Which oncogene, implicated in hormone-unresponsive breast cancer, can be treated with Trastuzumab?
c-Kit is an example of what kind of oncogene
growth factor oncongene
What is the most common oncogene family? What is the normal function of the gene product?
RAS - small GTPases involved in cell signal transduction
K-RAS is commonly defective in what type(s) of cancer?
pancreas and colon
H-RAS is commonly defective in what type(s) of cancer?
bladder and kidney
c-ABL is implicated in what cancers? What is the genetic defect?
CML and ALL
t(9;22) balanced translocation
C-MYC is implicated in what type of cancer?
N-MYC is implicated in what type of cancer?
Describe the normal function of the RB gene
Tumor suppressor gene: binds and suppresses E2F
Describe the normal function of APC
Tumor suppressor gene
Normally helps destroy beta-catenin. Beta catenin normally activates TCF, a transcription factor promoting cell proliferation
Mutation of APC is associated with many adenomas
What is Familial Adenomatous Polyposis (FAP)?
A form of cancer featuring 100's of colon polyps
Caused by APC mutation
What is Li-Fraumeni Syndrome?
Inherited mutation in the p53 gene, causing a 25x increased chance of cancer by age 50
BAX is what type of protooncogene? BCL-2?
- Pro-apoptotic gene
- Anti-apoptotic gene
What is CYPIAI and why is it clinically significant?
CYPIAI activates polycyclic aromatic hydrocarbons (PAHs), which are highly carcinogenic. 10% of caucasians have a highly-inducible form of CYPIAI which increases activation of PAHs and therefore increases risk of carcinogensis.
What enzyme is responsible for detoxification of PAHs?
50% of caucasians have deletions in genes expressing this enzyme and therefore can't effectively detoxify PAHs, increasing carcinogenic risk
What are promoters? Give an example.
Promoters exacerbate (increase proliferation of) carcinogenic damage, but do not directly cause it.
Examples: hormones, alcohol.
What is Xeroderma Pigmentosum?
A predisposition to skin cancer due to a defect in DNA nucleotide excision pathway (DNA repair)
Name two general types of radiation damage and give some common cancers associated with each
- Ionizing: thyroid, lung, breast, leukemia
- UV: BCC, SCC, melanoma
Burkitt Lymphoma is associated with what type of infection?
Name the low-risk HPV types. Name the high-risk HPV types
- Low-risk: 6, 11
- High-risk: 16, 18, 31, 33
What is the general mechanism for Hepatitis B oncogenesis?
HBx gene suppresses p53 (tumor suppressor) and activates growth factor expression
What morphologic feature of tumor angiogenesis is a key driver of metastasis?
Cellular 'holes' in vasculature due to incomplete pericyte coverage of tumor vessels
Describe the function of the following VEGF receptors:
- vasculogenesis, angiogenesis
- vasculogenesis, lymphangiogenesis
Which VEGF receptor is primarily responsible for lymphangiogenesis?
What cell type do PDGF receptor inhibitors target? Why is this important?
Removal of pericytes makes vessel endothelial cells more vulnerable to anti-VEGF therapy