Many classes of drugs have been used with radiotherapy. Anti-metabolites such as 5-FU were among the earliest radiosensitizers (Bagshaw 1961; Buchholz et al. 1995). A newer nucleoside analog, gemcitabine, is a potent sensitizer (Scalliet et al. 1998). Platinum-based drugs have been widely used, including cisplatin (Dewit 1987), carboplatin (O'Hara et al. 1986; Begg et al. 1987), and more recently oxalipla-tin (Freyer et al. 2001). The taxanes paclitaxel and docetaxel inhibit the mitotic spindle by promoting microtubule assembly and inhibiting disaggrega-tion (Rowinsky 1997); this leads to cellular arrest in the G2M phase of the cell cycle, a point of increased radiosensitivity (Hall 1994). The camptothecins, such as irinotecan and topotecan, target DNA topoi-somerase I (Hsiang et al. 1985; Hsiang and Liu 1988). Other agents have included mitomycin C91, which targets hypoxic cells which are relatively radioresistant (Bristow and Hill 1998).
Newer strategies of combining systemic therapy with irradiation involve exploiting targets in the signal transduction pathways of cells, such as EGFR, or angiogenic factors supporting the growth of tumor vasculature (Mason et al. 2001). EGFR is involved in tumor growth and response to cytotoxic agents, including ionizing radiation, and expression of the receptor in a cancer is often associated with an aggressive neoplasm that is resistant to chemotherapy (Mendelsohn and Fan 1997; SchmidtUllrich et al. 2000). The formation of blood vessels necessary for tumor growth is dependent on angiogenic factors such as VEGF, and inhibitors have been shown to improve the efficacy of irradiation (Teicher et al. 1995; Mauceri et al. 1998).
There are numerous other new, targeted agents that hold the promise of improving outcomes from therapy not discussed above. They will aim to specifically block the action of numerous specific targets, including: cyclin-dependent kinase, mito-gen-activated protein kinase, farnesyl transferases, mitogen-activated protein kinase, PI 3'-kinase, matrix metalloproteinases, and Bcl-2 (Raben et al. 2004).
Was this article helpful?