Combination chemotherapy seems to be a beneficial choice for some cancer patients particularly when the drugs target different processes of oncogenesis; patients treated with combination therapies sometimes have a better prognosis than those treated with single drug chemotherapy. However, research has shown that this is not always the case, and this approach may only increase toxicity without having a significant effect in augmenting the antitumor actions of the drugs. Doxorubicin (Dox) is one of the most common chemotherapy drugs used to treat many types of cancer, but it also has serious side effects, such as cardiotoxicity, skin necrosis, testicular toxicity, and nephrotoxicity. Many studies have examined the efficacy of melatonin (MLT) as an anticancer agent. In fact, MLT is an anti-cancer agent that has various functions in inhibiting cancer cell proliferation, inducing apoptosis, and suppressing metastasis. Herein, we provide a comprehensive evaluation of the literature concerned with the role of MLT as an adjuvant in Dox-based chemotherapies and discuss how MLT may enhance the antitumor effects of Dox (e.g., by inducing apoptosis and suppressing metastasis) while rescuring other organs from its adverse effects, such as cardio- and nephrotoxicity.
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