Curable and non-curable malignancies: lessons from paediatric cancer

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• Adult cancer treatment progress lags behind molecular understanding, unlike pediatric oncology.
• Apoptosis is crucial for cancer therapy, and resistance to it, often due to p53 activity, leads to treatment failure.

Purpose of the Study:

• To investigate the molecular differences between adult and pediatric cancers.
• To understand why pediatric cancers have a better prognosis and higher cure rates.

Main Methods:

• Comparative analysis of p53 mutation rates in adult versus pediatric tumors.
• Examination of genetic events, oncogene involvement, and chromosomal translocations in both cancer types.
• Assessment of genomic instability, including microsatellite variation, in adult and pediatric malignancies.

Main Results:

• Childhood cancers exhibit significantly lower rates of p53 mutations compared to adult tumors.
• Pediatric tumors often initiate with activated nuclear transcription factors via chromosomal translocations, unlike adult tumors which involve multiple upstream oncogene events.
• Genomic instability is prevalent in adult tumors but largely absent in pediatric tumors.

Conclusions:

• Low p53 mutation rates and distinct genetic pathways contribute to the curability of pediatric cancers.
• The slower progression and higher curability of childhood cancers are linked to their molecular characteristics, including less genomic instability.