Biological Basis Of Treatment Flashcards

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1
Q

What is implantation of tumours? Where are implants commonly found?

A

Mechanical spread of detached clumps of tumour cells, commonly found in peritoneum, ureters and CSF

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2
Q

List all the treatment options of cancer

A
Surgery
Radiotherapy
Chemotherapy
Hormones
Biologically targeted therapy
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3
Q

What are the different forms of chemotherapy?

A

Primary treatment
Adjuvant - after an operation
Neoadjuvant
Palliative

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4
Q

What is neoadjuvant therapy?

A

Primary treatment with chemotherapy for patients with a localised tumour. Can be used to assess biological responsiveness of tumours and before surgery to reduce tumour size

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5
Q

Why must chemo be administered in pulses?

A

Chemo depletes bone marrow as well

Bone marrow cells can recover to a higher level than cancer cells between doses so needs to be given in pulses

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6
Q

When would chemotherapy be given continuously?

A

If the patient is to have a bone marrow transplant

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7
Q

What are the different types of chemotherapies and what are their sites of action?

A

Antimetabolites stop DNA synthesis
Alkylating agents bind to DNA and fix it so it cannot be unwound
Intercalating agents affect DNA transcription and duplication
Spindle poisons stop mitosis

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8
Q

What do platinum compounds do?

A

Form platinated inter- and intra-strand adducts leading to inhibition of DNA synthesis

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9
Q

What is the overall aim of chemotherapy?

A

To cause DNA damage so that apoptosis is induced

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10
Q

What do topoisomerase-1 inhibitors do?

A

Inhibit topoisomerase-1
Topoisomerase-1 cleaves a strand of DNA transiently so that the other strand when tightly wound up in supercoiling can be unwound. The strand is then religated and can have normal replication
Inhibits the rejoining of strands causing single and double strand breaks - apoptosis

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11
Q

What does methotrexate do?

A

Targets the folate cycle which is needed to produce purines for DNA synthesis

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12
Q

What does 5-fluorouracil do?

A

Inhibits thymidilate synthase which is required for pyrimidine and purine synthesis and the folate cycle

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13
Q

Why are microtubule dynamics critical for mitosis?

A

They polymerise to attach to the chromosomes

They depolymerise to move sister chromatids away from the metaphase plate during anaphase

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14
Q

What do microtubule binding agents do?

A

Disrupt microtubule dynamics

  • inhibit polymerisation
  • stimulate polymerisation and prevent depolymerisation, so that chromatids cannot be pulled apart
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15
Q

What is the aim of combination therapy?

A

Increased efficacy by

-activity - different mechanisms of action

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16
Q

Problems with combination therapy?

A

Different mechanisms of action can cause different mechanisms of resistance
Need to consider side effects - safety

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17
Q

List some types of endocrine therapies for breast cancer

A

Anti-oestrogens eg tamoxifen
Aromatase inhibitors
Progesterones eg megestrol
LHRH agonists eg goserelin

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18
Q

How do aromatase inhibitors work?

A

Aromatase converts compounds to oestrogens and is located in ovaries and fat
Have less oestrogen if aromatase is inhibited

19
Q

What are some current endocrine therapies for prostate cancer?

A
LHRH antagonists eg goserelin
Anti-androgens eg flutamide 
Oestrogen 
Castration 
CYP17A1 inhibitor
20
Q

What are some side effects of anti-androgens?

A

Less facial hair
Gynaecomastia
Loss of libido

21
Q

How does a CYP17A1 inhibitor work?

A

This enzyme is crucial for conversion of pregnenolone and progesterone to testosterone, therefore have less testosterone production

22
Q

What differences between cancer cells and normal cells can be exploited by biologically targeted therapy?

A

Cancer cells

  • loss of contact inhibition
  • increase in growth factor secretion
  • increase in oncogene expression
  • loss of tumour suppressor genes

Normal cells

  • oncogene expression rare
  • intermittent or coordinated growth factor secretion
  • presence of tumour suppressor genes
23
Q

What mutation is seen in myeloid leukaemia?

A

Philadelphia chromosome - a translocation between 9 and 22

  • leads to transcription of a protein and leukaemic transformation
  • activation of oncogene
24
Q

What is imatinib?

A

A Bcr-Abl tyrosine kinase inhibitor

25
Q

What happens if tyrosine kinase is switched on permanently?

A

Can cause unregulated cell growth

Tyrosine kinase is an enzyme which can transfer a phosphate group from ATP to a protein in a cell

26
Q

What do all the therapies ending in ‘nib’ do?

A

Inhibit tyrosine kinase

27
Q

What are signal transduction pathways?

A

Biochemical pathways that communicate to the nucleus

28
Q

What is Herceptin?

A

A recombinant humanised IgG1 monoclonal antibody against human epidural growth factor receptor 2 (HER-2)

29
Q

How does Herceptin work?

A

Binds to HER2+ cells and flags them for immune destruction

Blocks downstream HER2 signalling to inhibit proliferation of cells

30
Q

What is high expression of EGFR in cancer cells associated with?

A
Invasion
Metastasis
Late-stage disease
Chemotherapy resistance 
Hormone therapy resistance 
Bad prognosis
31
Q

What does erbitux do?

A

Targets EGFR - it is an IgG1 monoclonal antibody

Inhibits EGFRs, altering the signalling cascade leading to multiple effects

32
Q

Side effect of erbitux?

A

Can cause bad acne

33
Q

What is panitumumab?

A

An anti-EGFR monoclonal antibody

34
Q

What is panitumumab used for?

A

Commonly used in EGFR-expressing metastasis colon cancer with wild type K-Ras
However being phased out due to cost

35
Q

How does VEGF promote angiogenesis?

A

Induces endothelial cells to invade collagen gels and proliferate to form capillary-like structures to form new blood vessels

36
Q

Give the steps of angiogenesis

A

Endothelial cells migrate into the perivascular space towards angiogenic stimuli
They proliferate and adhere to create a lumen
Blood vessel spouts fuse to build new circulatory systems

37
Q

List some therapies that target VEGF

A

Bevacizumab

Abflibercept

38
Q

How does bevacizumab work?

A

It is a VEGF antibody

Binds to it, preventing it from interacting with its receptor

39
Q

How does Abflibercept work?

A

An antibody which binds to VEGF so that VEGF cannot bind to its receptor

40
Q

What are the different ways that rumours can spread?

A

Local
Lymphatic
Blood
Implantation

41
Q

Give an example of an intercalating agent

A

Topoisomerase-1 inhibitor

42
Q

Give an example of an alkylating agent and how it works

A

Cyclophosphamide

Adds an alkyl group to DNA causing the two strands to cross-link. The strands cannot be separated and replicated

43
Q

Give an example of an anti-metabolite

A

Methotrexate

5-flurouracil