Proteins and peptides as anticancer agents

Cancer is a disease manifested by uncontrolled cell division that presents over 100 distinct clinical pathologies (Kufe et al., 2003). The development of an effective therapy for such a broad spectrum of disease states represents a unique scientific challenge. The conventional cytotoxic therapies such as chemotherapeutic agents and radiation, which cause DNA damage in actively dividing cells, were intended to selectively kill cancer cells while having limited effect on normal cells. Unfortunately, these cytotoxic agents, although effective in managing certain types of cancer, were limited in their utility due to their toxicity to normal dividing cell populations resulting in adverse side effects. Radiation therapy is relatively precise and is used to achieve local control, whereas chemotherapy exerts a systemic effect and is used in a broad array of cancer treatments. However, both therapies have low therapeutic indices and are often highly toxic with a broad spectrum of severe side effects. Another major limitation of successful cancer treatment with both therapies is the development of resistance, which is currently an important clinical problem. Patients who have a tumor relapse usually present with tumors that are more resistant to chemotherapy than the primary tumor. An alternative to cytotoxic therapies is immunotherapy, which aims to manipulate the immune system to create a hostile environment for cancer cells in the body. This is generally achieved through the delivery of biological response modifiers either by genetic modifications of immune cells or by their adoptive transfer, which provide the host with activation signals missing in cancer cells or with activated cells that have antitumor activity. However, all these therapeutic approaches have so far been proved to be inefficient. Moreover, immunotherapies are associated with other common problems, such as adverse toxicity, reversible autoimmunity, tissue penetration, and easy clearance. The associated toxicities and the limited success of traditional cancer treatments in maximizing cure rates has urged the development of new innovative therapeutic strategies based on the emerging knowledge in tumor biology and host-tumor interaction.