Question 1
Question
Primary resistance: No [blank_start]response[blank_end] to administration
Acquired resistance: Initial [blank_start]regression[blank_end] –> tumour reappears –> patient [blank_start]relapses[blank_end]
Caused by
- Alterations in drug [blank_start]metabolism[blank_end]
- Modifications to [blank_start]drug target[blank_end]
Answer
-
response
-
regression
-
relapses
-
metabolism
-
drug target
Question 2
Question
Resistance mechanisms:
1. Reduced drug [blank_start]uptake[blank_end]
E.g. MTX uptake via reduced folate carrier
2. Alteration of [blank_start]intracellular[blank_end] drug targets
e.g. Production of DNA TopII with resistance to [blank_start]anthracyclines[blank_end]
3. Decreased drug concentration ([blank_start][blank_end] prodrug activation)
e.g. high GST levels inactivate [blank_start]cisplatin, alkylating agents[blank_end]
4. Increased [blank_start]removal[blank_end] of drug
e.g. P glycoprotein and multidrug resistance-related protein with [blank_start]vincas, taxanes, anthracylines[blank_end]
Answer
-
uptake
-
intracellular
-
anthracyclines
-
decreased
-
cisplatin, alkylating agents
-
removal
-
vincas, taxanes, anthracylines
Question 3
Question
Where do resistant cells come from?
Theory 1: Only [blank_start]resistant[blank_end] cells survive therapy, and repopulate tumour.
Theory 2: Mutations present post-therapy are [blank_start]naturally selected[blank_end] for.
Combined model: Escape from [blank_start]normal[blank_end] growth control, [blank_start]mutations[blank_end] present, over time we see structural/biochemical
[blank_start]abnormalities[blank_end], cytotoxic therapy then causes resistance.
Sensitive drugs with shorter lifespans are therefore [blank_start]less[blank_end] prone to resistance.
Answer
-
resistant
-
naturally selected
-
normal
-
mutations
-
abnormalities
-
less
Question 4
Question
Apparent resistance: Tumour can be sensitive but not show a clinical response due to incorrect [blank_start]scheduling[blank_end]. The interval is too [blank_start]long[blank_end]. Cell-cycle specific agents with short [blank_start]t1/2[blank_end] needed.
Anatomical [blank_start]isolation[blank_end] also causes apparent resistance; ALL (acute lymphoblastic leukemia) relapse in children due to failure to penetrate [blank_start]BBB[blank_end].
Answer
-
scheduling
-
long
-
t1/2
-
isolation
-
BBB
Question 5
Question
Chemo principles:
Principle 1: Treat [blank_start]rapidly[blank_end]. [blank_start]Radiation/surgery[blank_end] with chemo as an adjuvant successfully only in breast cancer and in children.
Principle 2: Treat with a [blank_start]combination[blank_end]. Use drugs with different [blank_start]targets[blank_end]. Will have different unwanted effects - though note there is additive [blank_start]efficacy[blank_end] not [blank_start]toxicity[blank_end]. Alternating regimens [blank_start]decreases[blank_end] toxicity.
Question 6
Question
Endocrine Therapy Principles:
Cellular proliferation is influenced by hormones.
• [blank_start]Oestrogen[blank_end] – female breast, endometrial carcinoma
• [blank_start]Androgen[blank_end] – prostate
There is tumour regression following [blank_start]ovariectomy[blank_end].
Answer
-
Oestrogen
-
Androgen
-
ovariectomy
Question 7
Question
Hormonal sensitivity in breast cancer depends on genes, estrogen receptors and growth factor receptors.
• ER+ means there will be [blank_start]response[blank_end] to therapy
• ER+ AND PgR+ increases your chance of [blank_start]remission[blank_end]
Also carry growth factor receptors (GFRs).
Inverse correlation:
High ER content = few [blank_start]GFRs[blank_end]
High GFR content = few [blank_start]ERs[blank_end]
Answer
-
response
-
remission
-
GFRs
-
ERs
Question 8
Question
Choose the incorrect statement.
Answer
-
High estrogen favours growth factor synthesis.
-
Hormone therapy goal is to prevent formation of growth factors.
-
Growth factors lead to mitosis and a reduction in estrogen receptors.
Question 9
Question
Oestrogen receptor antagonists e.g. Tamoxifen, clomiphene citrate, nafoxidine
- [blank_start]Selective[blank_end] estrogen receptor modulators (SERM)
- [blank_start]Competitively[blank_end] binds to oestrogen receptors
• Oestrogenic effects (inhibit [blank_start]bone[blank_end] resorption, stimulates [blank_start]PgR[blank_end] synthesis)
• Anti-oestrogenic effects (breast tissue, inhibits synthesis of [blank_start]GF[blank_end])
Example: Tamoxifen, for [blank_start]recurrent, metastatic[blank_end] breast cancer. Is an adjuvant/[blank_start]prevention[blank_end]. Metabolised by CYP2D6, 3A4, metabolites have [blank_start]long[blank_end] t1/2. Unwanted Effects: [blank_start]hot[blank_end] flushes, nausea, amenorrhoea, [blank_start]vaginal[blank_end] bleeding
Answer
-
Selective
-
Competitively
-
bone
-
PgR
-
GF
-
recurrent metastatic
-
prevention
-
long
-
hot
-
vaginal
Question 10
Question
Aromatase inhibitors e.g. Anastrozole, Letrozole, Exemestane (steroid)
Aromatase converts androgens to [blank_start]oestrogen[blank_end]; this is the primary mechanism of BC in [blank_start]post[blank_end] menopausal women, so we can inhibit it. For [blank_start]advanced[blank_end] breast cancer. No value if patient is [blank_start]premenopausal[blank_end]. SEs: Stiffness, [blank_start]joint[blank_end] pain, loss of bone mineral [blank_start]density[blank_end] (osteoporosis, bone fractures).
Answer
-
oestrogen
-
post
-
advanced
-
premenopausal
-
joint
-
density
Question 11
Question
Carcinoma of the prostate:
Androgens modulate by:
• Growth of prostatic [blank_start]epithelium[blank_end]
• Production of prostatic [blank_start]fluid[blank_end]
• [blank_start]Most[blank_end] prostate cancers arise from epithelium
3 main approaches:
1. Remove [blank_start]primary[blank_end] source
2. Block hormone [blank_start]synthesis[blank_end] (*5 alpha-reductase)
3. Androgen R [blank_start]antagonists[blank_end]
Answer
-
epithelium
-
fluid
-
Most
-
primary
-
synthesis
-
antagonists
Question 12
Question
Lowering androgen levels
1. [blank_start]Surgically[blank_end] (orchidectomy)
2. Chemically using synthetic [blank_start]gonadotrophin[blank_end] releasing hormones - [blank_start]GnRH and LHRH)[blank_end] analogues e.g. goserelin, leuprorelin. Causes initial [blank_start]flare[blank_end] (high [blank_start]LH and FSH[blank_end]) = Downregulation of GnRH [blank_start]receptors[blank_end], loss of sensitivity, suppress [blank_start]androgen[blank_end] formation. Unwanted effects: sexual [blank_start]dysfunction[blank_end], hot [blank_start]flushes[blank_end], growth of [blank_start]breast[blank_end] tissue
Answer
-
Surgically
-
gonadotrophin
-
GnRH and LHRH
-
flare
-
LH and FSH
-
receptors
-
androgen
-
dysfunction
-
flushes
-
breast
Question 13
Question
Antiandrogens e.g. Flutamide can [blank_start]inhibit[blank_end] flare.
• [blank_start]Selective[blank_end] antagonist
• Prevents [blank_start]testosterone[blank_end] binding to [blank_start]nuclear[blank_end] androgen receptors in [blank_start]prostate[blank_end]
Have no effect on [blank_start]pituitary[blank_end] function and so fewer side effects.
Answer
-
inhibit
-
Selective
-
testosterone
-
nuclear
-
prostate
-
pituitary