Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Y2S2 > Cancer Chemotherapy > Flashcards

Cancer Chemotherapy Flashcards

1
Q

Name the 9 Hallmarks of cancer:

A

*Sustaining Proliferative Signalling
*Evading growth suppressors
*Resisting cell death
*Enabling replicative immortality
*Inducing angiogenesis
*Activating invasion and metastasis
Deregulating cellular energetics
Avoiding immune destruction
Tumour promoting inflammation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What should be the steps involved before initiating cancer treatment?

A

Self detection/ referral - 2 weeks max to see specialist
Diagnosis- staging, histology/genetics
Surgery/ radiotherapy/ chemo or supportive care

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Name and describe 4 classes of treatment for cancer:

A

Curative- aggressive treatment
Palliative- given to prolong life and reduce symptoms
Concomitant- studying the medicine (trials)
Subsequent line- one line of therapy up until a point e.g side effects

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What does palliative mean?

A

Means not going to cure, can survive for many years

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Name and describe the two classes of curative treatment for cancer:

A

Neoadjuvant- given before surgery to decrease tumour size
Adjuvant- given after surgery or with radiotherapy to ‘mop up’ dry cancer cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Name types of systemic therapy:

A

IV, IM, SC or oral

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Name types of regional therapy:

A

Intrathecal (spine), intra-arterial, intravesical

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What are important considerations to make when choosing a chemotherapy drug for a patient?

A

Performance status
Age
Previous treatment
Co-morbidities
Polypharmacy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What is performance status?

A

From 0-5
0 is best
5 is death
4 is not well at all
2-3 is bed bound/ can do activities

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What is cytotoxic chemotherapy?

A

Anti-proliferative, inhibit cell division
Acts on all cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Name 3 cytotoxic drug targets:

A

Chemistry of nucleic acids
DNA or RNA production
Mechanics of cell division

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Why is combination therapy used in chemotherapy and the advantages:

A

Drugs with a different MoA, targets multiple pathways
Reduce toxicity of one class (as all low doses)
Each drug to be active alone on tumour type
Increase efficacy
Overcome drug resistance

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What occurs in drug resistance for chemotherapy?

A

Leads to discontinuation and progression
Decrease drug influx
Increase drug efflux
Inactivation of apoptotic pathways
Altered drug targets
Mutation of targets
Increase metabolism so deactivation (Cyp450)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Describe hormone therapy as a type of therapy against cancer:

A

Remove the hormone that feeds the cancer to grow
Block the hormone
e.g Tamoxifen or enzalutamide (prostate cancer)
Not cytotoxic so not chemotherapy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Describe how Bevacizumab fights against cancer:

A

Monoclonal antibody
Selectively binding to VEGF (vascular endothelial GF) so inhibits VEGF from binding to receptor

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Describe how Herceptin fights against cancer:

A

Monoclonal antibody
Selectively targets the extracellular domains of the HER2 protein
HER2 is a tyrosine kinase and an oncogene which provides the cell with potent proliferative and anti-apoptosis signals

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Why are antibody drug conjugates used and give an example:

A

Can use a monoclonal antibody to target HERT2 amplification
Attach to a very cytotoxic drug (so doesnt cause death)
Ado-trastuzumab Emtansine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

How are immune checkpoint inhibitors used as a chemotherapy?

A

Re-train the immune system
Blocks PDL1 or PD1 so allows T cell to kill cancer

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What are the benefits of oral chemotherapy?

A

◦ Home treatment
◦ Patient satisfaction
◦ Chair time
◦ Pharmacist role
◦ Less invasive

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What are the challenges of oral chemotherapy?

A

◦ Poor adherence
◦ Absorption - diet
◦ Polypharmacy – interactions
◦ Side effects

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Name a tyrosine kinase inhibitor:

A

Imatinib

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

How do tyrosine kinase inhibitors work?

A

Targets the abnormal BCR-ABL1 (tyrosine kinase) protein that causes uncontrolled CML cell growth and blocks its function causing it to die

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What is CML?

A

Chronic Myeloid Leukaemia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What are the side effects of chemotherapy?

A

*N&V
*Hair loss
*Diarrhoea
Mucositis (throat and mouth sores)
Constipation
Rash
Fatigue
Hypersensitivity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

What are the two types of Chemo Induced N&V (CINV) and describe the onset of action:

A

Peripheral pathway (most common)- instant vomiting/ effects
Central pathway- delayed phase few days later

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

Describe how CINV occurs:

A

Chemo enters the enterochromaffin cell of the GI tract and it releases serotonin
Bind to 5HT3 receptor on vague affrent and causes side effects

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

How is CINV prevented/ stopped?

A

Using a 5HT3 antagonist such as ondansetron, anything ending in ‘setron’

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

What are the risk factors for CINV?

A

Female
Non-smoker
Opioids
Age
Type of surgery
Migraine
Obesity
Lots of others

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

What are the complications in CINV?

A

Dehydration
Electrolyte disturbance
Nutritional deficiency
Oesophageal tears
Chemo dose delays
Aspiration pneumonia- going into lungs so risk of infection
Quality of life

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

Name and describe the types of CINV:

A

Acute- in 24 hours
Delayed- more than 24 hours
Breakthrough- CINV despite prophylaxis
Anticipatory- prior to admin of chemo
Refractory-CINV despite appropriate measures

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

Describe the treatment used for different types of CINV:

A

Acute- metoclopramide, domeridone, 5HT3 antagonists
Delayed- dexamethasone, NK1 antagonists
Breakthrough- 5HT3, NK1
Anticipatory- lorazepam
Refractory- levomepromazine, NK1, nabilone- not often used due to SEs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

Name 3 types of chemotherapies that will very likely cause CINV:

A

Cisplatin
Dacarbazine
Carmustine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

Name 3 types of chemotherapies that will not likely cause CINV:

A

Bevacizumab
Chlorambucil
Vincristine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

What is mucositis?

A

Sore or ulcerated mouth or throat
Mucosal cells of mouth and GI tract are sensitive to chemo
From dryness to ulcers
Causes discomfort and pain
Takes 7-14 days to resolve

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

What are the preventative measures for mucositis?

A

Regular brushing- using a soft brush
Avoid floss and electric toothbrushes
Rinse mouth regularly-with salt water
Avoid alcohol containing products
Delay dental procedures if possible
Avoid spicy/ acidic foods

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

What is the pain treatment for mucositis?

A

Local anaesthetic mouthwashes or lozenges
Gentle mouthwash
Ice
Analgesics - paracetamol

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

What is the infection treatment for mucositis?

A

Treat by looking at clinical characteristics/ cultures
-fungal, systemic fluconazole or nystatin mouthwash
-viral, acyclovir

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

Name 3 high risk chemotherapy agents that cause diarrhoea and what do they treat?

A

5-fluorouracil
Capecitabine
Irinotecan
Colorectal and breast cancer

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

Name non-pharmacological interventions for chemotherapy induced diarrhoea:

A

Oral rehydration (8-10 glasses a day)
Dietary modifications
Small frequent meals

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
40
Q

Name pharmacological interventions for chemotherapy induced diarrhoea:

A

Loperamide- 1st line
Oral antibiotics
Severe cases= hospitalisation, IV fluids and electrolytes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
41
Q

What is irinotecan chemotherapy used for and what side effects does this have?

A

Treatment of metastatic colorectal cancer
Early and late onset diarrhoea can occur

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
42
Q

Describe the treatment for delayed diarrhoea in irinotecan chemotherapy:

A

Occurs after 24 hrs (3-10 days after)
Loperamide 4mg then 2mg every 2 hours until diarrhoea free for 12 hours
Ciprofloxacin 250mg BD for 7 days if lasts longer than 24 hrs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
43
Q

What is anticholinergic syndrome in irinotecan chemotherapy?

A

Inhibition of acetylcholinesterase
Increases sweating, saliva, stomach cramps and diarrhoea
SC atropine 300mcg or as prophylaxis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
44
Q

What are the causes of constipation with cancer?

A

Chemo- cisplatin, vinca alkaloids,
Supportive care- opioids, ondansetron
Other- inactivity, dietary changes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
45
Q

What advice should be given for the prevention of constipation?

A

Fluids (6-8 glasses)
High fibre foods
Excerise

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
46
Q

What is the treatment for constipation?

A

Laxatives
Review medication (last resort as not changed as much as if it was diarrhoea)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
47
Q

Describe how chemotherapy can cause myelosuppression:

A

RBCs: anemia, fatigue
WBCs: risk of infection, neutropenia
Platelets: thrombocytopenia, easily bruised, may bleed longer than usual

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
48
Q

Describe febrile neutropenia:

A

Fever, often with other sign of infection with a pt who has neutropenia
Requires urgent treatment with empirical antibiotics

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
49
Q

What is febrile neutropenia caused by and how would you prevent it?

A

As a consequence of myelosuppressive chemo
Prevent with:
-prophylactic antibiotics
-G-CSF prophylaxis
-Dose reductions

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
50
Q

What is the definition of febrile neutropenia?

A

Temp of more then 38ºC and absolute neutrophil count of less then 0.5 x 10^9/l

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
51
Q

What is GCSF and how is it used?

A

Granulocyte colony stimulating factor
Stimulates production of neutrophils
Daily SC injections for 5-7 days following myelosuppressive chemo

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
52
Q

Give two examples of GCSF medications:

A

Figrastim
Lenograstim

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
53
Q

What are the indications of GCSF?

A

Chemotherapy with more than 20% risk of FN
Continuing chemo following episode of FN

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
54
Q

What are the risk factors of febrile neutropenia?

A

Severe symptoms
Hypotensive
COPD symptoms
Leukaemia treatment
Dehydrated
More than 60 yrs old
Inpatient

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
55
Q

If they are low risk, what is the treatment of neutropenic sepsis?

A

Oral antibiotics:
-ciprofloxacin
-co-amoxiclav
Iv stat then PO
Outpatient treatment or short admission

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
56
Q

If they are high risk, what is the treatment for neutropenic sepsis?

A

Urgent empirical IV:
-Tazocin
-Ceftazidime
Admission
Review after 48 hours to see if can take orally

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
57
Q

What is the advice given to help the side effect fatigue?

A

Move around and exercise when you can
Limit activities
Eat healthily
Drink plenty of fluid

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
58
Q

What is the dermatological side effect of capecitabine?

A

Hand foot syndrome (57%)
Palms of hands/ soles of feet, tingling, redness, numbness, pain and swelling

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
59
Q

What is the prevention of the dermatological side effect of capecitabine?

A

Avoid tight fitting shoes
Rubbing
Hot water
Moisterisers

60
Q

What is the treatment for the side effect of capecitabine?

A

Lanolin containing creams
Dose reductions

61
Q

Describe the severity of hand foot syndrome from capecitabine:

A

Grade 1- Numbness, dysesthesia and paresthesia, painless swelling, discomfort of hands and feet not effecting activities
Grade 2- painful erythema and swelling of hands and feet and discomfort, affecting activities
Grade 3- Moist desquaminiation, ulceration, blistering, severe pain, preventing work or performance of ADLs

62
Q

What is Cetuximab used for?

A

EGFR inhibitor
Antibody to epithelial growth factor receptor
Treatment of colorectal and head and neck cancer

63
Q

What is Erlotinib used for?

A

EGFR inhibitor
EGFR specific tyrosine kinase inhibitor
Treatment of lung cancer

64
Q

What are the dermatological side effects of EGFR inhibitors?

A

Can cause severe papulopustular eruptions

65
Q

Describe the treatment for EGFR inhibitor skin reactions:

A

Mild- topical antibiotic cream/lotion (clindamycin)
Moderate- Add topical steroid (hydrocortisone)/ oral antibiotics (doxycycline)
Severe- dermatology reference, dose reduction, consider stopping treatment if all else fails

66
Q

What are long term side effects of chemotherapy?

A

Cardiac
Thromboembolic
Secondary cancers
Infertility
Respiratory

67
Q

What is extravasation?

A

Accidental leakage of chemo from vein into surrounding tissue
Irritants
- inflammation
-pain
Vesicants
-necrosis
-pain
-blistering

68
Q

Describe the different grades in a hypersensitivity reaction to chemotherapy?

A

Grade 1= transient flushing or rash, drug fever less than 38ºC
Grade 2= rash, flushing, urticaria, dyspnea, drug temp more than 38ºC
Grade 3= symptomatic bronchospasm with or without urticaria, oedema, angioedema, hypotension
Grade 4= anaphylaxis
Grade 5= death

69
Q

Describe the pre-medication needed for patients when taking chemotherapy to stop hypersensitivity reactions:

A

Dexamethasone 20mg po every 6 hours for 4 doses
Ranitidine 150mg po every 8 hours for 3 doses
Chloramphenamine 4mg po every 6 hours for 4 doses

70
Q

Where can molecules bind in DNA including DNA?

A

Proteins bind to major groove
Small molecules bind to minor groove via π, H- bond and electrostatic
DNA interacts by π-π stacking

71
Q

Name four types of classical chemotherapies:

A

DNA Alkylators
Topoisomerase Inhibitors
Anti-mitotics
Anti-metabolites

72
Q

Name a type of DNA Alkylator and how do they work against cancer?

A

Nitrogen mustards
They cross link DNA
Stops DNA polymerase being able to separate strands
The most predominant cross link is the N7 of guanine on two strands- inter strand crosslink

73
Q

Name and describe the two types of cross linking and which one works as a chemotherapy?

A

Intrastrand (same strand)
Interstrand (different strand)
Interstrand crosslinking has been correlated with antitumour potency

74
Q

What are SN1 reactions?

A

Nucleophilic substitution
Rate determining step is unimolecular (one molecule involved)- the loss of the leaving group
The rate ONLY depends on the conc of substrate

75
Q

What are SN2 reactions?

A

Nucleophilic substitution
Rate determining step is bimolecular (two molecules involved)
The rate depends on the conc of the substrate AND the nucleophile

76
Q

Describe the steps in the DNA Alkylation mechanism:

A

The nitrogen mustard forms an aziridinium ion (SN2 like- intramolecular substitution)
The aziridinium ion alkylates the N7 of guanine
The second Cl may then be displaced to form a second aziridinium ion (SN2) and the process repeats

77
Q

Name 4 types of currently used nitrogen mustards:

A

Alkyl mustard
Aniline mustard
Melphalan (L-PAM)
Chlorambucil

78
Q

Describe Cyclophosphamide as a nitrogen mustard:

A

It is a nitrogen mustard prodrug
Activated in the cellular environment, more by what a cancer cell has and a normal cell doesnt

79
Q

How is acrolein produced?

A

A toxic product from the formation of a N mustard from cyclophosphamide

80
Q

How does acrolein carry out its function?

A

Reacts with cysteine residues in proteins via Micheal addition
S-alkylation of cysteine thiols via acrolein leads to protein inactivation

81
Q

Describe the mechanism of resistance in Nitrogen mustards and how is this over come?

A

Increased expression of glutathione-S-transferase and levels of glutathione
Increased expression of excision repair enzymes
Changes in drug uptake
May be countered by co-administration of glutathione-S-transferase inhibitors

82
Q

Describe a DNA platinating agent and what does it help kill?

A

DNA Alkylator
Cisplatin is the most frequently used antitumour drug in the clinic
Used in the treatment of testicular, ovarian head and neck, lung and bladder cancers

83
Q

Describe the mechanism of action of cisplatin:

A

The positively charged aquated platinum(II) reacts with biological nucleophiles
The biological target is thought to be N7 of guanine
95% of adducts are intrastrand crosslinks which are thought to inhibit DNA polymerase

84
Q

How does resistance occur in DNA platinating agents?

A

Increased repair mechanism for intrastrand crosslinks
Increased expression of thiol containing proteins (glutathione, metallothionein)

85
Q

What is DNA intercalation?

A

Causes the shape of the DNA helix to distort
This causes problems for DNA processing enzymes
This prevents cell replication and leads to cell death

86
Q

Name an example of a Topoisomerase Inhibitors and how does it work?

A

Anthracyclines
DNA intercalators
Planar, aromatic structure sits between bases and interacts through π-π stacking
Amino sugar binds into the minor groove
Hydrogen bonds can be formed to the DNA bases

87
Q

Name four types of anthracyclines:

A
  • Doxorubicin
  • Daunorubicin
  • Idarubicin
  • Epirubicin
88
Q

What are the different side chains for the different anthracyclines?

A

1=bottom left 2=top right
Doxorubucin- OCH3, OH
Daunorubicin- OCH3, H
Idarubicin- H, H
Epirubicin- OCH3, OH

89
Q

What are the functions of DNA topoisomerase I and II?

A

Release the strain in DNA during replication by cutting the strands, then reforming them
Topoisomerase I cuts one strand of DNA
Topoisomerase II cuts two strands of DNA

90
Q

Describe the mode of action of topoisomerase II:

A

Topoisomerase II binds two double helices
Double strand break in one helix – covalent bonds are formed between TopoII and the broken DNA phosphate backbone
The full helix gets passed through the broken helix
DNA stands are released and the double strand break ligated back together, releasing its covalent bond to TopoII

91
Q

Describe the mechanism of action of anthracyclines:

A

The intercalation distorts the shape of the double helix
Anthracyclines inhibit DNA Topoisomerase II by preventing it from fixing the double strand break
Most antitumour intercalators inhibit this enzyme

92
Q

What is Mitoxantrone and what is it used for?

A

Topoisomerase II inhibitors
DNA intercalation through π-π stacking
Hydrogen bonding with DNA bases
Used in leukaemias, lymphomas and advanced breast and prostate cancer

93
Q

How does resistance occur in topoisomerase II inhibitors?

A
  • Increased expression of P-glycoprotein
  • Increased efflux from the cell
94
Q

What is an orthosteric inhibitor?

A

A molecule that binds into the active site of a protein, preventing its activity

95
Q

What are the functions of microtubules?

A

They pull apart the chromosomes during mitosis and meiosis
Provide structural support

96
Q

Name two ways in how anti-mitotics work:

A

Anti-mitotics target the microtubules in cells:
-Disruption of microtubule assembly
-Inhibition of microtubule disassembly

97
Q

Describe how anti-mitotics cause disruption
of microtubule assembly?

A

They bind to free αβ-tubulin dimers
They disrupt the balance between polymerisation and depolymerisation
Results in the dissolution of microtubules and the destruction of mitotic spindle
In healthy cells this leads to cell cycle arrest
In cancer cells this leads to death by catastrophic mitosis

98
Q

Name examples of anti-mitotics which causes disruption microtubule assembly and describe the difference:

A

Vinca alkaloids:
-Vinblastine (amine) at physiological pH can be protonated
-Vincristine (amide) not protonated and slighlty more potent

99
Q

How do anti-mitotics cause inhibiton
of microtubule assembly?

A

Stabilisation of microtubules and prevention of their disassembly prevents cell replication
Leads to the formation of abnormal bundles of microtubuli

100
Q

Name examples of anti-mitotics which causes inhibition microtubule assembly and describe the difference:

A

Paclitaxel (Taxol) ππ stacking (aromatic), only HBA, has amide
Docetaxel (Taxotere) no aromaticity, HBD+HBA, has carbamate and more soluble

101
Q

How can resistance occur in anti-mitotics?

A
  • Overexpression of p-glycoprotein
  • Mutations in tubulin gene
102
Q

What are the functions of antimetabolites in chemotherapy?

A

Toxic analogues of essential precursors for macromolecules (e.g DNA/RNA)
-Inhibit essential enzymes
-Disrupt the formation of macromolecules

103
Q

What is folic acid important for in DNA?

A

Formation of pyrimidine bases

104
Q

Describe how pyrimidine antimetabolites work:

A

5-FU is incorporated into RNA and DNA – less into DNA as it’s a uracil analogue
In RNA a disruption of function is observed
Intramolecular interactions may be affected by disruption of base pairings

105
Q

Describe Capecitabine as an antimetabolite:

A

A prodrug of 5-FU
It is activated by three enzymes to release 5-FU

106
Q

Describe how folate antimetabolites work and give an example:

A

Competitive inhibition of dihydrofolate reductase, e.g methotrexate
The affinity of Methotrexate for dihydrofolate reductase is
1000-fold that of folic acid
Methotrexate cannot be reduced by dihydrofolate reductase
Inhibits the synthesis of DNA, RNA, thymidylates and proteins

107
Q

What is the difference between methotrexate structure and folic acid?

A

OH into NH2
NH to the left into NCH3

108
Q

Name 2 types of modern chemotherapy and why are they modern?

A

NIBs- Tyrosine kinase inhibitors
RIBs- PARP inhibitors
Don’t target all proliferating cells

109
Q

What does PARP stand for?

A

Poly(ADP)Ribose Polymerase

110
Q

How is PARP involved in cells?

A

Involved in DNA repair
Fixes single strand breaks e.g. those caused by Topoisomerase I

111
Q

What is the function of BRCA1 and BRCA2 and what occurs if these are mutated?

A

Genes that produce proteins that help repair DNA damage
They are involved in repairing double strand breaks
Mutations in cancers result in proteins that cannot repair double strand DNA damage
Often seen in breast and ovarian cancers

112
Q

How can PARP inhibitors be involved with mutated BRCA genes?

A

If PARP is inhibited, single strand breaks cannot be repaired
Results in DNA with lots of single strand breaks
During proliferation, this leads to double strand breaks
These are either repaired by homologous recombination (HR) in normal cells or lead to cell death in BRCA mutated cells

113
Q

Name and describe a BRCA PARP inhibitor:

A

Olaparib
Used to treat advanced ovarian, fallopian tube and peritoneal cancers that carry faulty BRCA1 or 2 genes
Cyclopropylamide increased oral bioavailability
Conversion to piperazine increased both cell permeability and potency

114
Q

Describe the BCR-ABL fusion protein and where is it found?

A

BCR and ABL are two genes, usually found on chromosome 9 and chromosome 22 respectively
Translocation of the ABL and BCR genes form the Philadelphia chromosome
Gene product is a protein that is always on
It acts as a tyrosine kinase and promotes proliferation
Found in chronic myelogenous leukaemia

115
Q

Why could the BCR-ABL fusion protein be a target for a tyrosine kinase inhibitor?

A

Unique to cancer, as healthy cells don’t have this or are over expressed in the tumour than healthy cells

116
Q

Name and describe a BCR-ABL kinase inhibitor:

A

Imatinib
Introduction of the methyl group introduced selectivity for ABL kinase, but insoluble in water
Introduction of piperidine gave the molecule water solubility

117
Q

Name three other ABL-Kinase inhibitors:

A

Dasatinib
Nilotinib
Bosutinib

118
Q

What is BRAF?

A

Signalling pathway that promotes cell proliferation, gene expression, mitosis, cell survival, differentiation and apoptosis

119
Q

How can a mutation in the BRAF protein cause cancer?

A

Many melanomas contain mutations in the B-Raf protein
Single amino acid mutation: V600E to a glutamic acid
This mutation allows for downstream signalling without upstream activation
Results in uncontrolled cell proliferation

120
Q

Name and describe BRAF inhibitors including their selectivity:

A

Sorafenib- Approved for kidney and liver cancer, not selective for BRAF
Vemurafenib- Approved for melanoma, selective for BRAF
Dabrafenib- Approved for metastatic melanoma, selective for BRAF

121
Q

Why would you replace an isopropyl in a drug to a terbutyl?

A

So it can’t be oxidised which is better
As isopropyl find metabolites and very quickly changed which might be toxic

122
Q

What does an IC50 and GI50 mean?

A

Lower IC50 (nm)= hitting target better
Lower GI50 (nm)= getting into cells better

123
Q

How can resistance occur to tyrosine kinase inhibitors?

A

Small mutations in target protein can prevent the binding of the kinase inhibitor
In lung cancer, the EGFR receptor undergoes a T790M mutation which reactivates the pathway by preventing the binding of the TKI
Other pathways can be upregulated to promote cell proliferation and survival

124
Q

Name two tyrosine kinase inhibitors:

A

BCR-ABL and BRAF inhibitors

125
Q

Give the features of a carbocation:

A

Very electrophilic
Very reactive
Very little formed

126
Q

How is cisplatin changed in vivo?

A

Chlorine ligands are displaced in vivo by water molecules

127
Q

Describe folic acid metabolism:

A

Folic acid reduced by dyhydrofolate reductase into tetrahydrofolate
Methylene from sereine forms methylenetetrahydrofolate
Which can can be picked up by thymidylate synthase to reform dyhydrofolate

128
Q

How does thymidylate synthase form dyhydrofolate?

A

Deoxyuracil monophosphate (dUMP) (methylenetetrahydrofolate) picks up a single carbon atom and converts it into deoxythymine monophosphate (dTMP) (dihydrofolate) using thymidylate synthase

129
Q

What can be used to inhibit thymidylate synthase?

A

dUMP looks like a base
5-fluorouracuil 5-FU can be used to inhibit dUMP
This forms 5FdUMP

130
Q

What type of nitrogens can be protonated?

A

Amine
Pyridine
Aniline

131
Q

What does T, N and M mean in staging of cancer?

A

Tumour size
Lymph Nodes
Metastasis

132
Q

Describe the TNM staging:

A

T1, less than 3cm
T2, more than 3cm
T3, any size but near airway
T4, any size but in air way
N0, no lymphs affected
N1-4 lymph nodes have been effected
M0, no metastasis
M1, metastasis

133
Q

Name the 4 cancer P’s:

A

Prediction
Prevention
Precision
Participation

134
Q

What would be the prediction for breast cancer?

A

Faulty BRAC1/2
Diagnostic tests
HER2

135
Q

What would be the prevention of breast cancer?

A

Weight management, alcohol consumption, contraceptive choice, physical activity, HRT
i.e. managing the risk factors for breast cancer development, breast feeding, smoking

136
Q

What is the participation of breast cancer?

A

Mammogram screening
Mastectomy
Quitting smoking, regular exercise

137
Q

What is a main risk factor for developing CML?

A

Radiation

138
Q

What are risk factors in developing colorectal cancer?

A

Eating too much processed and red meat
Eating too little fibre
Overweight or obese

139
Q

Name and describe the prediction of colerectal cancer:

A

Familial adenomatous polyposis (FAP)
If left untreated then likely to have cancer in 40’s, recommend to remove colon in 20’s
Lynch syndrome, or hereditary non polyposis colon cancer (HNPCC)

140
Q

Name the 4 main types of leukaemia:

A
  • Acute myeloid leukemia (AML)
  • Chronic myeloid leukemia (CML)
  • Acute lymphoblastic leukemia (ALL)
  • Chronic lymphocytic leukemia (CLL)
141
Q

Where does acute myeloid leukaemia start?

A

Starts from immature white blood cells called granulocytes or monocytes in the bone marrow

142
Q

What is the age range in AML?

A

More than 40% are over 75 but any age

143
Q

What are the main chemos for AML?

A

Cytarabine- anti metabolite
Daunorubicin- TOP II inhibitor

144
Q

Where does acute lymphoblastic leukaemia start?

A

Starts from lymphocytes in the bone marrow

145
Q

What is the age range in ALL?

A

Children 0-4
More common in females than males

146
Q

What is the age range in CLL?

A

Rare to have it in people aged less than 40
More common in men than woman

Y2S2 (14 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions