Quiz
ON5 Cytotoxic resistance and endocrine therapy
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Questions in this quiz (13)
1Primary 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]- Aresponse
- Bregression
- Crelapses
- Dmetabolism
- Edrug target
2Resistance 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]- Auptake
- Bintracellular
- Canthracyclines
- Ddecreased
- Ecisplatin, alkylating agents
- Fremoval
- Gvincas, taxanes, anthracylines
3Where 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.- Aresistant
- Bnaturally selected
- Cnormal
- Dmutations
- Eabnormalities
- Fless
4Apparent 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].- Ascheduling
- Blong
- Ct1/2
- Disolation
- EBBB
5Chemo 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.- Arapidly
- BPrimary radiation/surgery
- Ccombination
- Dtargets
- Eefficacy
- Ftoxicity
- Gdecreases
6Endocrine 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].- AOestrogen
- BAndrogen
- Covariectomy
7Hormonal 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]- Aresponse
- Bremission
- CGFRs
- DERs
8Choose the incorrect statement.
- AHigh estrogen favours growth factor synthesis.
- BHormone therapy goal is to prevent formation of growth factors.
- CGrowth factors lead to mitosis and a reduction in estrogen receptors.
9Oestrogen 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- ASelective
- BCompetitively
- Cbone
- DPgR
- EGF
- Frecurrent metastatic
- Gprevention
- Hlong
- Ihot
- Jvaginal
10Aromatase 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).- Aoestrogen
- Bpost
- Cadvanced
- Dpremenopausal
- Ejoint
- Fdensity
11Carcinoma 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]- Aepithelium
- Bfluid
- CMost
- Dprimary
- Esynthesis
- Fantagonists
12Lowering 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- ASurgically
- Bgonadotrophin
- CGnRH and LHRH
- Dflare
- ELH and FSH
- Freceptors
- Gandrogen
- Hdysfunction
- Iflushes
- Jbreast
13Antiandrogens 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.- Ainhibit
- BSelective
- Ctestosterone
- Dnuclear
- Eprostate
- Fpituitary
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- User has deleted their subject information Quiz on ON5 Cytotoxic resistance and endocrine therapy, created by Deleted user on 09/10/2019.
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