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Oncology > Oncology Therapeutics Random > Flashcards

Oncology Therapeutics Random Flashcards

1
Q

Etoposide

A

Topoisomerase 2
Usually 2nd Line (After poor radiotx response)
Binds to DNA topoisomeraise II complex
Used in Testicular and Lung
Arrest cell in G2/M Phase = More Radiosensitive

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2
Q

Topotecan

A 
Topoisomerase 1
Usually 2nd Line
Prevents torsional relief in DNA 
Prevents religation of DNA
Increases Radiotherapy sensitivity of DNA
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3
Q

Vemurafenib

A

Inhibits cell proliferation in the setting of BRAF Mutation.

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4
Q

COX2

A

iNDUCIBLE ISOFORM THAT ACTIVATES PROTAGLANDIN PRODUCTION IN INFLAMMATORY CELLS.

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5
Q

FOLFOX

A

Oxaliplatin + 5FU/LV

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6
Q

Chimeric mAb

A

Consist of Fab regions from another species combined with the Fc portion of a human antibody, resulting in a construct that is approximately two thirds human.

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7
Q

IHC HER2 Scoring

A

IHC Scoring of Tumour with immunohistochemestry between 0-3

FISH+/-

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8
Q

Doxorubicin

A

Anti-Tumour Antibiotic
BREAST, ENDOMETRIAL AND OVARIAN (+Some Childhood)
Isolated from Stropomyces SPP

4x MOA’s

  1. Topomerase II inhibition
  2. High Affinity DNA intercalation
  3. Alteration of Membrane Fluidity
  4. Superoxide free radical damage. (cardiotoxic!)

Activation is by hydrOXYlation – Hence Cardiotoxic.

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9
Q

Targeted regional therapy for CRC liver Mets?

A

Hepatic arterial infusion

Floxuridine

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10
Q

Vincristine

A 
Vinca Alkaloid
Mainly Leukaemia. 
Bind to tubulin, preventing microtubulin formation. 
M-Phase specific. 
NEUROTOXIC
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11
Q

Mechlorethamine

A

Alkylating Agent

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12
Q

Thyroglobulin

A

Measurement only clinically useful in assessing recurrence of thyroid Cancer.

Suppressed TSH + elevated thyroglobulin suggests disease recurrence

Post-treatment thyroglobulin should be low (

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13
Q

Role of BRAF

A

Post RAS protein involved in signalling for cell growth.

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14
Q

Chlorambucil

A

Alkylating Agent

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15
Q

a-fetoprotein (AFP)

A

Used as a tumour marker in Hepatocellular carcinoma (HCC)/hepatoblastoma in children. Essentially junior albumin. Also: Germ cell teratomas of the testes/ovaries

Levels >20 mg/L prompt further investigation
Levels >200 mg/L suggestive of HCC
Levels >400 mg/L diagnostic of HCC

Also elevated in:
Pregnancy
Infancy
Non-malignant liver conditions e.g. cirrhosis, hepatitis, cholestasis

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16
Q

Trastuzumab

A

Mab against Her2 cell surface receptor
(binds to the extracellular domain of ERB2. Preventing extracellular activation of HER2 and signalling and flags cells for destruction by the imune system. Immune cells bind to trastuzumab and induce anti-tumour effect)
HER2+ Breast Cancer (Ajuvent & Metastatic Disease)
HER2+ Gastric Cancer
IV or Subcut

S/E
Cardiotoxicity (not dose dependent, regular ECG’s, do NOT GIVE with ANTHRACYCLINE)

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17
Q

Mitoxantrone

A

Anti-Tumour Antibiotic

Isolated from Stropomyces SPP

4x MOA’s

  1. Topomerase II inhibition
  2. High Affinity DNA intercalation
  3. Alteration of Membrane Fluidity
  4. Superoxide free radical damage. (cardiotoxic!)

Activation is by hydrOXYlation – Hence Cardiotoxic.

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18
Q

Brentuximab Verdotin

A

Group Iib mAb (only one approved).
Hodgkin Lymphoma
Targets CD30 antigen expressed in the tumours
Conjugared to MMAE

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19
Q

Tu prefix

A

Tumour.

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20
Q

Human chorionic gonadotrophin (hCG)

A

Elevated levels in germ cell tumours e.g. seminoma, teratoma, choriocarcinoma

Sensitive tumour marker

Screening:
Patients with molar pregnancies followed up for 6 months
Rising levels in absence of new pregnancy are diagnostic

Response to therapy:
Good response to chemo: 40,000 IU/L plus risk factors

Monitor treatment/disease recurrence
hCG levels should normalise and remain low

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21
Q

Group III Biotherapeutics

A

Protein Vaccines

• Eg HPV vaccine for prevention of HPV infection and associated cancers.

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22
Q

Cetuximab

A

mAb against EGF receptor (Anti-EGFR)
EGFR activated critical survival and evasion pathways.
EGFR overexpressed in 85% of CRC Tumours
Colorectal cancer (nsc lung and scc of head and neck)

If patient have RASH = BETTER OUTCOME!
Skin toxicity

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23
Q

Pertuzumab

A

HER2+ Brest Cancer
Prevents Dimerisation of HER2
Inhibits ligand activated dimerisation.

HER2+ Breast Cancer (Investigational)

Abnormal LFT’s

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24
Q

Trastuzumab Emtansine (T-DM1)

A

Trastuzumab (increases the therapeutic window of DM1)
+ DM1 = Potent Cytotoxic (targets microtubules)
Requires Stable Linker to keep bound

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25
Q

a’

A

Rat mAb

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26
Q

Group IV Biotherapeutics

A

Protein Diagnostics
• Eg GHRH used to diagnose defective GH secretion.
• Imaging agents for cancer – eg anti-PSA antibody used to detect prostate cancer

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27
Q

Gefitinib and Erlotinib

A

Small Molecule Kinase Inhibitors
MOA: EGFR inhibitors
Used in Non-responsive Non-Small Cell Lung Cancer

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28
Q

CVS risk of COX2 Inhibition.

A

MI, STROKE, VENOUS CLOTS.
Disruption of PG12 TxA2 balance = prothrombotic.
Best ine = paproxen.

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29
Q

COX2 inhibition S/E

A

CVS morbidity and mortality.

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30
Q

Key Mediators of Inflammation? Pathway that produces?

A

Prostaglandins.
Produced by the cycloxygenase pathway.
Inhibited mainly by NSAIDs

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31
Q

Epirubicin

A

Anti-Tumour Antibiotic

Isolated from Stropomyces SPP

4x MOA’s

  1. Topomerase II inhibition
  2. High Affinity DNA intercalation
  3. Alteration of Membrane Fluidity
  4. Superoxide free radical damage. (cardiotoxic!)

Activation is by hydrOXYlation – Hence Cardiotoxic.

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32
Q

STOP and GO?

A

NOT GOOD, DECREASED SURVIVIAL

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33
Q

Bleomycin

A

Anti-Tumour Antibiotic
LYMPHOMAS, GERM CELL CANCERS, H+Neck Cancers.
Isolated from Stropomyces SPP

4x MOA’s

  1. Topomerase II inhibition
  2. High Affinity DNA intercalation
  3. Alteration of Membrane Fluidity
  4. Superoxide free radical damage. (cardiotoxic!)

Activation is by hydrOXYlation – Hence Cardiotoxic.

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34
Q

Imantinib

A

Small Molecule Kinase Inhibitors
MOA: Bind Tyrosine Kinase
LYMPHOMAS AND LEUKAEMIAS

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35
Q

Lapatinib

A

Small Molecule INTRACELLULAR Kinase Inhibitor
Directly inhibits phosphorylation and activation of downstream pathways.
HER2+ Breast Cancer (After progression Trastuzumab)

S/E Rash

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36
Q

Methotrexate

A

Anti-Metabolites (– Folic Acid Antagonist)
Cell Cycle Specific (S-Phase)
Inhibits dihydrofolate reductase, depleteing tetrahydrofolate.
TOXIC TO BONE MARROW – Combine w/Folinic Acid

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37
Q

Humanized antibodies

A

Consist of only the CDRs from the foreign mAb, and are about 95% human.

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38
Q

Colorectal mAb’s

A

Cetuximab and Panitumumab

Bevacizumab

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39
Q

Irinotecan

A

Topoisomerase 1
Plant Alkaloid
Usually 2nd Line
MOA: prevents DNA unwinding by inhibiting topoisomerase 1, resulting in inhiition of both replication and transcription
Increases Radiotherapy sensitivity of DNA

TOXICITY = Steatohepatitis

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40
Q

Carbohydrate antigen 19-9 (CA 19-9)

A

Pancreatic Cancer Biomarker.

Prognosis: high pre-operative levels associated with poorer outcome than lower pre-operative concentrations

Recurrence: post-surgery considered with rising concentrations

41
Q

Idarubicin

A

Anti-Tumour Antibiotic

Isolated from Stropomyces SPP

4x MOA’s

  1. Topomerase II inhibition
  2. High Affinity DNA intercalation
  3. Alteration of Membrane Fluidity
  4. Superoxide free radical damage. (cardiotoxic!)

Activation is by hydrOXYlation – Hence Cardiotoxic.

42
Q

Carbohydrate antigen 125 (CA 125)

A

CA 125 raised in 90% of patients with advanced ovarian cancer. Used in screening for women >50yo with symptoms.

If serum CA 125 ≥ 35 IU/mL → ultrasound scan of the abdomen and pelvis
If CA 125

43
Q

Renal Effect of Prostaglandin/inhibition

A

Acute interstitial nephritis, haemodynamic nephritis. Often with nephrotic (heavy proteinuria) .

44
Q

COX1

A

Constant Housekeeper

  • Inhibits acid synthesis
  • Increases Blood flow
  • Stimulates constriction and clotting
45
Q

Naproxen

A

Long Acting
Non-COX selective
Propionic Acid

46
Q

Cisplatin and Carboplatin

A

Platinum Analogues
Reactive complex that cross links guanine units in DNA.
Used in Ovarian and Tesisticular C
CISPLATIN = MOST TOXIC = EMETIC, NEPHRO AND OTO Toxicity

47
Q

Group I Biotherapeutics

A

Enzymes and Regulatory Proteins
• Mainly relevant to endocrine & metabolic diseases & hemostasis
• Eg insulin; growth hormone; alglucosidase alpha (Pompe disease); clotting factors viii and ix; fibrinogen

48
Q

FOLFIRI

A

Irinotecan + 5FU/LV

49
Q

NSAID Hypersensitivty

A

Ocular and nasal congestion
Sever bronchospasm
Anaphylaxis.
Variety of skin reactions. (Stevens Johnson Syndrome)

50
Q

Resection?

A
  • Direct correlation between RR and resection rate
  • Tumour progression on ‘pre-operative’ chemotherapy = an independent poor prognostic factor even after potentially curative liver resection
  • Curative strategies should focus on hepatic resection rate as an end-point
51
Q

Nomenclature of -mAb drugs

A

Prefix = Unique for each.

2nd part = Drug Disease Group orginially developed for.

3rd Part = Species the mAb was derived from, the first vowel occurring in the species name.

End = mAb (monoclonal antibody).

52
Q

FOLFOXIRI

A

Better than two.

53
Q

xi

A

Chimeric

54
Q

Cyclophosphamide

A

Alkylating Agent

55
Q

Gemtuzumab Ozogamicin (Mylotarg)

A

Group II b mAb
Targets Anti-CD33 in LYMPHOMA
WITHDRAWN Die to Liver Tox

56
Q

Adjuvant Chemotherapy

A

+20% Benefit in survivability v surgery alone.

57
Q

Bevacizumab

A

Humanized mAb that binds VEGF (ANTI-VEGF)
Colorectal cancer
Long T1/2

S/E
Hypertension 
Albuminuria
GI Perforation (1% risk, mech not fully understood) 
Arterial Thrombotic Events
Impaired Wound Healing

Wound healing; bleeding; liver regeneration

58
Q

Rituximab

A

Chimeric mAb against CD20
Non-Hodgkins lymphoma
Also now RA

59
Q

Entercept

A

TNF receptor–Fc fusion protein
• A dimeric fusion protein between the soluble TNF-α receptor and Fc portion of human IgG1
• Used to treat moderate-severe RA and also severe polyarticular juvenile RA.
• Basically a TNF antagonist
• Very successful drug

60
Q

Catecholamines as biomarker.

A

Mostly Pheochromocytoma

MEN2a and MEN2b
Von Hippel-Lindau syndrome
Neurofribromatosis
Familial paraganglioma

24 hour collection required in acid preservative for the measurement of adrenaline, noradrenaline and dopamine
2/3 collections if transient hypertension. 1 if hypertension.

61
Q

Oxiplatin

A

Platinum Analogues
Reactive complex that cross links guanine units in DNA.
Derivative from Cisplatin
Works by inhibiting DNA synthesis
Accumulative toxicity = Neuropathy (Related to cold. Can result in laryngeal spasm due to nerve hypersensitivity, other examples include hand spasm when reaching into fridge)
Toxicity = Sinusoidal dilatation and vascular injury

62
Q

Predicts Recurrence after resection

A

FONG Score

63
Q

DPD Deficiency

A

Autosomal recessive metabolic disorder
Absent or significantly decreased activity of dihydropyrimidine dehydrogenase

Means that the drug is not broken down and recirculated with high toxicity putting the patient in ICU.

This deficiency is rare. Testing or this deficiency is not routine

64
Q

‘zu’

A

HumanIZED mAb

65
Q

o’

A

Mouse mAb

66
Q

Infliximab

A

Group II mAb that binds to and neutralizes TNF-α

Crohn’s disease and RA

67
Q

Paclitaxel

A

Taxanes

Western Yew Tree OR form Syn Doxetaxel

MOA= Prevent Microtubules DISASSEMBLY.
Therefore arrests cell in Mitosis/G2

Assoc w/ severe hypersenstivity.

68
Q

Li prefix

A

Immune

69
Q

Daunorubicin

A

Anti-Tumour Antibiotic

Isolated from Stropomyces SPP

4x MOA’s

  1. Topomerase II inhibition
  2. High Affinity DNA intercalation
  3. Alteration of Membrane Fluidity
  4. Superoxide free radical damage. (cardiotoxic!)

Activation is by hydrOXYlation – Hence Cardiotoxic.

70
Q

Busulfan

A

Alkylating Agent

71
Q

Alkylating Agent MOA?

A

Alpha Side Chain Metabolically Activated
Reactive Produce binds to DNA
Causes read and replication errors

72
Q

Calcitonin

A

Medullary thyroid carcinoma (MTC)

73
Q

Vinblastine

A 
Vinca Alkaloid
Mainly Lymphoma + Testicular Cancer 
Bind to tubulin, preventing microtubulin formation. 
M-Phase specific. 
Myelosuppressive (BM activity down)
74
Q

Multiple Myeloma

A

Monoclonal Protein in Increase amounts.
intact Igs, Ig fragments and/or monoclonal FLCs

Single Clone of Bcells Causes

  • M proteins in blood and urine
  • Excess light chain production and excretion.
  • Amyloidosis
  • Deregulation of clotting factors, hormones and chemicals

DETECTION
Proteins migrate in the electrical field according to their charge and mass

Alpha proteins – alpha 1 antitrypsin, haptoglobin, alpha 2 macroglobulin, HDL

Beta proteins – transferrin, LDL, C3

Gamma proteins – immunglobulins, fibrogen, CRP

75
Q

Etorocoxib

A

Selective

Long Acting

76
Q

HAMA response

A

mAbs are foreign proteins, resulting in immune recognition and anti-mAb production,

77
Q

Capecitabine

A
  • Pro-drug, oral
  • Converted to 5-FU by thymidine phosphorylase
  • Bioavailability of almost 100%
78
Q

ErbB2 receptor signal pathways

A 
PI3K = Cell Cycle + Survival
MAPK = Proliferation
79
Q

COX1 inhibition S/E

A

Stomach, platelet, kidney

80
Q

Celecoxib

A

CO2 selective

Pyrazole.

81
Q

Ibuprufen

A

Non COX Selective

Propionic acid

82
Q

Ifosfamide

A

Alkylating Agent

83
Q

i’

A

Primate

84
Q

HER Receptors

A 
HER2 = No Ligand
HER3 = No kinase activity

HER2:3 dimers initiate the strongest mitogenic signalling.
HER2:3 dimers can be ligand activated and HER2 can phosphorylate HER3’s intracell cascade. = Multiple signal pathways = increase tumour proliferation.

85
Q

Group II Biotherapeutics

A

Targeted Proteins (The NB’s)
• Further subdivides into
o Group IIa – Interfering with a molecule or protein (preventing ligand binding)
o Group IIb – Delivering other compounds or proteins (antibody drug conjugates, which target antibody expressed by a group of cancerous cells)

86
Q

u’

A

Human

87
Q

Complete response Chemo in CRC w/Liver Mets

A

You must still perform a resection of the affect liver area, since recurrence in the affected tissues is common, possibly due to the augmentation of the immuno-system with chemo.

  • Difficult for the surgeon to resect
  • Radiologic CR does NOT mean pathologic CR
  • Duration of ‘preoperative’ treatment is critical
  • HAI has been shown to be an independent predictor of pCR
88
Q

6 MP (Mercaptopurine–> 6 Thioguanine)

A

Anti-Metabolites (-Purine Anatagonists)
Cell Cycle Specific (S-Phase)
Childhood Leukaemia
Pro Drug (Mercap to Thioguanine)

89
Q

Challenges of Biotherapaeutics?

A

Drug delivery very difficult
Cost (& its ethical implications)
o Biosimilars will help reduce this
Immunogenicity problematic
o e.g hemophilia patients may make antibodies to Factor VIII when it is replaced. Increased humanization now…
Proteins are large molecules with both hydrophilic and hydrophobic character
o Solubility
o Route of administration
o Distribution – entry into cells difficult
o Stability – subject to degradation/ clearance
o Post-translational modification nb for function
PEGylation used to prolong absorption, decrease renal clearance, increase half- life and reduce immunogenicity of many proteins

90
Q

Carcinoembryonic antigen (CEA)

A

200 kDa glycoprotein and plays a role in cell adhesion
Elevated in most advanced adenocarcinomas: colorectal cancer but also tumours of pancreas, breast, lung
Was used for screening CRC but not specific enough now.

Used for monitoring rather than diagnosis
e.g. CA 125 (ovarian), CA 19-9 (pancreatic), CA 15.3 (breast)

91
Q

Sorafenib Pazopanib and sunitinib

A

vEGF inhibtors

92
Q

Human mAb

A

Where the sequence is entirely human, can be generated in a number of ways including immunization of transgenic animals that have a human immune system, repertoire cloning, and other techniques.

93
Q

Breast Cancer mAb’s

A

Trastuzumab
Pertuzumab
T-DMI

94
Q

5-FU (5-Fluorouracil)

A

Anti-Metabolite (Pyramiding Antagonist)
Inhibits synthesis of Thymine (vital for DNA synth)
Acts by irreversibly inhibiting thymidylate synthase
Leucovorin enhanced binding of 5FU to its substrate (TS)
Infusional better than bolus
HDFL

Very Short T1/2
Used widely in Solid Tumours
TOXICITY = Hepatic steatosis

95
Q

Ipilimumab

A

Anti-CTLA-4 Antibody,
Preventing CTLA-4 from binding to B7 and inactivating the cytotoxic t-cell. i.e. Switches off the off switch of CTLs

Metastatic Melanoma
(possibly, RCC, Prostate and Lung)

S/E: Colitis, Hepatits, Hypophysitis.
Treat with: Corticosteroids and Anti-TNF antibody if refractory.

96
Q

Melphalan

A

Alkylating Agent

97
Q

Melanoma mAb’s

A

Ipilimumab

Novolumab

98
Q

Nivolumab

A

Anti-PD1

Anti-PD1 antibodies may be more relevant to unleash an anti-melanoma immune response than anti-CTLA4 antibodies

Oncology (5 decks)

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