Childhood Cancer: Research Progress and Future Prospects

February 15th is International Childhood Cancer Day, reminding us that childhood cancer deserves more attention since more than 250,000 children are diagnosed with cancer and about 90,000 children die from cancer every year.

In recent years, the incidence of childhood cancer has been increasing, but children suffering from cancer have not received enough attention from all walks of life. How to make breakthroughs in the field of childhood cancer treatment and find more accurate and effective treatments is a problem that scientists worldwide have been exploring. Recent research on childhood cancer has made some new progress.

Precision medicine of childhood cancer: JAMA Network Open published a research result of the CHU Sainte-Justine TRICEPS team that genomic profiling will help clinical treatment of childhood cancer. Until April 2019, the team had enrolled 84 patients. In 87% of patients, the study identified genomic anomalies that allowed for better patient management. The therapeutic alternatives are personalized because the proposed actions will be different for each patient. The discoveries can lead to a "targeted" therapy because it specifically seeks to block (or bypass) the action of genes that cause cancer progression.

Gene technology for Ewing sarcoma: Ewing sarcoma is a childhood cancer driven by EWS-ETS transcription factor fusion oncoproteins. The majority of tumors express wild-type TP53, and thus, therapies targeting the p53 pathway would benefit most patients. To discover targets specific for TP53 wild-type Ewing sarcoma, scientists used a genome-scale CRISPR-Cas9 screening approach and identified and validated MDM2, MDM4, USP7, and PPM1D as druggable dependencies.

New target for treating childhood cancer: SWI/SNF is a multi-component protein complex that plays an important role in chromatin remodeling. It is also likely an important tumor suppressor, as indicated by the fact that approximately 20% of human cancers carry a mutation in one or more SWI/SNF protein components. This SWI/SNF component protein is mutated in a number of cancers, including malignant rhabdoid tumor (MRT), a highly aggressive, nearly uniformly fatal childhood cancer. William Tansey and his laboratory found that cancers bearing an SNF5 mutation may be susceptible to therapy by MYC inhibition, providing yet another reason why the discovery of clinically viable MYC inhibitors is of utmost importance.

The purpose of modern childhood cancer treatment is not only for the survival rate and the extension of survival time, but also to improve the quality of life. The principle of treatment of pediatric tumors has been raised to the integration of eradication of tumor, functional maintenance and mental health.

For the first two principles, childhood cancer patients are very different from adults, for they are at the stage of growth, thus the treatment plan must take the impact of treatment on the normal development of children into consideration. For example, the widespread use of radiation therapy in adults has been severely limited in childhood cancer treatment due to the risk of skeletal deformities, gonad damage, and intellectual effects in children. In the future, there will be anti-tumor drugs and treatment being more safe, effective, and less toxic, such as biological treatment, gene therapy, differentiation induction therapy to replace traditional chemotherapy and radiotherapy.

For mental health, on the basis of further improvement of tumor eradication and long-term survival, the mental health of children with tumors will be increasingly valued. Psychological problems, including children's self-experience, psychological effects, concerns about relapses and difficulties in participating in society, should be brought to the attention. Parents should be noticed that organ function and appearance reconstruction are also necessary for those who have suffered growth stagnation, and whose appearance is abnormal due to surgery and radiation therapy.

In short, the childhood cancer treatment is being improved, and under the premise of continuous increase of survival rate, children's long-term psychological and physical health, as well as functional maintenance must be considered when formulating treatment plans.

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