Neoplasia IV Flashcards
What does genomic instability lead to in tumours?
Heterogeneity
-tumour cells are different from each other, develop subclones as don’t repair DNA properly, don’t die when damaged and proliferate more
True of false: epithelial changes don’t need any changes before they can metastasize
False, they need many changes before metastasis.
Some cell types (hematopoietic, melanocytic) require fewer changes because they are natively able to spread.
What is the sequence of regular cells to metastasis?
Expansive avascular (no blood supply) -> expansive angiogenic (once get blood supply can grow more) -> genomic instability (tumour progresses, becomes worse) -> invasive vascular -> metastatic
Define heterogeneity
The development of considerable mutation and diversification of cellular phenotypes.
What are some complications with heterogeneity?
-diagnostic markers (variation cell to cell makes it hard to diagnose)
-chemotherapeutic regimens and drug resistance
(targeting tumour cells won’t work as well if not expressing target, cells becoming more heterogeneous may be resistant to chemo)
What does immunohistochemistry do?
Identification of poorly differentiated tumours. They identify particular proteins characteristic of a cell type. This can be a problem when tumours are heterogeneous for expression of these markers
How can cancer cells become independent of growth factors?
In ligand dependent firing, the ligand binds to the receptor and this signals downstream for the cell to divide. If there is no ligand, the receptor is not active. That is the normal process. The mutant receptor is ligand independent where even with no ligand, the receptor still signals downstream for the cell to divide.
Or, the cancer cell makes a growth factor that it doesn’t normally make and this signals the cell to keep dividing, autocrine signalling.
How do cancer stem cells enable replicative immortality?
Stochastic model is random, any cell could form a new tumour. This is unlikely, most cells grow a bit but unlikely to grow whole tumour again from a few cells.
CSC cancer stem cell if you enrich for CSC, regrow then you have a tumour with heterogeneity.
Treatment targeting the bulk of the tumour population might miss the precursor cells that have a different proliferative phenotype. New methods that target the stem cell pool might be more effective in depleting the tumour of its cells.
What are the defined characteristics of cancer stem cells?
- low proliferation rate
- low uptake of drugs
- ability to self renew and produce daughter cells
- often express stem cell markers
- context/microenvironment is important (eg the stem cell niche where nearby cells help keep in a stem cell state)
What characteristics of cancer stem cells allow them to be drug and radiation resistant?
- low proliferation rate
- low uptake of drugs
True or false: specifically targeting cancer stem cells might prevent tumour recurrence
True
What does telomerase do in cancer?
In cancer cells, expression of the telomerase enzyme lets them add back missing bits of telomeric DNA.
Normally, polymerase can’t finish replicating DNA so telomeres get shorter in successive generations. They get so small that the ends become sticky, they stick to each other and then the DNA becomes damaged and removed.
Why may there be regions of necrosis in the middle of tumours?
In tumour regions of hypoxia, tumour grows so creates more hypoxia, outgrows blood supply and this can lead to necrosis in the middle.
What does abnormal metabolism of cancer cell cause?
Leads to high ROS, which can kill the cells. Antioxidants are produced to deal with this, but tend to only result in a partial balance of high oxidative stress. This may lead to cancer cell survival along with the potential of ROS mediated mutagenic events that can drive cancer malignancy.
What is most cancer mortality due to?
Metastasis
