Intrinsic mechanisms that protect the genome against replication stress and damage
Certain cancers are characterized by high levels of DNA replication stress due to increased signaling from oncogenic cells. This phenomenon renders such cancers significantly more susceptible than normal cells to therapies that constrain nucleotide biosynthesis. However, these therapies are often ineffective because of three mechanisms:
The ability of cancer cells to switch their nucleotide production to alternate biosynthetic pathways
Biological controls that rapidly adjust consumption to compensate for insufficient production
Identification of the key checkpoints that control these three resistance mechanisms has enabled the development of pharmacological agents that specifically intervene within these pathways.