A first-generation pediatric cancer dependency map.

Area of Science:

• Genomics
• Cancer Biology
• Drug Discovery

Background:

• High mutational-burden adult cancers have yielded therapeutic targets via CRISPR screens.
• Pediatric cancers have fewer mutations and challenging drug targets, questioning the utility of functional genomics.

Purpose of the Study:

• To investigate if functional genomic approaches can identify therapeutic targets in pediatric cancers.
• To create a pediatric cancer dependency map using genome-scale CRISPR-Cas9 screening.

Main Methods:

• Genome-scale CRISPR-Cas9 loss-of-function screening was performed on 82 pediatric cancer cell lines.
• The study covered 13 distinct pediatric solid and brain tumor types.
• Identified genes essential for cancer cell survival.

Main Results:

• Pediatric cancer cell lines exhibit a complexity of genetic dependencies comparable to adult cancer models.
• Despite fewer mutations, pediatric cancers show a rich landscape of vulnerabilities.
• Identified dependencies in pediatric cancers are often distinct from those in adult cancers.

Conclusions:

• Functional genomic screening is a viable approach for identifying therapeutic targets in pediatric cancers.
• The distinct genetic vulnerabilities in pediatric cancers necessitate novel therapeutic strategies.
• Repurposing drugs approved for adult cancers may be insufficient for treating childhood cancers.