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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
