cancer models Flashcards

1
Q

step wise model of cancer transformation

A

Mutation 1 - removes a negative regulator of cell cycle

Mutation 2 - activates a positive regulator of cell cycle

Mutation 3 - inhibits cell death

Additive effects of TME

Transformed cancer cells

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2
Q

what should a good cancer model have

A
  • relevance to human biology
  • predictive accuracy: do treatments translate
  • scalability: how many conditions can you test
  • reproducibility - should be easily reporducible
  • integrates heterogenity - how complex is the system
  • mechanic insight - how reductionist can it be
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3
Q

cell lines

A

cultured cancer cells, taken from a patient and grown in a lab

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4
Q

cell lines pros

A
  • Continuous and unlimited supply of cells
  • Consistent genetic and phenotype chatacteristics
  • Ease of handling
  • Can be modified easily and excellent Techniques to study molecular interactions
  • Ability to maintain cells under controlled conditions
  • Cost effectiveness
  • Automated process
    Can be grown in different conditions
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5
Q

cell lines negatives

A
  • Risk of genetic drift and mutation
  • Artificial environment
  • Possible contamination issues
  • Lose relevant in vivo characteristics
  • Ethical concerns
  • Homogenous cultures
  • No gradients or 3D or TME
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6
Q

organoids

A

3D cultures of cells that mimic the structure and function of an organ

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7
Q

organoids pros

A
  • continuous and unlimited supply of cells
  • consistent genetic characteristics
  • ease of handling
  • can be modified easily
  • ability to maintain cells under controlled conditions
  • cost effectiveness
  • gradients and heterogenous
    -can be grown in different conditions
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8
Q

organoids negs

A

– risk of genetic drift and mutation
- artificial environment
- possible contamination issues
- lose relevant in vivo characteristics
- ethical concerns
- homogenous cultures
- less reproducible
- harder to study mechanisms

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9
Q

xenografts

A

use cells (cell lines) from patients implanted into a mouse

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10
Q

xenografts positives

A
  • closer in vivo tumour biology
  • study more tumour host interactions
  • better drug discovery and testing
  • lots of cancer cell line variants
  • can study metastasis
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11
Q

xenografts negatives

A
  • limited generalisability to humans
  • no host immune system
  • difference in TME
  • ethical concerns
  • limited reproducibility between animal models
  • uses homogenous cell lines
  • expensive
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12
Q

patient derived xenografts

A

use cells from a patients tumour that are implanted into a mouse, with the cells being maintained by serial passage in the mouse

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13
Q

tumour induced mouse models

A

genetically engineered mice models

  • genetic models: tissue modified to express oncogenes
  • spontaneous models: uses cancer causing agents to develop cancers
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14
Q

tumour induced mouse pros

A
  • Close in vivo tumour biology
  • Study tumour host interactions
  • Potential in drug discovery and testing
  • Controlled changes to genetic background
  • Ability to study tumour progression and metastasis
  • Develops naturally time and TME
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15
Q

tumour-induced mouse negs

A
  • not scalable
  • time takes months and months
  • difference in TME
  • ethical concerns
  • limited reproducibility between different animal models
  • high cost and technical expertise required
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16
Q

zebrafish models

A

use Zebrafish, which can be genetically modified to develop tumours

17
Q

zebra fish pros

A
  • rapid development
  • high throughput screening
  • transparent embryos for visualising tumour growth
  • crossing models rapid
  • inexpensive
    -conservation of gene function across species
18
Q

zabra fish negs

A
  • differences in TME
  • ethical concerns
  • limited reproducibility between different animal models
  • technical expertise required
  • limited understanding of fish tumours and immune system
  • few examples of drug discoveries
19
Q

PDX pros

A
  • closes representation of humour tumour
  • patient specific tumour - host interactions
  • personalised medicine
  • availability of human tumour specimens
  • ability to test multiple drugs and treatments
  • drug response is the most predictive
20
Q

PDX negs

A
  • patient specific
  • no host immune system
  • differences in tumour microenvironment
  • ethical concerns
  • high cost and technical expertise required
  • slow and limited material
  • limited mechanistic insight
21
Q

omics based models

A

use large scale data sets of different omics data, such as genomics, transcriptomics, proteomics and metabalomics, to understand the underlying mechanisms of cancer development, progression and drug resistance.

22
Q

omics pros

A
  • high throughput analysis
  • ability to study complex biological systems
  • integration of multiple layers of information
  • increased data accuracy
  • ease of data generation
  • non bias
  • ethical
23
Q

omics negs

A
  • limited functional analysis
  • basically no mechanical insight
  • large amounts of sample material
  • problem of data integration and interpretation
  • limited understanding of the causal relationship between changes in molecules and biological processes
  • can not stand alone
  • expensive