Define the ‘four Rs’ of radiation oncology and outline how each contributes to
the response of the tumour and normal tissues during fractionated radiation
therapy
3. Mechanisms of carcinogenesis include genetic and epigenetic events. In regard to
genetic events, mutagens can arise from both external carcinogens and intrinsic
mutations.
Answer all parts of this question:
a) For each category below identify two (2) examples of carcinogens and one (1)
veterinary or human tumour associated with this carcinogen.
i. chemical carcinogens (2 marks)
ii. physical carcinogens (2 marks)
iii. viral infection. (2 marks)
b) Using specific examples, discuss the mechanisms by which cellular oncogenes
become activated and tumour suppressor genes become inactivated. Give
specific examples of oncogenes and tumour suppressor genes in your answer.
(18 marks)
c) Briefly explain the difference between a ‘gatekeeper’ and ‘caretaker’ tumour
suppressor gene. (2 marks)
d) Pathologic epigenetic events contribute to carcinogenesis.
i. Define an ‘epigenetic event’. (1 mark)
ii. Identify and briefly describe the mechanisms for the two (2) main
epigenetic events involved in carcinogenesis. (3 marks)
Continued over page
Veterinary Oncology Paper 1 Page 6 of 9
4. Radiation biology
Answer all parts of this question:
a) Define the ‘four Rs’ of radiation oncology and outline how each contributes to
the response of the tumour and normal tissues during fractionated radiation
therapy. (10 marks)
b) Oxygen is essential to radiation-induced cell kill. Explain the influence of
molecular oxygen on radiation-induced cell death. (2 marks)
c) Explain the concepts of ‘acute’ (or cyclic) and ‘chronic’ hypoxia, and provide
one (1) therapeutic option to overcome each. (6 marks)
d) Describe one (1) molecular and one (1) imaging method to measure tumour
hypoxia. (2 marks)
e) Discuss the function of the hypoxia-inducible family (HIF) of proteins. Indicate
the target genes induced by HIF proteins and their impacts on tumour
progression. Explain how HIF can become dysregulated in tumours and give
two (2) medical therapies that are clinically used to combat tumours with HIF
dysregulation. (10 marks)
Continued over page
Veterinary Oncology Paper 1 Page 7 of 9
5. Hallmarks of cancer
Answer all parts of this question:
a) List Hanahan and Weinberg’s original six (6) ‘hallmarks of cancer’, as
described in 2000. (6 marks)
b) List Hanahan and Weinberg’s two (2) emerging hallmarks and the two (2)
enabling characteristics subsequently identified in their 2011 review paper.
(4 marks)
c) Describe the steps required for a cancer to invade and metastasise. (10 marks)
d) Briefly define and discuss the ‘seed and soil’ hypothesis, including any
potential molecular explanation for this hypothesis. (5 marks)
e) Explain the role ‘ezrin’ plays in veterinary cancer. Include in your answer
one (1) example of a veterinary tumour type. (5 marks)
6. The ‘cell cycle’ is the series of events that take place in a cell associated with its
division and duplication (replication).
Answer all parts of this question:
a) Draw a diagram of the cell cycle in the supplied answer book and include
information about what is happening in each stage of the cycle. (6 marks)
b) In a few sentences, define the term ‘restriction point’ and explain the role that
the retinoblastoma (Rb) protein plays in regulating this phase of the cell cycle.
(3 marks)
c) Define the following terms in relation to the stage of the cell cycle in which
each class of drug is acting, and provide one (1) example of a
chemotherapeutic agent for each of the three (3) categories:
i. cell cycle phase – non-specific (1 mark)
ii. cell cycle phase – specific (1 mark)
iii. cell cycle – non-specific. (1 mark)
Question 6 continued over page
Veterinary Oncology Paper 1 Page 8 of 9
d) Describe the interaction between cyclins and cyclin-dependent kinases (CDK),
with respect to the cell cycle. Provide two (2) examples of cyclin/CDK
interactions. (6 marks)
e) Discuss the ways in which neoplastic cells can uniquely exploit the cell cycle.
(12 marks)
7. Diagnostic cytopathology: cytologic evaluation of neoplasia plays a critical role in the
clinical decisions of veterinary oncologists.
Answer all parts of this question:
a) Discuss the ways in which evaluation of cytologic samples can be used in
clinical practice, including important advantages and limitations of cytologic
evaluation of fine needle aspiration samples. (15 marks)
b) Identify differential diagnoses for round cell tumours encountered in dogs and
cats and describe cytological features used to differentiate these neoplasms.
(15 marks)
8. Effective anti-cancer chemotherapy is underpinned by theoretical considerations
based on tumour biology, as well as knowledge of the pharmacology of the agents
used.
Answer all parts of this question:
a) For a tumour in which, theoretically, 99% of the cells are killed per cycle of
chemotherapy, state the number of cycles of chemotherapy required to reduce a
tumour burden of 1,010 cells to less than one cell. (1 mark)
b) Define the fractional cell-kill hypothesis and identify the principal
pharmacologic factors affecting the results of treatment. (3 marks)
c) The fractional cell-kill hypothesis rarely, if ever, applies in practice to the
treatment of solid tumours. Outline three (3) main reasons for this and briefly
indicate how each cause might be circumvented. (13 marks)
Question 8 continued over page
Veterinary Oncology Paper 1 Page 9 of 9
d) Pharmacokinetic factors influence the therapeutic and/or adverse effects of
chemotherapy drugs. Briefly discuss the pharmacokinetic factors that might
cause the following clinical situations. Explain how these situations could,
theoretically and/or in practice, be avoided or corrected.
Answer all parts of this sub-question:
i. Grade 3 or 4 myelotoxicity has been observed on each of two separate
occasions after a cat has been treated with carboplatin at 200 mg/m2
.
(4 marks)
ii. A dog with multiple myeloma being treated with oral melphalan at the
recommended dose rate has neither myelotoxicity nor a response to
therapy after two weeks of daily treatment. (5 marks)
iii. A dog with clinical stage 4 lymphoma has grade 4 myelotoxicity seven
days after its first dose of vincristine at 0.5 mg/m2
. (4 marks)
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