers

et al. 2020

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In tumours, hypoxia—a condition in which the demand for oxygen is higher than its availability—is well known to be associated with reduced sensitivity to radiotherapy and chemotherapy, and with immunosuppression. The consequences of hypoxia on tumour biology and patient outcomes have therefore led to the investigation of strategies that can alleviate hypoxia in cancer cells, with the aim of sensitising cells to treatments. An alternative therapeutic approach involves the design of prodrugs that are activated by hypoxic cells. Increasing evidence indicates that hypoxia is not just clinically significant in adult cancers but also in paediatric cancers. We evaluate relevant methods to assess the levels and extent of hypoxia in childhood cancers, including novel imaging strategies such as oxygen-enhanced magnetic resonance imaging (MRI). Preclinical and clinical evidence largely supports the use of hypoxia-targeting drugs in children, and we describe the critical need to identify robust predictive biomarkers for the use of such drugs in future paediatric clinical trials. Ultimately, a more personalised approach to treatment that includes targeting hypoxic tumour cells might improve outcomes in subgroups of paediatric cancer patients.

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“…Pediatric cancers affect children and adolescents and, even if considered rare due to the low number of patients, they are the leading cause of death in the young population (as reviewed by Kattner et al, 2019). They are different from the adult ones in term of pathogenic mechanisms and therapeutic approaches including the long-term side effects of therapy that highly impact the life of cancer survivors (Forrest et al, 2018).…”

Section: Crispr/cas9 Technology To Unravel Oncogenic Drivers In Pediatric Soft Tissue Sarcomasmentioning

confidence: 99%

The CRISP(Y) Future of Pediatric Soft Tissue Sarcomas

Pomella

Rota

2020

Front. Chem.

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The RNA-guided clustered regularly interspaced palindromic repeats (CRISPR)/associated nuclease 9 (Cas9)-based genome editing technology has increasingly become a recognized method for translational research. In oncology, the ease and versatility of CRISPR/Cas9 has made it possible to obtain many results in the identification of new target genes and in unravel mechanisms of resistance to therapy. The majority of the studies have been made on adult tumors so far. In this mini review we present an overview on the major aspects of CRISPR/Cas9 technology with a focus on a group of rare pediatric malignancies, soft tissue sarcomas, on which this approach is having promising results.

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Compare and contrast: pediatric cancer versus adult malignancies

Cited by 62 publications

References 94 publications

CDK9 as a Valuable Target in Cancer: From Natural Compounds Inhibitors to Current Treatment in Pediatric Soft Tissue Sarcomas

CDK9 as a Valuable Target in Cancer: From Natural Compounds Inhibitors to Current Treatment in Pediatric Soft Tissue Sarcomas

Hypoxia and its therapeutic possibilities in paediatric cancers

The CRISP(Y) Future of Pediatric Soft Tissue Sarcomas

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