L8 Drug Discovery in Oncology Flashcards

1
Q

What is cancer?

A
  • Cancer is typically caused by genetic lesions that affect genes that promote proliferation in tandem with lesions that interfere with the elimination of cells through apoptosis.
  • Cancer is not a single disease but a wide spectrum of conditions caused by a failure of the controls that normally govern cell proliferation, differentiation and cell survival
  • multi-step process and involves the acquisition of a series of mutations in oncogenes and tumor suppressor genes that cooperate to achieve the fully transformed state.
  • Cancer incidence varies between tissues.
  • Mutagenic agents, including viruses, promote cellular transformation.
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2
Q

What is the objective of targeted therapy?

A

Slide 10
- Improve tumour response to chemo and radiotherapy (often dual therapy)
- Overcome primary/acquired chemo and radioresistance from cancer cells
- Thus protecting patients from recurrence
- Protect patients from/combate metastasis of malignant tumours

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3
Q

What are the differences between targeted therapy and chemotherapy?

A

Slide 11
- Higher drug distribution (Designed to interact with target), Wider therapeutic index (cytostatic vs cytotoxic), Higher selectivity (Specific molecular target)

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4
Q

How do you identify targets for targeted cancer?

A

Slide 12

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5
Q

What are the characteristics of targeted therapy (small mol/mAb)?

A

Slide 13

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6
Q

What causes drug resistance?

A

Slide 16

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7
Q

Which specific protein causes multi-drug resistance?

A

Slide 19, 21, 22, 23, 24

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8
Q

How does the role of cancer stem cells/properties of cancer cell shape treatment method?

A

Slide 25, 26
- CSC are more resistant to treatment and they are capable of regenerating a new cancer
- However, when drugs specifically target CSC, non CSC can dedifferentiate back to CSC and regenerate another tumour
- Skipper Schabel model - all cancerous cells need to be killed as even 1 cell can regenerate another tumour (but must spare the host of the toxicity)

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9
Q

Using the example of BCR-Abl, explain drug resistance with respect to Gleevac.

A

Slide 27, 28, 29, 30

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10
Q

How do you screen for resistant mutant forms of BCR-Abl?

A

Slide 31, 32, 33

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11
Q

What are some drugs to tackle the mutant forms of BCR-Abl?

A

Slide 34, 35

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12
Q

Why does the immune system not recognise cancer cells/kill cancer cells

A

Slide 36
- Immune cells does not recognise tumour antigen as foreign -> Lack of T-cell costimulatory mechanism allows cancer cell to evade immune system

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13
Q

Properties of tumour antigens

A

Slide 37

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14
Q

What are the different types of tumour antigens T-cells recognise?

A

Slide 38

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15
Q

How does T cells kill tumour cells?

A

Slide 39
- Antigen presenting cells (dendritic cells) ingest/phagocytose tumour cells
- APC presents CD40 on its surface
- CD4+ T helper lymphocyte with CD40L recognises CD40 and is activated
- Releases cytokines and recruits CD8+ T cell
- Causes the differentiation of tumour specific CD8+ T cells (memory)
- Tumour specific CD8+ cytotoxic T lymphocyte recognises tumour cell
- Leading to killing of tumour cell

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16
Q

What are the different approaches to cancer immunotherapy?

A

Slide 40

17
Q

How does cancer vaccine work?

A

Slide 41, 42

18
Q

How does immunization with whole tumour cells work?

A

Slide 43
Whole cell tumour probs better bc provide a source of all potential antigens, eliminating the need to identify the most optimal antigen to target in a particular type of cancer. Multiple tumour antigens can be targeted simultaneously, generating an immune response to various tumour antigens.
- May increase risk of introducing of possible tumour source compared to peptides

19
Q

How does therapy with subunit vaccines work?

A

Slide 44

20
Q

What is passive immunotherapy?

A

Slide 45
- Monoclonal Ab that targets specific antigens eg CD20
- CD20, CD30, CD52, erbB2
- Bifunctional Ab (CD3 and CD19)

21
Q

How is adoptive T cell performed?

A

Slide 46

22
Q

How is checkpoint blockers used for therapy?

A

Slide 47

23
Q

What is the latest immunotherapy?

A

CAR T cell therapy
Slide 48 + Cancer notes

24
Q

How do you analyse which treatment is better based on immunotherapy?

A
  • Blood samples
  • Cytokines are only produced by T cells
  • Taking the blood samples, incubate with tumour cells and measure the cytokine response