Figure 5. Models showing the impact of the circadian clock on cisplatin toxicity and tumor shrinkage efficacy for melanoma tumors.

(A) The rhythmical activity of NER in different tissues is an underlying mechanism responsible for chronotherapeutic outcomes in mouse models and human subjects. (B) There is improved efficacy of cisplatin therapy with a more robust immune system as found in Per1/2^−/− mice, probably due to less cisplatin resistance within tumors.