Cancer Flashcards
Where are the main checkpoints within the cell cycle?
During G1 - Check cell has enough resources to go into cell division
Just before mitosis (G2) to check for DNA damage
Spindle assembly checkpoint
Name 2 things that must occur for mitosis to proceed in each cell cycle checkpoint.
G1 - Need enough growth factor and nutrition
G2 - DNA has to properly replicated and organelles have to properly replicated
Spindle assembly checkpoint - Attachment of spindle fibres to kinetochore and correct alignment of sister chromatids at the midline of the cell
State 4 specific features of apoptosis (as opposed to necrosis
Requires ATP No inflammation Regulated No cellular disruption Apoptosis can be physiological; necrosis is only pathological
Why can we give antioestrogens to treat breast cancers?
Around 70-80% of breast cancers are oestrogen receptor positive, with oestrogen stimulating the growth of the cancer. By targeting these oestrogen receptors and antagonising them, it would prevent the cancer from spreading and continuously growing. Some oestrogen receptor negative cancers also respond to antioestrogens (around 5-10%)
Tamoxifen is not strictly antioestrogenic. Give 3 other benefits of it in breast cancer treatment apart from its anti-cancer properties
Improves bone density therefore reducing risk of osteoporosis
Doesn’t cause atherosclerosis by decreasing LDL cholesterol
Doesn’t have many S/E
Why can we use antiandrogens in some prostate cancers
Cancerous prostate cells may present androgen receptors which would stimulate growth of the cancer when androgens bind
How does giving GnRH treat cancers and why would we combine this therapy with antiandrogens in prostate cancer
GnRH constantly stimulating the receptor subsequently leads GnRH receptor desensitisation and down-regulation. As a result, this would cause less FSH and LH release, leading to less formation of testosterone and other androgens by the gonads, therefore reducing total circulating androgen concentration.
The adrenals also produce androgens, which the GnRH agonists do not decrease the concentration
What can staging be used for
To see how far the cancer has spread
Name 3 cytological features looked for in staging
Tumour size
Lymph node involvement and which lymph nodes
Number of lymph nodes involved and which lymph nodes
Metastasis
4 ways to assess the grade of a cancer
Degree of differentiation
Increased nuclear:cytoplasmic ratio
Presence of necrosis
No. of abnormal mitosis
List two cancers and state how they affect physiological function specifically
Lung cancer causes ectopic ACTH leading to Cushings Syndrome
Pituitary adenoma causing bilateral hemianopia
Prostate pushing against urethra and causing difficulty urinating
Colon cancer causing iron deficiency anaemia
Give reasons why prostate specific antigens are elevated in prostate cancer
PSA is a component of seminal fluid, and normally is prevented from entering the blood via the basement membrane and basal cell layer. However, due to damage to the basement membrane and basal cell layers due to the prostate cancer, it causes there to be PSA which enters the blood, leading to the rise in PSA in cancer
Give some treatment methods for prostate cancer
GnRH agonist – continuously bind to the GnRH receptor on Gonadotrophic cells, leading to receptor downregulation and decreased release of LH and FSH. As a result, there would be less stimulation of the testes to form testosterone and other androgens, leading to decreased growth of the prostate cancer, as the cancer is initially androgen dependent
Anti-androgens – prevent androgens from binding to the androgen receptor and having their subsequent effect, leading to decreased cancer growth
What is androgen independence
Androgen independence is a severe stage in prostate cancer where there is growth of the cancer despite endocrine therapy being used, occurring on average around 13 months after diagnosis
Give three causes of androgen independence
Receptor responding to the lower concentrations of androgen or other androgens
Receptor responding to other compounds similar to androgen, like oestrogen
Decreased levels of co-repressors of the receptor
Ligand-independent activation of the androgen receptor
Name four things that causes a normal cell to become cancerous
Uncontrolled proliferation
Cell-cell adhesions downregulated
Cells develop motility
Increased levels of matrix metalloproteinase (MMP)
Name four cytotoxic drugs and briefly describe what they do
Chlorambucil – alkylating agent: donates alkyl group to guanine residues leading to crosslinking of DNA strands and preventing DNA uncoiling at replication
Cisplatin – pseudoalkylating agent: similar to above but donates platinum residue instead of alkyl group
Methotrexate – antimetabollites. Masquerade purine or pyramidine residues and inhibit DNA synthesis and cause DNA double stranded breaks and apoptosis and inhibit de novo nucleotide synthesis
Doxorubican – anthracycline: Inhibit transcription and replication by intercalating into DNA
Vinca alkaloids and taxanes – Vinca alkaloids prevent assembly of spindle fibres; taxanes prevent disassembly of the spindle fibres
Irinotecan/topotican and etoposide – topoisomerase inhibitors: therefore allowing permanent DNA strand breaks
State four ways of resistance to cytotoxic drugs
Drug efflux from cell increased by ATP binding casket transporters
Reduced drug influx into cell
Increase DNA base repair to remove DNA adducts
Upregulate DNA repair mechanisms
State two reasons why the cell cycle might terminate.
DNA damage during replication causing apoptosis of the cell
Incomplete spindle attachment during metaphase (metaphase-anaphase checkpoint) => mitotic arrest
Lack of nutrient and growth factors needed for growth
Name the two families of cell cycle inhibitors
INK4 – displace cyclin D from cdk 4/6
CIP/KIP – bind to cdk complex therefore preventing cyclin binding
