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Pineal gland function and melatonin secretion can be impaired due to accidental and developmental conditions, such as pineal tumors, craniopharyngiomas, injuries affecting the sympathetic innervation of the pineal gland, and rare congenital disorders that alter melatonin secretion

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However, accumulating evidence implicates a key role of non-mutational resistance mechanisms underlying drug tolerance, the latter of which is the focus that will be discussed here