Replication stress resistance as therapeutic target in NB

​Genomic instability is an enabling hallmark of cancer. However, malignant cells should be able to adapt to accumulating DNA damage, since this may cause stalling or even collapse of the replication forks, a situation known as replicative stress, which has a negative impact on proliferation. As cancer cells strongly depend on such adaptations, they can serve as targetable vulnerabilities.
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Interestingly, embryonal tumors, such as neuroblastoma, appear to have retained the replicative stress resistant phenotype of embryonic stem cells, which protects them from DNA damage induced premature aging. Moreover, recent studies point out that pediatric cancer types, amongst which also NB, have vulnerabilities that can be very distinct from those in adult cancers and should receive particular attention.