DNA Damage Response Inhibitors in Cholangiocarcinoma: Current Progress and Perspectives

Cholangiocarcinoma (CCA) is a poorly treatable type of cancer and its incidence is dramatically increasing. The lack of understanding of the biology of this tumor has slowed down the identification of novel targets and the development of effective treatments. Based on next generation sequencing profiling, alterations in DNA damage response (DDR)-related genes are paving the way for DDR-targeting strategies in CCA. Based on the notion of synthetic lethality, several DDR-inhibitors (DDRi) have been developed with the aim of accumulating enough DNA damage to induce cell death in tumor cells. Observing that DDRi alone could be insufficient for clinical use in CCA patients, the combination of DNA-damaging regimens with targeted approaches has started to be considered, as evidenced by many emerging clinical trials. Hence, novel therapeutic strategies combining DDRi with patient-specific targeted drugs could be the next level for treating cholangiocarcinoma.

Automated summary

Cholangiocarcinoma is a difficult to treat cancer with a rising incidence. Understanding its biology has been a hurdle to identify novel targets and effective treatments. Alterations in DNA damage response-related genes open up possibilities for DDR-targeting strategies. However, using DDR inhibitors alone may not be sufficient for clinical use, leading to consideration of combining them with DNA-damaging regimens and targeted drugs.