Molecular Biology and Cancer Prevention, Detection and Therapeutics Flashcards
Give three examples of DNA viruses and the tumours they may give rise to
- Papovavirus family - give rise to warts (benign) or carcinoma of the uterine cervix
- Hepadnavirus family e.g hepatitis B virus - liver cancer (hepatocellular carcinoma)
- Herpesvirus family - give rise to nasopharyngeal carcinoma or Burkitt’s lymphoma
Give two examples of RNA viruses and the tumours they may give rise to
Retrovirus family; adult T-cell leukaemia/ lymphoma
Human immunodeficiency virus; Karposi’s sarcoma
Retroviral oncogenes are
genes ‘hijacked’ from host cells. A typical retrovirus does not contain any oncogenes. However, cellular genes can be acquired when the viral genome inserts/ excises from a host genome. They become overactive, as they are now under control from viral promoters
Explain how DNA virus oncogenes work on permissive hosts and what their requirements are in order to get their own DNA copied.
DNA viruses require their host to be actively proliferating in order to get their own DNA copied. For this purpose they carry unique genes whose products interfere with the cell cycle’s control mechanisms.
This is not a problem for the host as it is going to be killed by lysis, however in non-permissive hosts, oncogenes persist.
The effect of DNA viruses on
a) permissive host cells
b) non-permissive host cells
Which of the two leads to transformation?
a) When a virus infects a natural, permissive host, it replicates, causes cell lysis and releases progeny virus particles
b) In a non-permissive host, virus replication is blocked. Virus becomes permanently inserted into the host genome
NON-PERMISSIVE
Mode of action of DNA virus oncogenes is to..
bind two of the most critical tumour suppressors of mammalian cells:
p53 and pRB
What is p53 responsible for?
Involved in cell cycle arrest or apoptosis following DNA damage
What is pRB involved in?
controlling the transcription of cyclin E and A at the restriction point
What are two tumour suppressors?
p53 and pRB
Rb protein binds to what, rendering it inactive?
At the same time, p53 protein activates safety brake on cell proliferation.
cell proliferation factor
DNA virus oncogenes bind to _____ suppressors. They sequester ___ and _53, thus activating the cell proliferation factor and thus allowing gene transcription and cell proliferation to occur
tumour
Rb
p
Papillomavirus uses two viral proteins __ and ___ to sequester the host cells p53 and Rb respectively
E6
E7
CAUSES OF CERVICAL CANCER: HPV infections (common) can either be a transient (most are cleared) or \_\_\_\_\_\_\_ infection. Need to have a \_\_\_\_\_\_\_ infection for aroun 10-20 years with a \_\_\_-\_\_\_\_ strain in order to develop \_\_\_\_\_\_\_\_ cancer. Other risk factors such as \_\_\_\_ and \_\_\_\_\_\_\_\_\_ also play a role.
persistent. high-risk cervical. age at infection immunological factors
What allows for detection of cervical cancer to be detected early?
Routine cervical smears
What are the three results from cervical smears? - normal, precancerous lesion and invasive carcinoma
Normal: cells large and well differentiated
Precancerous lesion: Cell differentiation and proliferation is abnormal but lesion is not yet invasive, Cells are in different stages of differentiation, some quite immature.
Invasive carcinoma: All cells undifferentiated with scanty cytoplasm and relatively large nucleus
What is a papilloma virus vaccination to prevent cervical cancer? Which HPV types does it protect against. How long is it the protection effective for?
Gardasil
HPV 6 and 11 (cause 90% of genital warts)
HPV 16 and 18
at least 8 years after completion of the three-dose course,
Other than routine cervical smears, what is another method of cancer prevention/ early detection. When would this be carried out? Knowledge of carrier status can be used to inform?
Susceptibility genes If you have a family history of particular types of cancer e.g. BRCA-related breast cancer or familial colon cancer. - screening - chemoprevention - prophylactic surgery
Why is it important to know the genotype of a tumour?
Targeted therapies only work if..
Knowing where the tissue of origin or whether a cancer is benign or malignant does not tell us about their characteristics/ how they behave and how to kill them. Tumours from the same origin can be genetically diverse and therefore behave in different ways.
The genetic profile of a tumour can tell us a lot about cell behaviour and therefore can inform both prognosis and treatment choice.
Targeted therapies will only work if the tumour actually possess the oncogene variant they target.
How can some cancers become drug resistant?
Mutations in drug target (CML?imatinhib)
Mutations in genes in associated pathways (metabolising enzymes)
TUMOUR GENOTYPING
You can use genomic, ________ and proteomic profiles to determine:
transriptomic
- classify the tumour according to mutation profile
- associate this profile with the ‘aggressiveness’ of the cancer and draw conclusion about the patients prognosis and best way to treat the tumour
- Predict which treatment the tumour will best respond to
