Part 1 – Answer the following 4 questions (worth 10% each):
Please limit to a single page per answer.
Explain why DNA repair is a critical tumor suppressor function. Using an example tumor suppressor gene, detail how it impacts a specific DNA repair mechanism. Classify its impact in at least one cancer/cancer syndrome, and present an actual or theoretical therapeutic strategy for treating patients with this syndrome
You are a clinician-scientist that has a patient with colon cancer. Identify four possible oncogenes that are both commonly affected in colon cancer and are actionable for treatment with available drugs either directly or indirectly. Identify two appropriate FDA-approved kinase inhibitor drugs for counteracting the gain of function for each of these four oncogenes. Identify which of the most common cancer-inducing amino acid mutations on these four oncogenes you would initially screen for (3 mutations for each oncogene) in your patient to identify which kinase you will target with a drug that you would first prescribe for your patient. (You may find the www.onconet.ca, www.kinasenet.ca, www.drugkinet.ca and http://cancer.sanger.ac.uk/cosmic websites as well as the lecture notes helpful.)
Prostate cancer is exquisitely dependent on androgens for growth and survival.
1. Describe the endocrine regulation of androgen levels by the hypothalamic pituitary axis.
2. Describe the androgen/androgen receptor signalling pathway
3. Name two molecular targets for treatment of prostate cancer and how drugs that target these proteins work to block androgen dependent growth of prostate cancer
A patient with renal failure underwent a kidney transplant using an organ obtained from the victim of a car crash. Six months later the patient was diagnosed with a malignant lesion in the donated kidney that the pathologist determined to be of lung origin. Subsequent investigation revealed that the organ donor had been successfully treated with radiation for lung cancer several years earlier.
A) In terms of the prevailing model of cancer immune surveillance, explain the history of the cancer from its origin in the donor to its re-emergence in the transplant recipient. (8 marks)
B) The treating physicians discussed withdrawal of immune suppression as a possible treatment strategy. Explain the potential benefits and downsides of this treatment from an immune perspective. (2 marks)