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. Approximately 300,000 children from infancy to age 14 are diagnosed with cancer worldwide every year (1). Some of the cancer types affecting the pediatric population are also seen in adolescents and young adults (AYA), but it has become increasingly clear that cancers in the latter age group have unique biological characteristics that can affect prognosis and therapy (2).
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. The landscape of genomic alterations in cancers that arise in children, adolescents, and young adults is slowly becoming clearer as a result of dedicated pediatric cancer genome-sequencing projects conducted over the past decade. Of particular note are two recent studies that produced a comprehensive picture of the genomic features that characterize many of the more common pediatric cancers (1, 2). Two major themes have emerged.
Healthy populations translate into productive and stable nations. Universal health care (UHC) is a pragmatic and ethical ideal that, thanks to social and economic progress, seems almost achievable. However, UHC means different things in different contexts. The minimum ideal is that no individual or family should suffer financial hardship because of accessing good-quality medical assistance. Bloom et al. review health priorities around the world and what will be needed in terms of skills, funds, and technology to achieve health care access for all. The September 1978 Alma-Ata Declaration is a landmark event in the history of global health. The declaration raised awareness of "health for all" as a universal human right, whose fulfillment reduces human misery and suffering, advances equality, and safeguards human dignity. It also recognized economic and social development and international security as not only causes, but also consequences, of better health. In addition, it highlighted the power of primary health care and international cooperation to advance the protection and promotion of health in resource-constrained settings. Building on the achievement of Alma-Ata and gaining further traction from the Millenium Development Goals and the Sustainable Development Goals set by the United Nations, universal health care (UHC) has emerged in recent years as a central imperative of the World Health Organization (WHO), the United Nations and most of its member states, and much of civil society. UHC characterizes national health systems in which all individuals can access quality health services without individual or familial financial hardship.
Discussing the use of artificial intelligence (AI) for cancer care in low- and middle-income countries (LMICs) might seem like a paradox, but new technologies have sometimes reached LMICs faster than cancer drugs on the . One example of AI already starting to take hold in cancer care in some LMICs is Watson for Oncology, developed by IBM in partnership with the Memorial Sloan Kettering Cancer Center (MSKCC, New York, NY, USA). Watson for Oncology is a cognitive computing system developed to provide treatment recommendations based on training it receives from published medical literature, publicly available treatment protocols, patient charts, test cases, and guidelines that have been selected by the experts from MSKCC.
I treated an inspiring teenage girl in my clinic the other day. Although Sadie has made a complete recovery from her liver cancer and bears no physical scars from the treatment, anxiety and depression followed her through childhood and adolescence. Last year, I introduced her to our local support group for these adolescent young-adults patients, 13thirty Cancer Connect, and she's blossomed. She hangs out at their local center weekly, has countless new friends, all of whom had or have cancer, and goes on field trips and other programs with them. Her comfort in her own skin and her smile spoke to a young girl transformed. When I commented on this, she said, "I finally found a group of friends who get it."