DNA Damage Response Inhibitors in Cholangiocarcinoma: Current Progress and Perspectives.
Öykü Gönül GeyikGiulia AnichiniEngin UlukayaFabio MarraChiara RaggiPublished in: Cells (2022)
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.
Keyphrases
- dna damage response
- dna repair
- dna damage
- cell death
- cancer therapy
- clinical trial
- end stage renal disease
- circulating tumor
- ejection fraction
- newly diagnosed
- chronic kidney disease
- papillary thyroid
- oxidative stress
- peritoneal dialysis
- risk factors
- randomized controlled trial
- single molecule
- drug delivery
- squamous cell carcinoma
- gene expression
- squamous cell
- patient reported outcomes