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Unit 3   Applying concepts from the nursing process

predictor of resistance to standard chemotherapy, and a poor patient prognosis (Oishi, 2008). Recent scientific advances have enabled the development of numerous new targeted therapy drugs that bind to a specific protein receptor or block a specific signal transduction pathway expressed by a tumour but not by a normal cell, enabling a very targeted, specific cell kill. Monoclonal antibodies bind to the extracellular protein receptors and are larger molecules that are administered by IV. Tyrosine kinase inhibitors are smaller molecules that target the intracellular signalling pathways and are given orally. The efficacy of these new targeted agents depends on consistent and reliable delivery, and because they involve the patient’s natural immune system, they can precipitate very significant adverse events specific to each agent. It is important for nurses to be familiar with the administration issues related to patient education about self-administered oral agents and patient safety related to adverse events (Khoukaz, 2006). Vascular endothelial growth factors.  Angiogenesis requires growth factors, cytokines, enzymes and proteins, all generated by the tumour to stimulate the formation of new capillaries to deliver oxygen and other nutrients to the hypoxic tumour. The major pathway for angiogenesis is activation of the VEGF family of proteins (Franson & Lapka, 2005; Viele, 2005). VEGF is essential for the growth and proliferation of malignant cells and, when activated, stimulates growth of new blood ves- sels. These new blood vessels differ greatly from normal vessels with less well-organised structure, increased permeability allowing migration of tumour cells, and increased interstitial pressure preventing chemotherapy from reaching the tumour. VEGF is overexpressed in many solid tumours and is associated with advanced tumour stage and poor prognosis (Viele, 2005). In colorectal cancer, increased VEGF expression has been cor- related with increased vascularity, invasiveness, metastasis and poor prognosis (Franson & Lapka, 2005). Bevacizumab (Avastin) is a MoAb directed towards VEGF to prevent the activation of endothelial cells and inhibit growth of new blood vessels. Research is ongoing to evaluate its effectiveness with other solid tumours. Side effects of beva- cizumab include delays in wound healing, haemorrhage, hyper- tension, thromboembolism and proteinuria. Newer agents such as sorafenib (Nexavar) and sunitinib (Sutent) have shown multitargeted activity against VEGF cell receptors and tyrosine kinase pathways and have been approved for metastatic renal cell carcinoma. Cytokines Cytokines , substances produced by cells of the immune system to enhance the production and functioning of components of the immune system, are also the focus of cancer treatment research. Cytokines are grouped into families, such as inter- ferons, interleukins, colony-stimulating factors and tumour necrosis factors (TNFs). Refer to Chapter 45 for more detailed discussion of the immune system. Interferon.  Interferons (IFNs) are examples of cytokines with both antiviral and antitumour properties. When stimulated, all nucleated cells are capable of producing these glycoproteins, which are classified according to their biological and chemical properties: IFN α is produced by leucocytes, IFN β is produced by fibroblasts, and IFN- γ is produced by lymphocytes. Although the exact antitumour effects of IFNs have not been thoroughly established, it is thought that they either

MoAbs are being used as aids in diagnostic evaluation. By attaching a radioactive substance to the MoAb, doctors can detect both primary and metastatic tumours through radiologi- cal techniques. This process is referred to as radioimmunodetec- tion. OncoScint is a Therapeutic Goods Association (TGA), Medicine and Medical Devices Safety Authority (MEDSAFE), Federal Drug Administration (FDA) and Pharmaceutical Management Agency (PHARMAC)-approved MoAb that is used to assist in diagnosing ovarian and colorectal cancers. The use of MoAbs in detecting breast, gastric and prostate cancers and lymphoma is under investigation. MoAbs are also used in purging residual tumour cells from the bone marrow or periph- eral blood of patients who are undergoing BMT for peripheral stem cell rescue after high-dose cytotoxic therapy. Several MoAbs have been approved for treatment in cancer. Rituximab (Rituxan) is used for the treatment of relapsed or refractory non-Hodgkin’s lymphoma (Morschhauser et al., 2009). Trastuzumab (Herceptin) is approved as a single agent or given in addition to chemotherapy for the treatment of some types of metastatic breast cancer (Buzdar, 2009). Alemtuzumab (Campath) is used in the treatment of some forms of leukaemia. Gemtuzumab ozogamicin (Mylotarg) is a combination of a MoAb and the antitumour antibiotic cali- cheami cin, which is used for the treatment of a specific type of acute myeloid leukaemia (Taksin et al., 2007). Gemtuzumab ozogamicin is an example of immunoconjugate therapy or a ‘magic bullet’ that transports cancer-killing substances to the cancer cells. Ibritumomab-tiuxetan (Zevalin) is another form of immunoconjugate therapy that combines a monoclonal antibody and a radioactive source for the treatment of specific types of non-Hodgkin’s lymphoma. The monoclonal antibody delivers the radioactive source to the malignant cells, causing the cells to be destroyed by both radioactivity and normal immune responses. Researchers are continuing to explore the development and use of other MoAbs either alone or in com- bination with other substances such as radioactive materials, chemotherapeutic agents, toxins, hormones or other BRMs (Kay, 2006; Wilkes & Barton-Burke, 2007). Epidermal growth factor receptors and tyrosine kinase pathways.  Normal cell growth is regulated by well- defined communication pathways between the environment surrounding the cell and the internal cell environment, the nucleus, and the intracellular cytoplasm. The cell membrane contains important protein receptors that respond to signals transmitted from the external environment and transmit that signal to the internal cell environment using enzymatic pathways called signal transduction pathways. Advances in understanding the genetic nature of cancers have resulted in these protein receptors and the cellular communication path- ways being used as targets for new cancer treatment agents. Much like a lock and key mechanism, new drugs are being developed that will target these specific receptors and path- ways and prevent the continued growth of the cancer cells. The family of epidermal growth factor receptors (EGFR) has been proven to be a critical communication pathway. EGFRs are widely expressed by many normal cell types and in certain cancers, tumours can be over-expressed or under-expressed (Franson & Lapka, 2005; Viele, 2005). The amount of EGFR that is expressed by a tumour can be measured by reliable laboratory testing. Overexpression of EGFR is associated with an advanced tumour stage, more aggressive tumours, a