anti cancer agent Flashcards

1
Q

3 main approaches to eliminate cancer:
the role of these depends on — and —

A
  1. Surgical excision (local)
  2. Radiotherapy (local/regional)
  3. Chemotherapy (systemic/targeted) - Chemotherapy - increasingly used in combination
    with surgery or radiation.
    type n stage of development
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2
Q

in chemo:
— inhibit the proliferation of
dividing cells , but kill normal, rapidly proliferating cells also, e.g. bone marrow, GI mucosa, etc

A

cytotoxic drugs

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3
Q

classes of cytotoxic drugs:

A
  1. Antimetabolites
  2. Alkylating agents
  3. Cytotoxic antibiotics
  4. Plant alkaloids/microtubule inhibitors
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4
Q

1- antimatobilites;
* Structurally related to endogenous
compounds involved in —
* Act by — , — or — metabolic pathways in the biosynthesis of
DNA/RNA
examples:
(A). Folate antagonists (FA)
(B). Nucleic acid synthesis inhibitors

A

nucleic acids ( dna , rna ) synthesis
competition, block or subvert

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5
Q

a. folate antagonist FA
folate metabolism by which folate is essential for synthesis of —- and — which are both essential for — and —

A

purine nucleotides (Guanine & Adenine) and thymidylate
both essential for DNA synthesis and cell division
( folate → dihydrofolate (DHF) → tetrahydrofolate(THF)
↔ methylene-THF → methyl-THF → purine biosynthesis)

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6
Q

— is the most common widely used FA drug
* Acts by inhibiting the metabolism of –
* Inhibits — aka the enzyme which converts folates to tetrahydrofolate
* Affinity of MTX for DHFR is about — that of folate for DHFR
* Maximal effects are — specific

A

Methotrexate (MTX)
folic acid
dihydrofolate reductase (DHFR)
one thousand
s phase

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7
Q

b. Nucleic Acid Synthesis Inhibitors:
* — of purines/pyrimidines
– Inhibit enzymes either — or after — of a further false compound
– Form a — or — which is unable or slower to replicate due to extra binding groups
* — analogues: 6-thioguanine, 6-mercaptopurine
* —- analogues: 5-fluorouracil (5-FU),capecitabine, cytarabine (ara-C)

A

analogues
directly or after formation
false rna or dna
purine
pyrimidine

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8
Q

Widely used, particularly for colorectal cancer —

A

Fluorouracil (5-FU)

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9
Q
  • 5-FU exerts its anticancer effects through:
  • inhibition of —
  • incorporation of its metabolites into –
  • 5-FU is converted to several active metabolites including —-
  • 5FU metabolised extensively in — , —
  • 5FU prodrugs developed for – administration as — activated by cascade of 3 enzymes into 5FU
A

thymidylate synthase (TS)
rna n dna
Fluoro-deoxyuridine monophosphate (FdUMP)
gut n liver
oral
Capecitabine
( check slide 16 pls)

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10
Q
  1. alkylating agents :
    Form —with DNA thereby inhibiting — during — and interfering with —
    * Contain — groups (CnH2n+1) which have the property of forming covalent bonds with — in the cell
    * Form — bond on — residues on same or adjacent strands
A

covenant bonds
dna synthesis
s phase
transcription
alkyl
nucleic acid
irreversible
guanin
( check slide 18 )

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11
Q
  • Cause both intra and inter chain
    linking
  • Main action occurs during
    replication when some parts of DNA
    are unpaired and therefore more
    susceptible to –
A

alkylation

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12
Q

alkylating agent examples:
1- —- derivatives of mustard gas ( WW 1 , II )
- examples : Cyclophosphamide & ifosfamide
- forms —-
- is a — activated in — by —
2- —- as Carmustine [BCNU (bis-chloronitrosourea)]
– Causes alkylation of DNA and form – adducts with proteins
– Can pass — used in the treatment of several types of brain tumours, myelomas and Hodgkin’s lymphoma
3- —- as cisplatin which is a MOA analogue to alkylating agent )
* — complexes react in vivo, binding to and causing — of DNA which ultimately triggers —
* Revolutionised treatment of solid tumours of testes & ovary
* BUT seriously nephrotoxic, peripheral sensory neuropathy, resistance a problem.
* — and — (derivatives) - vastly reduced side-effects

A

nitrogen mustards
bifunctional dna adducts
prodrugs
liver
CYP450s
nitrosoureas
carbamoyl
BBB
alkylating-like
platinum
crosslinling
apoptosis
carboplatin n oxaliplatin

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13
Q
  1. cytotoxic antibiotics:
    * Substances of — origin which prevent mammalian cell division
    * — molecules which interpose themselves between the coils of DNA strands ( aka — ) and cause inhibition of —- biosynthesis
A

microbial
flat
intercalation
macromolecular

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14
Q

Anthracyclines as — are examples of –

A

doxorubicin
cytotoxic antibiotics

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15
Q

in cytotoxic antibiotics:
* Interacts with DNA by — and prevents correct — and exposure of DNA by stabilising — complex.
* Topoisomerase II relaxes supercoils in DNA for transcription.
* Used to treat — , — and — tumours.
* Adverse effect: —
− Produces — which are normally inactivated by:
1. Catalase ( – concentration in heart)
2. Glutathione peroxidase (inhibited by— )

A

intercalation
uncoiling
DNA- topoisomerase II
leukaemia lymphoma n solid tumours
cumulative cardiac toxicity
02 radicals
low
doxorubicin

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16
Q

dna topoiosmerases:
* Manage the — state of DNA in a cell, due to the double helical nature of DNA
* Create — in DNA, thereby allowing the DNA to ‘ – ’ around the helical axis and releasing torsional strain within the area before – the break.
* Two classes of this enzyme:
– topoisomerase I (topo I) functions by breaking just — DNA
– topoisomerase II (topo II) results in a —

A

topological
temporary strap breaks
swivel
resealing
one strand
double;e strand break

17
Q

A. Vinca alkaloids
B. Taxanes
* Of plant origin
* Act on tubulin/microtubule dynamics
are:

A

Plant Alkaloids/Microtubule Inhibitors

18
Q

Vinca alkaloids is a —
* —- : vincristine and vinblastine
* Act by binding to – and inhibiting its — into microtubules
* Prevent – formation and cause arrest at — during mitosis

A

plant alkaloids
spindle poisons
tublin
polymerisation
spindle
metaphase

19
Q

taxanes are —
* — : derivative of yew tree bark
* — : semi-synthetic analogue of
paclitaxel
* Interferes with — by promoting formation of – and preventing— of formed microtubules during–

A

plant alkaloids
Paclitaxel (Taxol)
docetaxel
mitosis
intracellular microtubu;es
disassembly
anaphase

20
Q
  • — most common cause of failed
    therapy
  • Drug treatment itself is a strong –
  • Resistance to cytotoxic drugs may be:
    – —: present when the drug is first given
    – — : developed during treatment with the drug
A

resistance
selective pressure
primary
acquired

21
Q
  • Acquired resistance may be due either to — of the tumour cells or to –
  • Leads to emergence of cells which are less affected or unaffected by the drug
  • — over the sensitive cells
A

adaptation
mutation
selective advantage

22
Q

mechanims of drug resistance:
1. — in amount of drug taken up by cell (e.g. — )
2. Insufficient — of drug ( – not
converted to — metabolite FdUMP* which inhibits — synthase)
3. — concentration of target enzyme (methotrexate: increased dihydrofolate reductase)
4. Increased — of alternative metabolic pathways (— )
5. – of drug induced lesion ( —
agents)

A

decreased
methotrexate
activation
FFU
active
thymidylate
increased
ultilization
repair
antimetabolites
alkhating agents

23
Q

multi drug resistance MDR:
* Exhibit — resistance to many structurally — anticancer drugs (e.g. anthracyclines, taxanes, vinca alkaloids).
* MDR results from — of drug transporters : - ATP-binding cassette (ABC) transporter proteins
* P-glycoprotein (coded for by the mdr-1 gene)

  • Mechanism of action:
    – – accumulation of drugs in cells due to the increased — of a cell surface, energy-dependent, drug transport protein, termed P-
    glycoprotein
    elevated expression
    decreased
    expression
A

simultaneous
dissimilar
increased expression
decreased
increased expression

24
Q

Schematic of P-glycoprotein Drug Transport Molecule
* Membrane transporter that
acts as a —
* — is used to drive the efflux
process
* — role thought to be the
protection of cells against environmental oxins

A

drug efflux pump
atp
physiological
( check slide 33,36)

25
Q

summary of cytotixc drugs:
1. —-
A. Folate antagonists e.g. methotrexate
B. Nucleic acid synthesis inhibitors
– Purine analogues: 6-thioguanine, 6-mercaptopurine
– Pyrimidine analogues: 5-fluorouracil (5-FU), capecitabine, cytarabine (ara-C)

  1. A. Nitrogen mustards cyclophosphamide & ifosfamide
    B. Nitrosoureas e.g. carmustine
    C. Alkylating-like: cisplatin
  2. A. Anthracyclines e.g.doxorubicin
  3. A. Vinca alkaloids e.g. vincristine and vinblastine
    B. Taxanes e.g. paclitaxel and docetaxel
A

antimetabolites
alkylating agents
cytotoxic antbiotcs
Plant alkaloids/microtubule inhibitors