Abstract
Cancer cells, unlike bacteria and viruses, do not contain molecular targets that are completely foreign to the host. As a result, cytotoxic anticancer therapy has primarily depended on drugs that depend on an increased proliferative rate in the target–cell population, acting primarily on DNA and enzymes involved in DNA replication. However, for patients with advanced disease, clinically approved cytotoxics usually only cause remissions of limited duration and variable degree followed by regrowth and spread of often more aggressive and multidrug–resistant cancer (1). In part this is because cells surviving under hypoxic conditions in the center of tumors are much less susceptible to traditional cancer drugs (2), not only because of their growth–arrested state but also because of limited drug penetration (3) and induced resistance mechanisms (4). When these cells are revived by vascularization, following destruction of the tumor periphery, they often have a higher metastatic potential (5,6). In addition, micrometastases and minimal residual disease (7), often beginning as small populations of cells that evade resection of the primary tumor, often cause clinical relapse (8). Newer approaches to cancer chemotherapy that exploit angiogenesis mechanisms and various signal–transduction pathways have yet to make an impact in the clinic (9–11).
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Dubowchik, G.M. (2002). Principles of Antitumor Targeting of Cytotoxic Drugs. In: Pagé, M. (eds) Tumor Targeting in Cancer Therapy. Cancer Drug Discovery and Development. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-167-1_23
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