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Flashcards in Pathophysiology of Cancer Deck (33)
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What are the two main differences between benign and malignant tumours?

Benign are not invasive, and cannot metastasize


What are the four steps of the cancer process?

1. Initiated cell - a mutation in a single cell
2. Promotion - initiated cell proliferation rate is high
3. Malignant conversion - there is a critical, irreversible mutation
4. Progression - progeny continue to mutate


What are the eight capabilities cancer needs to become invasive?

1. Self-sufficient in growth
2. Insensitive to growth
3. Can evade apoptosis
4. Can proliferate indefinitely
5. Have angiogenesis
6. Can metastasize and invade
7. Have cellular energy deregulation
8. Can avoid the immune system


What are common mutations to produce self-sufficiency in growth?

Oncogene activation to produce a tumours own growth system are often results of mutations in autocrine GF production, and over-expression of GF receptors.
Mutations in the tyrosine kinase signal transduction pathways can also lead to uncontrolled proliferation


What are common mutations for a tumour cell to become insensitive to growth inhibition?

These are often loss of function mutations in tumour suppressor genes i.e. the Rb pathway (pathway that extracellular anti-proliferative signals)


What are common mutations in cancer that allow them to evade apoptosis?

1. Increased hormone receptor expression increasing survival signal
2. Increased anti-apoptotic protein expression
3. Most common is they have a mutation in P53 tumour suppressor gene, inactivating it


What is the main mutation that creates cell immortalisation in tumours?

80-90% have increased telomerase expression, the enzyme that transcribes telomere repeats. This is another mechanism to prevent apoptosis


How do tumours become able to perform angiogenesis?

There is a shift in the balance of positive and negative signalling proteins involved in angiogenesis/neovascularization
(about as much as we need to know)


How do tumours evade the immune system?

They co-opt it, and use it to increase growth and encourage invasion


How does inherited Lynch syndrome contribute to cancer development?

Via a mutation in DNA repair genes (MSH2, MLH1, MSH6)


How does inherited Li-Fraumeni syndrome contribute to development of cancer?

A pre-existing mutation in TP53, a tumour suppressor gene


In which cancers are the DNA repair genes BRCA1 and BRCA2 implicated in?

Breast and ovarian cancers


Is chemotherapy usually used in conjunction with other treatments?



What are three ways in which chemotherapy is used in conjunction with other treatments of cancer?

1. Neoadjuvant - before surgery to shrink the tumour
2. Induction - given to reduce remission, common with leukemia
3. Definitive - to cure, mainly in early stage tumours that are chemo-sensitive


What are the 6 principles of Chemotherapy?

1. Specificity of cancer drugs
2. Kinetics of tumour growth and detection
3. Drug efficacy and fixed proportion killing
4. Drug efficacy and tumour regrowth
5. Cell cycle and susceptibility to specific drugs
6. Drug resistance


What are mechanisms of traditional chemotherapy drugs?

They are anti-proliferative and decrease tumour growth


What must a cancer drug have a kill % greater than, to effectively kill a tumour?

A drugs kill % must be greater than the cell number
E.G. a 99.999% kill rate will be effective with a tumour with


Following initial treatment, what are the three possible situations a tumour may be in?

1. Killed by the immune system's CD8+ T-cells leading to a cure
2. Still actively growing AKA residual disease eventually leading to reappearance
3. Becoming dormant for many years before reactivation


What is the classic mechanism of anti-cancer drugs, and give four examples of how they accomplish this
(Hint - one example is impaired synthesis of DNA bases)

Many anticancer drugs interfere with DNA synthesis and/or function, inducing apoptosis AKA cell death
1. Chemical damage to DNA
2. Impaired synthesis of DNA bases
3. Inhibition of transcription/translation
4. Disruption of cell division mechanisms


What is the mechanism of alkylating agents, and give an example of an alkyating agent?

Alkylating DNA at guanine bases (usually) to form DNA adducts, leading to strand breaks and cell death independent of the cell cycle
Examples: Nitrogen mustards, nitrosoureas


Which class of anticancer drugs are platinum-based drugs similiar to? Give an example of a platinum-based drug

Alkylating agents
Example - Cisplatin


What are two groups of the anticancer drugs Anti-metabolites, which phase of the cell cycle do these affect, and give an example of each type

-Folic acid antagonists i.e. Methotrexate
- DNA base analogues i.e. 5-Fluorouracil
This affect the S phase of the cell cycle


What are two groups of mitotic inhibitors?

-Those that interfere with the mitotic spindles
-Those that bind to microtubules to prevent their disassembly in mitosis


What are two groups of cytotoxic antibodies used to treat cancer?

1. Anthracyclines, which inhibit topoisomerase
2. Bleomycins, which induce single and double DNA strand breaks


What type of anticancer drug is Tamoxifen, often used to treat breast cancer?

It's a hormone based drug - it blocks estrogen receptors


What is a non-cell cycle phase dependent anticancer drug?

Alkylating agents


What are likely side effects of classical cancer drugs?

- GI: mouth ulcers, nausea (esp. alkylating agents), vomiting
- Hair loss (esp cyclophosphamide & platinum drugs)
-Myelosuppression (esp anti-metabolites & mitotic inhibitors)


How are newer targeted drugs for cancer different to classical ones?

-They are gentler and more specific
- Are in large part, tyrosine kinase inhibitors
- Can also be antibodies which attempt to block angiogenesis in tumours


How are newer chemotherapy drugs administered?

With classical ones


What is the biggest problem with newer anti-cancer drugs?

Resistance to the tyrosine kinase inhibitors - can develop within 6-7 months

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