Learning Outcome: Explain the broad rationale for the use of different anticancer treatments including surgery,

cytotoxic chemotherapy, radiotherapy, hormone therapy and immunotherapy

I. Surgery
1. A patient will normally have their first consultation about a solid tumour with a surgeon.
a) Leukaemias and lymphomas are not able to be surgically removed. However, other invasive
procedures such as bone-marrow transplants, allogenic stem-cell transplants, and Autologous stem-cell
transplants are used
2. Surgeon assesses whether the cancer can be removed without the need for further treatment, or if
adjuvant/neo-adjuvant treatment is required.
3. Idea behind surgery is to remove the largest mass of mutated cells and effected lymph nodes. However, if
there is evidence of further metastasis then adjuvant treatment will likely be required
II. Chemotherapy
1. Chemotherapy drugs are directly cytotoxic, doing irreparable damage to DNA and cellular machinery
a) The theoretical justification for using chemotherapy is that cancer cells are rapidly dividing, and are
therefore more susceptible to cellular damage
b) The toxicity of these drugs requires a risk/benefit analysis to determine dosage, rounds of treatment ect.
2. Four major targets for Cytotoxic chemotherapy
a) DNA Damaging Drugs: Carry out irreparable damage to cell DNA, such as alkylation, cross-lining,
fragmentation
b) Inhibitors of metabolic pathways : Drugs that block the synthesis of essential biomolecules such as
purines, pyrimidines, and folates
c) DNA repair inhibitors: block the proper repair of DNA, either by intercalation into DNA helices or by
inhibiting repair/topological enzymes (TOPO 1 & 2)
d) Inhibit cell Division: Drugs that inhibit tubule formation from the centrioles, stalling cell division
3. Because chemotherapy aims to directly kill cancer cells, healthy cells are affected as their growth rates are
not much slower than that of cancer cells
a) The risk is even higher is tissues such as bone marrow, which are naturally quickly dividing
b) Side effects of chemotherapy are common and include: Nausea, damage to hair, fatigue, anaemia,
immunosuppression, cardiotoxicity, neurotoxicity
4. A major reason to use chemotherapy is the reduce the incidence of cancer recurrence
a) Chemotherapy is administered systemically with the intent of killing micrometastatic cells invisible to a
surgeon or radiologist
5. Resistance to chemotherapy is possible as some cancer cells express efflux pumps which remove cytotoxic
drugs from the cytosol
III. Radiotherapy
1. Radiotherapy is the utilization of ionizing radiation (focused X-rays & -rays) to cause irreparable DNA
damage and produce oxygen radicals which cause oxidative stress
a) The effectiveness of radiotherapy is often related to the oxygen levels in the tissue, as this relates to
the amount of free-radicals produced
b) Due to the above radiotherapy is variable effective depending on tissue-type
c) Side-effects also vary by tissue type
2. Can be used palliatively for pain relief and many other symptoms
3. Major side effects of long term radiotherapy includes an increased risk of leukaemia and lymphoma in later
life
IV. Hormone Therapy
1. Certain types of cancer cell express hormone and growth factor receptors in the cell or on the cell surface
responsible for stimulating the cell cycle
2. Inhibition of the receptor mediated pathways result in a stalling of cell growth and possibly apoptosis
3. Examples include the use of aromatase inhibitors and oestrogen mimics to starve breast carcinomas, or
inhibitors of EGFR

a) Note: mutations in second messenger genes many allow the pathway to act independently of the
receptor, making receptor targeted drugs less effective
4. Long term usage of hormone therapy is often recommended
5. Side effects of hormone deprivation include osteoporosis (for Estrogen receptor inhibitors)
V. Immunotherapy (Biologic Therapy)
1. Immunotherapy works by recruiting the host immune system to attack and destroy cancer cells, or by
causing direct cell death from an exogenous antibody
2. Immunotherapy is often more specific and often does not have the major side-effects that radiotherapy and
chemotherapy have.
3. Use of recombinant interferons and interleukins can be used to stimulate immune responses to both solid
and circulating cancer cells
a) Used for melanoma, renal carcinoma
b) Side-effects include flu like symptoms,
c) Not as effective at killing tumour cells as chemo or radiotherapy
4. Immunoregulatory drugs such as thalidomide affect angiogenesis and increase cytokine production have
been used in a variety of cancers
5. Engineered Monoclinal antibodies are the most common form of immunotherapy used in clinics today
a) These antibodies bind to receptors on the surface of cancer cells.
b) Damage to the cell may be caused by inhibition of receptor function, stimulation of an apoptotic
pathway, recruitment of immune cells to destroy the cancer cell, or sensitization of the cell to apoptotic
pathways following a cytotoxic event
c) Example: Herceptin
6. Monoclinal antibodies can be engineered to carry a cytotoxic agent with them, causing two-fold damage to
the targeted cell