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Cancer Pharmacology > Systemic Clinical Cancer Treatment (1) > Flashcards

Systemic Clinical Cancer Treatment (1) Flashcards

1
Q

Give examples of loco-regional therapies

A

Surgery

Radiotherapy

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2
Q

What are systemic medicines?

A

Cancer medicines

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3
Q

Why is systemic cancer therapy important?

A

Most patients have metastasis already at the time of diagnosis
Loco-regional therapies cannot target these

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4
Q

How big does a tumour have to be to be detected clinically?

A

~2cm

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5
Q

How big does a tumour have to be to be treated with radiotherapy?

A

~1cm

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6
Q

What is it called if the tumour is below the clinical detection size?

A

Micrometastatic disease

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7
Q

How many cells are in a 1cm tumour mass?

A

~1 million

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8
Q

How many cells are in a 2cm tumour mass?

A

~1 billion

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9
Q

Name the types of systemic therapies

A

Cytotoxic chemotherapy
Targeted agents
Endocrine therapy
Immunotherapy

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10
Q

What is endocrine therapy?

A

Anti-oestrogen and anti-androgen therapy for hormone driven cancers - breast and prostate

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11
Q

Why is combination therapy advantageous?

A

Decrease the chance of resistance or delays its emergence

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12
Q

What is the issue with combination therapy?

A

Toxicities can be severe

Need to lower dosages

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13
Q

What are the two types of endocrine therapies?

A

Receptor antagonists

Reduce the production of oestrogen and androgen

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14
Q

Name examples of endocrine therapy, receptor antagonists

A

Oestrogen - Tamoxifen

Androgen - Cyproterone

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15
Q

Name examples of endocrine therapy, reducing the production of oestrogen and androgen

A 
Gonadotrophin Releasing hormone analogues (oestrogen and androgen) 
Aromatase inhibitors (oestrogen only)
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16
Q

Advantages of endocrine therapies

A

Relatively few side effects

Well tolerated

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17
Q

Disadvantages of endocrine therapies

A

Can take up to 3 months to have a clinically beneficial effect
Long term side effects:
- osteoporosis
- cardiovascular disease

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18
Q

Why is osteoporosis a side effect?

A

Bone mass is dependent on oestrogen and androgens

19
Q

Who may not benefit from endocrine therapies?

A

People will advanced stage disease who need a fast response

20
Q

What do small molecule drugs end in?

A

‘-nibs’

21
Q

What do monoclonal antibody drugs end in?

A

‘-mabs’

22
Q

Name a targeted drug for renal cell carcinoma and hepatocellular carcinoma and how it works

A

Sunitinib

Anti-angiogenic drugs which target VEGF and VEGFR

23
Q

What are the advantages of targeted drugs?

A

More effective than chemotherapy
Less side effects
Can be used in combination with chemotherapy without increasing toxicity
Can be used in patients who are resistant to chemotherapy

24
Q

Name a targeted drug which can be used in NSCLC patients who are unfit for chemotherapy

A

Erlotinib - targets EGFR

25
Q

Name a targeted drug which is used in combination with chemotherapy

A

Trastuzumab (Herceptin) for HER2+ breast cancer

26
Q

Name a targeted drug which can be used in CRC patients who are resistant to chemotherapy

A

Cetuximab - targets EGFR

27
Q

What is the new molecular classification of cancer?

A

Where cancer can be broken up into molecular subgroups, based on biomarkers, and these molecular subgroups tell you what to target

28
Q

What do tumour cells express on their surface?

A

Neoantigens

29
Q

What are neoantigens important for?

A

Allowing the immune system to prevent early tumours (immune surveillance)

30
Q

What are clinical immunotherapies?

A

Immune checkpoint inhibitors

  • CTLA-4 inhibitors
  • PD-1/ PD-L1 inhibitors
31
Q

Name a CTLA-4 inhibitor and describe it

A

Ipilimumab
Monoclonal antibody
Inhibits CTLA-4 so B7 binds to CD28 (co-stimulatory molecule)

32
Q

Why do tumour cells express Pd-L1 on its surface?

A

To inhibit T cell activation

33
Q

What increases the effectiveness of immune checkpoint therapies?

A

High mutational burden

34
Q

Name a PD-1 inhibitor

A

Pembrolizumab

35
Q

What is the main benefit of immune checkpoint therapy?

A

The response appears to be long term

36
Q

How long to immune therapies take to be effective?

A

~6 months

after see tumour growth in this time

37
Q

What auto-immune toxicities are associated with immune checkpoint therapies?

A

Colitis
Pneumonitis
Endocrinopathies

38
Q

What is the next steps for immune checkpoint therapies?

A

Combination therapies
Biomarkers
New immune checkpoint therapies

39
Q

Why may combining chemotherapies with immune therapies be helpful?

A

The chemotherapy drugs will cause a response early on and this may remove the lag phase in the beginning

40
Q

What kind of biomarkers could be used for immune checkpoint therapies?

A 
Tumour:
- tumour mutation burden 
- PD-L1 immunohistochemistry 
- Microsatellite instability (MSI) - High 
Immune infiltrate in tumour 
- CD8 positive TIL score 
- Immunoscore 
- Immune gene expression signature
41
Q

What is neoadjuvant therapy?

A

Having chemotherapy before surgery

42
Q

What is adjuvant therapy?

A

Having chemotherapy after surgery

43
Q

Who benefits from neoadjuvant and adjuvant therapies?

A

Patients who are MSI-high -ve

Cancer Pharmacology (13 decks)

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