Brainscape's Knowledge GenomeTM

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


See full index

Stage 4 Oncology > Targeting cell proliferation and survival > Flashcards

Targeting cell proliferation and survival Flashcards

1
Q

Three main hallmarks of cancer ?

A

Evading TGSs (tumor growth suppressors)

Resisting cell death

Sustaining proliferative signalling

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

Steps of the Cell Cycle Regulation

A

All cells must undergo replication!

  1. Unreplicated DNA
  2. Spindle assembly (mitosis)
  3. Chromosome segregation (mitosis)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Chemotherapy action

A

Works at different stages to stop an overactive cell cycle

  • Inhibits cell growth (using growth factor proteins)
  • Inhibits DNA duplication (DNA interactive agents)
  • Inhibits cell division (Replicative machinery)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Which cytotoxic agents are cell cycle specific ?

A

Antimetabolites

Vinca alkaloids

Taxanes

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

Which cytotoxic agents are non-phase specific ?

A

Anthracyclines

Alkylating agents

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

Mechanism of action for MTX?

A 
Inhibits dihydrofolate reduction
Blocks TMP (trimethoprim) and purine synthesis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Mechanism of action for 5-flouracil? 5FU

A

Inhibits TMP (trimethoprim) synthesis

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

Mechanism of action for paclitaxel?

A

Inhibits seperation of microtubules in anaphase of mitosis

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

What are Cyclin-dependent Kinase Inhibitors (CDKIs)?

A

Family of enzymes involved in the cell cycle regulation

Consist of Ser and Thy kinases

Involved in phosphorylation using ATP

CDKIs consist of purine anlalogues that may bind and block the ATP site on the enzyme

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

Describe action of Palbociclib (Ibrance®) by Pfizer (Approved Nov 2017 by NICE)

A
  • Inhibits CDK4-cyclin binding
    (Ineffective against CDK1, CDK2, CDK5)
  • Effective against ER +ve / HER2 -ve advanced breast cancer in conjunction with hormones
  • Median PFS 9.2 months
  • DLT (dose limiting toxicities): neutropenia, fatigue, thrombocytopenia
  • One cycle £2,950 for pack of 21 capsules (1CAPOD)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What does Azacytidine incorporate into ?

A

RNA

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

What does Decitabine incorporate into ?

A

DNA

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

What position does DNA methylation occur for epigenetics?

A

5-position of cytosine by DNA methyltransferases (DNMTs) in CpG islands
- This prevents gene transcription

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

In relation to epigenetics, what do 5-Azacitidine and 5-aza-2’-deoxycitidine (Decitabine) do?

A

Restore NORMAL methylation patterns in many haematological malignancies

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

What is the mechanism for silencing tumour suppressing genees (TSGs)?

A

Histone deacetylation (HDAC)

E.g. ZOLINZA® (vorinostat) for cutaneous T-cell lymphoma

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

Define: Telomere

A

The structure located at the end of the chromosome

They have control over the cell division limit

Cancer cells often have longer telomeres that last through more rounds of DNA replication, allowing for the cells to divide more - Overexpression of telomerase enzyme makes telomeres longer in cancer cella :/

17
Q

How do we ENABLE REPLICATIVE IMMORTALITY (the 4th Hallmark of cancer)
NB. It means that cancer cells can replicate without limit

A

Use of telomeres

18
Q

What do Anti-Mitotic Agents do? Their role.

A
  • Promote microtubule polymerisation
  • Inhibit depolymerisation
  • Stabilisation of microtubules

and arrests cells in mitosis

19
Q

What is anti-mitotic agents dependent on to work?

A

GTP

20
Q

What is a cyclin dependent kinase inhibitor (CDKI)

A

Family of enxymes involved in the cell cycle
Involved in phosphorylation using ATP
Ser and Thr kinases

21
Q

What is the basis for design of cyclin dependent kinase inhibitors?

A

Purine analogues that might bind and block the ATP site on the enzyme (allowing for space to accommodate further elaboration)
E.g. NU2058

22
Q

What are telomeres composed of?

A

Tandem repeats of GC-rich DNA (up to 10kbp in humans)

23
Q

What is the function/role of telomeres?

A

Protect chromosome ends from recombination, fusion, or degradation by nuclease

24
Q

What type of enzyme is Telomerase?

A
  • Type of reverse transcriptase

- Protein-RNA complex that carries the RNA template for synthesising the repeated G-rich telomere

25
Q

What is the relationship between cancer and telomerase?

A

Presence of telomerase in cancer cells allows them to maintain telomere length

26
Q

What do telomeres protect chromosome ends from?

A

Protect against recombination, fusion and/or degradation by nuclease

27
Q

What is telomerase enzyme unique for?

A

Carrying its own RNA template at ALL TIMES (to synthesise G-rich telomeres)

28
Q

What is the normal level of telomerase and why?

A

Low levels

Because as telomeres shorten as cells divide

29
Q

How do we enable replicative immortality? (Hallmark of cancer)

A

Use of telomeres….

30
Q

Describe the intrinsic apoptosis pathway

A
  • Triggered in response to DNA damage
  • Activated by anticancer therapies via p53
  1. p53 activates the pathway through protiens of the Bcl-family e.g. BAX, BAK
  2. BAX causes releases Cytochrome C from mitochondria
  3. BAX and adaptor APAF1 activates the initiator capsase 9
  4. Capsase 9 activates capsases 3, 6, 7 causing apoptosis (by destroying critical cell components)
31
Q

How does p53 activate the intrinsic apoptosis pathway?

A

Activates it through transcriptional upregulation of pro-apoptotic members of the Bcl-family of proteins e.g. BAX, BAK

32
Q

Extrinsic vs Intrinsic apoptosis pathway

A

EXTRINSIC Induces apoptosis INDEPENDENT OF p53 and mitochondria
INTRINSIC induces apoptosis via p53 and uses mitcohondria

33
Q

Describe the extrinsic apoptosis pathway

A
  1. Specific pro-apoptotic ligands e.g. Apo2L/TRIAL activate pro-apoptotic receptors e.g. DR4, DR5
  2. Activation of receptors by the ligan leads to rapid assembly of Death Inducing Signalling Complex (DISC) & recruitment of initiator capsases 8 + 10 via the Fas-associated death domain (FADD)
  3. Caspases 8 + 10 activate capsases 3, 6 and 7 which leads to apoptosis
34
Q

Development of which agents to induce apoptosis? (Two items)

A
  1. Inducers of apoptosis

2. Inhibitors of anti-apoptotic proteins

35
Q

Mechanism of action of Vincristine? (Vinca alkaloid)

A

Bind to microtubules and inhibit polymerisation to destabilise them… cannot perform metaphase

Stage 4 Oncology (10 decks)

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