The development of novel strategies to overcome patient mortality is the primary goal of cancer research. Over the past several decades, the clinical outcome of cancer patients has seen improvements owing to the administration of chemotherapy. Despite its systemic cytotoxic effects, chemotherapy improves patient survival short-term. However, the long-term benefits of chemotherapy remain questionable. Tumor drug resistance, manifesting as cancer relapse and progression, is a significant factor that limits sustained chemotherapy effectiveness. Moreover, recent paradoxical evidence suggests that chemotherapy can adversely affect the disease prognosis. This may be not only due to side-effects of chemotherapy but also due to it directly promoting survival and metastatic dissemination of cancer cells. Here, we review the potential mechanisms by which chemotherapy may increase cancer aggressiveness. We discuss the chemotherapy-induced alterations in vital organs, in cancer cells, and the tumor microenvironment. A better understanding of the chemotherapy effects on the tumor-host interaction will aid in the development of improved strategies to intervene in cancer progression.
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