Catálogo de publicaciones - revistas

<jats:p>Cancer treatment takes a toll on small bodies. As more children survive the disease, there's a push to better their health in the years ahead.</jats:p>

<jats:p>The past decade has witnessed a major increase in our understanding of the genetic underpinnings of childhood cancer. Genomic sequencing studies have highlighted key differences between pediatric and adult cancers. Whereas many adult cancers are characterized by a high number of somatic mutations, pediatric cancers typically have few somatic mutations but a higher prevalence of germline alterations in cancer predisposition genes. Also noteworthy is the remarkable heterogeneity in the types of genetic alterations that likely drive the growth of pediatric cancers, including copy number alterations, gene fusions, enhancer hijacking events, and chromoplexy. Because most studies have genetically profiled pediatric cancers only at diagnosis, the mechanisms underlying tumor progression, therapy resistance, and metastasis remain poorly understood. We discuss evidence that points to a need for more integrative approaches aimed at identifying driver events in pediatric cancers at both diagnosis and relapse. We also provide an overview of key aspects of germline predisposition for cancer in this age group.</jats:p>

<jats:p>Cancer treatment decisions are increasingly based on the genomic profile of the patient’s tumor, a strategy called “precision oncology.” Over the past few years, a growing number of clinical trials and case reports have provided evidence that precision oncology is an effective approach for at least some children with cancer. Here, we review key factors influencing pediatric drug development in the era of precision oncology. We describe an emerging regulatory framework that is accelerating the pace of clinical trials in children as well as design challenges that are specific to trials that involve young cancer patients. Last, we discuss new drug development approaches for pediatric cancers whose growth relies on proteins that are difficult to target therapeutically, such as transcription factors.</jats:p>

<jats:p>Each year ~429,000 children and adolescents aged 0 to 19 years are expected to develop cancer. Five-year survival rates exceed 80% for the 45,000 children with cancer in high-income countries (HICs) but are less than 30% for the 384,000 children in lower-middle-income countries (LMICs). Improved survival rates in HICs have been achieved through multidisciplinary care and research, with treatment regimens using mostly generic medicines and optimized risk stratification. Children’s outcomes in LMICs can be improved through global collaborative partnerships that help local leaders adapt effective treatments to local resources and clinical needs, as well as address common problems such as delayed diagnosis and treatment abandonment. Together, these approaches may bring within reach the global survival target recently set by the World Health Organization: 60% survival for all children with cancer by 2030.</jats:p>