IGF2BP1 in 17q-gain cooperates with MYCN to regulate purine biosynthesis and immunotherapy efficacy in neuroblastoma.

IGF2BP1 in 17q-gain cooperates with MYCN to promote neuroblastoma progression through purine biosynthesis and enhances immunotherapy response.

• Why it matters: Understanding how genetic alterations like 17q-gain and MYCN amplification work together can reveal vulnerabilities for targeted treatments in aggressive neuroblastomas.
• What they did: A CRISPR-based screen identified IGF2BP1 as a key MYCN partner that activates PAICS, promoting purine biosynthesis; pharmacological CHK1 inhibition then triggers immune reprogramming and tumor suppression.
• The result: The IGF2BP1/MYCN-PAICS-CHK1 axis offers an actionable target, enabling combined therapies that suppress tumor growth and improve immunotherapy efficacy in neuroblastoma.