The management of many cancers has changed as more biological agents have become available. For some, such as renal cell cancer and melanoma, in which chemotherapy has only limited effectiveness, targeted agents are now the mainstay of treatment. For others, where developments in chemotherapy have improved survival rates but increased toxicity, biological agents provide additional benefit with manageable toxicity, when alone or in combination with chemotherapy.
The licensed indications for new drugs are changing rapidly. A useful resource for up-to-date information can be found in the electronic Medicines Compendium (www.medicines.org.uk/emc, accessed January 2015). However, although they are licensed, several of these biological agents are not available for routine use in the UK.
This chapter is an overview of the biological agents in current use in the UK, and covers their mode of action and side effects. Their specific clinical indications will be described in the individual tumour chapters. This chapter will concentrate on five areas:
• protein kinase inhibitors and small molecule drugs,
• monoclonal antibodies,
• haemopoietic colony-stimulating factors, and
Protein kinase inhibitors
Protein kinase inhibitors are predominantly oral agents, often with different, non-overlapping toxicities from chemotherapy, which allow them to be safely combined with chemotherapy and radiotherapy or to be given alone.
The targets for these drugs are the tyrosine and serine/threonine kinases. These enzymes transfer phosphate groups from ATP to specific amino acid residues on a protein through phosphorylation. The protein kinase inhibitors act by binding to the intracellular kinase region, directly competing with ATP, and thus preventing autophosphorylation. This in turn blocks the intracellular signalling cascades involved with the promotion of tumour growth, invasion, angiogenesis and resistance to apoptosis. They can be subdivided into receptor and non-receptor kinases.
The receptor kinase is an integral part of the receptor molecule spanning the cell membrane. Ligand binding to the receptor activates signalling pathways, and affects the activity of transcription factors and DNA synthesis. These include the epidermal growth factor receptor (EGFR), and the vascular endothelial growth factor receptor (VEGFR).