Signalling pathways in cancer

  1. understand principles of cell signalling

  2. describe using examples how cell signalling is disrupted in cancer

  3. understand methods used to analyse signalling pathways in cancer research

  4. describe using examples how cell signalling pathways are targeted therapeutically

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2

cell signalling controls all the hallmarks of cancer

P13K signalling

Ras signalling

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Profiling methods

DNA

  • measure copy number changes, mutations and translocation

  • sequencing: measures copy number changes, mutations, translocations, single cell sequence and spatial genomics

  • CRISPR screening: measures gene editing technology, genome wide knock out screen, genes essential to cancer survival

RNA

  • measure gene expression changes, mutations and fusion genes

  • RNA sequencing: measures gene expression changes, mutations, fusion genes, single cell and spatial

Protein

  • measure protein levels and modification

  • Immunohistochemistry: measures protein expression, modifications and localisations

  • Mass spectrometry: for identification and quantification, measures modifications and localisation

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Targeted therapies on the P13K pathway

Mechanisms of resistance

  • inc drug efflux from tumour cells → drug transporters

  • genetic events → treatment with herceptin ineffective if downstream mutations in PI3K pathway or mutations in target protein

  • alternative signalling