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Yr 2 EOYS > Cancer EOYS3 > Flashcards

Cancer EOYS3 Flashcards

1
Q

Name a drug that targets EGRF mutation [2]

A

Gefitinib or erlotinib

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2
Q

Tyrosine kinase receptors:

Name 4 key antibody targets that are GF receptors and / ligands

A

Epidermal growth factor receptor (EGFR)

HER2 (no ligand)

HER2/3 (ligand: HER2 can bind to HER3 – activates different pathway)

Vascular endothelial growth factor (VEGF)

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3
Q

State the two main approaches for targeted therapies [2]

A

Antibodies
Small molecules tyrosine kinase inhibitors

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4
Q

State difference in antibody and small molecule kinase inhibitors

A

Antibodies:
* high selectivity
* targets are often restricted to the cell surface
* require intravenous or subcutaneous dosing because of their large molecular weight
* Can be conjugated to cytoxic drugs

Small molecule kinase inhibitors:
* vary in selectivity
* Oral
* Bind- ATP binding sites
* Can potentially bind a wider range of extracellular and intracellular targets (> one kinase)

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5
Q

Describe the mechanism of antibodies [2] and SMKI [1]

A

Antibody:
* Produce antibodies that target extracellular part of tyrosine kinase receptor
* Inhibits ligand binding or causes the ligand to bind in an area that doesn’t cause dimerization

SMKI:
* Binds to ATP binding pocket & intracellular-P cant occur

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6
Q

State the overall three mechanisms of monoclonal antibodies [3]

A

Killing tumour cell directly

Killing tumour cells via an immune-mediated mechanism

Vascular or stromal ablation: VEGF antagonsim

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7
Q

Pertuzumab inhibits which receptor:

HER2
HER2/HER3
EGFR
VEGF

A

Pertuzumab inhibits which receptor:

HER2
HER2/HER3
EGFR
VEGF

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8
Q

Describe mechansim of trastuzumab emtansine (Kadcycla)?

A

Kadycycla is formed from the conjugate binding of Herceptin with DM1, which is an anti-microtubule agent

Drug is taken up by lysosome.

Within the lysosome: herceptin and DM1 dissociate and are released into cell

DM1 attacks cell tubule

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9
Q

What is first line treatment of HER2-positive breast cancer? [3]

A

Pertuzumab (HER2/HER3 blocker), in combination with trastuzumab (HER2 blocker) and docetaxel

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10
Q

What is second line treatment of HER2-positive breast cancer? [2]

A

Trastuzumab - emtansine (Kadcycla)

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11
Q

What is third line treatment of HER2-positive breast cancer? [2]

A

Trastuzumab-deruxtecan

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12
Q

Describe overall mechanism of Small Molecule Tyrosine Kinase Inhibitors (e.g. Tarceva)

A

Tarceva has similar structure to ATP

Binds to ATP binding pocket in the cell membrane causes competitive inhibition in ATP binding pocket-inhibit function of kinases

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13
Q

Explain what a second generation tyrosine kinase inhibitor is [1]

Name a second gen tyrosine kinase inhibitor for EGFR in NSCLC [1]

A

Drug for the new mutation of the tyrosine kinase receptor

Mutations associated with drug resistance to erlotinib so Osimertinib prescribed (fits the new ATP binding site)

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14
Q

Which cascade is perhaps the most important oncogenic driver of human cancers?

PI3 Kinase
MAP Kinase
KRAS
AKT

A

Which cascade is perhaps the most important oncogenic driver of human cancers?

PI3 Kinase
MAP Kinase
KRAS
AKT

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15
Q

Monoclonal antibodies and cancer therapy mechanisms:

Explain how killing tumour cells directly via monoclonal antibodies works [4]

A
  • Inhibit ligand binding
  • Or possible delivery of toxic payload
  • Signalling blocked
  • Apoptosis induced
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16
Q

Monoclonal antibodies and cancer therapy mechanisms:

Explain how killing tumour cells directly via an immune-mediated mechanism works [3]

A
  • Induction of phagocytosis
  • Complement-dependent cytotoxicity (CDC)
  • Antibody-dependent cell cytotoxicity (ADCC)
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17
Q

Monoclonal antibodies and cancer therapy mechanisms:

Explain how killing tumour cells directly via vascular or stromal ablation works [1]

A

VEGF antagonism

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18
Q

Cetuximab inhibits which receptor:

HER2
HER2/HER3
EGFR
VEGF

A

Cetuximab inhibits which receptor:

HER2
HER2/HER3
EGFR
VEGF

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19
Q

,

A

.

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20
Q

What are the two components of Trastuzumab emtansine (Kadcycla)? [2]

A

Herceptin (acts as the transporter)
AND
Anti-microtubule agent: DM1

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21
Q

What is the difference in mechanisms between Herceptin (Trastuzumab) alonve versus Trastuzumab emtansine (Kadcycla)

A

Trastuzumab alone stops growth of cancer cells by binding to the HER2 receptor

Trastuzumab emtansine undergoes receptor-mediated internalization (herceptin acts as the transporter) into cells, is catabolized in lysosomes where DM1-containing catabolites are released and subsequently bind tubulin to cause mitotic arrest and cell death

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22
Q

Which drug prevents the HER2/HER3 dimer from forming?

Trastuzumab
Pertuzumab
Cetuximab
Kadcycla

A

Which drug prevents the HER2/HER3 dimer from forming?

Trastuzumab
Pertuzumab
Cetuximab
Kadcycla

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23
Q

Which drug stops HER2 binding to another HER2

Trastuzumab
Pertuzumab
Cetuximab
Kadcycla

A

Which drug stops HER2 binding to another HER2

Trastuzumab
Pertuzumab
Cetuximab
Kadcycla

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24
Q

Name a small molecule tyrosine kinase Inhibitors [1]

A

Tarceva
(Erlotinib)

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25
Q

Name three pathways that are targets for kinase inhibitors [3]

A
  • Transcription
  • Receptor tyrosine kinase signalling
  • Proto oncogenes
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26
Q

How does HER2 resistance occur?

A

As tumours develop they acquire mutations.

With HER2: becomes truncated: extracellular part becomes truncated.

As a result, kinase activity is switched off (doesn’t need receptor activation to switch on intracellular pathway).

As a result Herceptin stops working as there is no binding sit

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27
Q

Name a AE of targeting VEGF [1] and EGFR [1]

A

VEGF: High blood pressure

EGFR: Slow wound healing and blood clotting

28
Q

This rash comes from which cancer drug? [1]

A

Trastuzumab - rash

29
Q

Describe the effects of HER2 on cardiomyocytes [1]

A

HER2 inhibits cardiomyocyte apoptosis [1]

30
Q

Describe the cardiotoxic effects of Trastuzamab [2]

A

Inhibits HER2 cardiomyocyte apoptosis

Get a decline in left ventricular function AND congestive heart failure

Need regular cardiac monitoring

31
Q

Explain a draw back of using antibodies as a targeted therapy [1]

A

Cannot pass the cell membrane and must be given IV

32
Q

What type of radiotherapy would be used for lesions requiring full dose to the surface (skin) to max 2-3cm depth meaningful treatment such as to the following areas:

Eyes
Skin lesions
Post op skin lesions
Benign conditions

A

Superficial KV photons

Only penetrates a few mm (good for skin lesions)

33
Q

LINAC based treatments utilise what as radiotherapy? [1]

A

Electrons

34
Q

LINAC Electron based treatments are used for lesions in where in body? [4]

A

Lesions requiring dose closer to the skin
Lesions on the skin – using bolus
Skin
Lymph node regions

35
Q

Where would LINAC based treatments: MV photons (mega voltage) [1]

What is dosing regimen like? [1]

A

More penetrative treatment and dose at depth

High dose radical treatments are fractionated (broken up into smaller daily treatments) to deliver treatment safely and avoid damage to adjacent normal tissues/organs

36
Q

What are stereotactic radiotherapy treatments? [1]

A

Higher dose treatments: smaller margins, closer monitoring

Often considered ‘radiosurgery’, very targeted

37
Q

What is brachytherapy?

A

Using radioactive seed or implant to deliver targeted radiotherapy

38
Q

Brachytherapy can be used in which locations? [2]

A

Prostate – implanted radioactive seeds which deposit dose into prostate tissue

Cervix – radioactive seed Ir192 introduced via rods inserted through the tumour/cervix. Treatment plan created to calculate dwel l time of seed at various positions to deposit dose before removing.

39
Q

What is neoadjuvant chemotherapy? [1]

A

Treatment given as a first step to shrink a tumor before the main treatment is given

40
Q

What is adjuvant chemotherapy? [1]

A

after primary treatment with surgery or radiotherapy

41
Q

What is concomitant chemotherapy? [1]

A

Given at the same time as radiotherapy

42
Q

What is the most common platinum agent used for chemotherapy in concomitant therapy? [1]

A

cisplatin given with radiotherapy for SCC- acts as a radiosensitiser in many cases

43
Q

Which type of cancers can chemotherapy act as curative treatment for? [1]

A

Germ cell tumours (testicular, ovarian, mediastinal)

44
Q

What is neo-adjuvent chemotherapy? [1]

Name a cancer that is common for [1]

A

Chemotherapy given prior to surgery / radiation: improves patient fitness and operations are smaller / less invasive

Ovarian cancer

45
Q

What is adjuvent chemotherapy? [1]

Give an example of a cancer that its used on [1]

A

Given after radiation / surgery: eradicates evasive cancers

Breast cancer

46
Q

Name 6 modes of chemotherapy administration [6]

A

Topical
Subcut / IM
Oral
Intra-arterial
Intra-cavity
Intrathecal
IV

47
Q

Types of chemotherapy

Describe how alkylating agents work

A

Highly reactive molecules which bind to electron-rich nucleophilic moieties on all large and small molecules

No specificity but the chance reaction with DNA forms basis of anti-tumour effects

48
Q

Give 3 examples of alkylating agent chemotherapy [3]

A

Cyclophosphamide
Ifosfamide
Busulfan

49
Q

Name a common AE of alkylating agent [1]

A

hemorrhagic cystitis: condition in which the lining of the bladder becomes inflamed and starts to bleed.

50
Q

Types of chemotherapy

Describe MoA of platinum agents [1]

A

Primary mode of cell death is damage to cellular DNA by the development of covalent adducts

51
Q

Give 3 examples of planitum agent chemotherapies [3]

A

Carboplatin
Cisplatin
Oxaliplatin

52
Q

Types of chemotherapy

Describe MoA of anti-metabolites [2]

A

Most antimetabolites are structural analogs of molecules that are normally involved in the process of cell growth and division

They are incorporated into DNA and/or RNA and interfere with synthesis by conveying false messages

53
Q

Give an example of anti-metabolites [1]

A

Methotrexate (derivate of folic acid)

54
Q

Types of chemotherapy

Describe MoA of TOPOISOMERASE INHIBITORS [1]

A

DNA Topoisomerases (I & II) are essential enzymes that regulate the topological state of DNA during cellular processes such as replication, transcription and chromatin remodeling.

55
Q

Name examples of two topoisomerase I and II [4]

A

Topoisomerase-I
* Irinotecan
* Topotecan

Topoisomerase-II
* Doxorubicin
* Epirubicin

56
Q

Which of the following is cardiotoxic and cause dilated cardiomyopathy

  • Irinotecan
  • Topotecan
  • Doxorubicin
  • Epirubicin
A
  • Irinotecan
  • Topotecan
  • Doxorubicin
  • Epirubicin
57
Q

Types of chemotherapy

Describe MoA of tubulin active agents [1]

What are the two types? [2]

Give two examples of each type [4]

A

Microtubules are a core component of mitotic spindle that separates chromosomes during eukaryotic cell division

Vinca Alkaloids prevent assembly of microtubules and at higher doses inhibit mitotic spindle formation:
* Vinblastine
* Vincristine

Taxanes bind to microtubules; promotes assembly into microtubles and inhibits disassembly
* Paclitaxel
* Docetaxel

58
Q

Name the 4 misellaneous chemotherapy drugs and explain their MoA [4]

A

MISCELLANEOUS

Bleomycin
Mixture of cytotoxic glycopeptide antibiotics isolated from the fungus streptomyces verticillus that possess both anti-tumour and anti-bacterial properties however exact mechanism of action is unknown

Actinomycin-D
Another antibiotic from streptomyces parvullus; it exerts cytotoxic effects by intercalation between guanine-cytosine base pairs with inhibition of the synthesis of messenger RNA

L-Asparaginase
Contains the enzyme L-asparaginase originally isolated from escherichia coli; anti-tumour effect results from rapid and complete depletion of asparagine in the bloodstream and extracellular space which deprives tumour cells of the required amino acids and inhibits protein synthesis

Trabectedin
Derived from ecteinascidia turbinata; binds to the minor groove of DNA, bending the helix towards the major groove, which leads to interference with the intracellular transcription pathways and DNA-repair pathways

59
Q

Name drugs that target each stage of the cell cycle (G1 / S / G2 / M)

A

* G1: vinblastine
* S: Methotrexate, 6-Mercaptopurine, 5-fluorouracil
* G2: Bleomycin, etoposide, topotecan, daunorubicin
* M: vincristine, vinblastine, paclitaxel, docetaxel

60
Q

Name some general side effects of chemotherapy [7]

A

Nausea, vomiting, mouth ulcers, change in taste, diarrhea, constipation
Fatigue
Bleeding, bruising and risk of life-threatening infection
Rash, skin changes, nail changes
Change in liver function, cardiac function, lung function, renal function
Neuropathy, tinnitus
Early menopause, loss of libido and infertility
Blood clots
Hair loss
Allergic reaction

61
Q

Which chemotherapy drug would cause Palmar-Planter Erythrodysesthesia?

Capecitabine
Bleomycin
Doxorubicin
Imatinib

A

Which chemotherapy drug would cause Palmar-Planter Erythrodysesthesia?

Capecitabine
Bleomycin
Doxorubicin
Imatinib

62
Q

Which chemotherapy drug would cause Pulmonary Fibrosis?

Capecitabine
Bleomycin
Doxorubicin
Imatinib

A

Which chemotherapy drug would cause Pulmonary Fibrosis?

Capecitabine
Bleomycin
Doxorubicin
Imatinib

63
Q

Which chemotherapy drug would cause Raspberry Urine?

Capecitabine
Bleomycin
Doxorubicin
Imatinib

A

Which chemotherapy drug would cause Raspberry Urine?

Capecitabine
Bleomycin
Doxorubicin
Imatinib

64
Q

Which chemotherapy drug would cause Peri-Orbital Oedema?

Capecitabine
Bleomycin
Doxorubicin
Imatinib

A

Which chemotherapy drug would cause Peri-Orbital Oedema?

Capecitabine
Bleomycin
Doxorubicin
Imatinib

65
Q

Which chemotherapy drug would cause Flagellate Erythema ?

Capecitabine
Bleomycin
Doxorubicin
Imatinib

A

Which chemotherapy drug would cause Flagellate Erythema ?

Capecitabine
Bleomycin
Doxorubicin
Imatinib

Yr 2 EOYS (58 decks)

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