Tumor-targeting Taxane-based Anti-cancer Agents: Synthesis of Next Generation Taxanes and Taxane-based Drug Conjugates Using Linolenic Acid As Tumor-targeting Module

Cancer is the leading cause of death of patients below the age of 85. Traditional chemotherapeutics, such as Taxol ® and Taxotere ® have had a significant impact in the field of chemotherapy because of their unique mechanism of action of inducing apoptosis by stabilizing microtubules during mitotic cell division. However, studies have indicated that these drugs are not active in multi-drug resistant (MDR) cancer cells. MDR arises from the overexpression of ATP-binding cassette proteins which enable the cancer cell to remove cytotoxic agents from the cell via ATP dependent efflux pumps, resulting in the loss of efficacy of the drug. In addition to the problem of MDR, traditional chemotherapeutics have little or no specificity, which leads to systemic toxicity, causing severe and harmful side effects. Therefore, it is important to develop next generation taxoids with increased potency and activity in MDR expressing cancers, as well as to incorporate these cytotoxic agents to tumor-targeting delivery systems to ensure selective cytotoxicity and reduce systemic toxicity. In general, these delivery systems include a tumor-targeting module and a cytotoxic agent.