Cancer Flashcards
What are the types of treatments used in cancer?
Surgery
Radio therapy
Targeted therapy
Chemotherapy
What are the types of targeted therapies?
RNA targeted
Tyrosine kinase receptor targeted
Inflammation targeted
Describe the types of RNA targeted therapy?
ANTISENSE
MOA:
1. DNA converted to mRNA
2. Antisense Oligonucleotide complementary to a section on mRNA
3. Binds and inhibits mRNA conversion to a protein
MICRO-RNA MOA: 1. mi-RNA= short segments of dsRNA 2. Recognition by RISC enzyme complex 3. Becomes siRNA (small inhibitory) 4. siRNA binds complementary mRNA 5. RISC cleaves mRNA= Degradation= no gene product synthesis
What is signal transduction?
Transmittance of signal through a cell, from a cells exterior to interior.
Describe the steps in signal transduction?
- Ligand/protein bind to Receptor with high affinity
- Conformational receptor change
- Extracellular signals converted to intracellular signals
Give an example of a signal transduction pathway?
MAPK signalling pathway
Describe the structure of tyrosine kinase receptor involved in MAPK signalling pathway?
Extracellular domain= ligand binding site
Transmembrane domain= alpha helix
Cytosol domain= TKR activity
Intracellular domain= site of phosphorylation of Tyr residues on proteins
Describe the steps in MAPK signalling pathway?
- Ligands bind to adjacent tyrosine kinase receptors
- Receptors associate and dimerise
- Tyrosine kinase domains become activated
- Tyrosine residue is phosphorylated in the intracellular domain
- Phosphorylated group act as binding site for intracellular signalling protein
- Leads to cascade and activation of downstream signalling pathways
What cancer drugs target kinases and signal transduction pathway?
Bevacizumab Trastuzumab Herceptin Imatinib mesylate Gefitinib Tamoxifen Dabrafenib Vemurafenib
What is the use and mode of action of Bevacizumab?
Colorectal cancer use
MOA: Disrupts ligand receptor binding
1. Bind to tumour protein VEGF
2. Inhibits VEGF binding to its receptors and blocks signal initiation
3. Inhibits cell proliferation and stops new blood vessels forming
What is the use and mode of action of Trastuzumab and Herceptin?
Over expressed HER2 tumours MOA: Disrupts ligand receptor binding 1. Binds to EGF 2. Prevents HER 2 receptor and EGF binding 3. Blocks signal transduction
What is the use and mode of action of Imatinib mesylate?
Chronic myeloid leukemia
Acute lymphoblastic leukemia
Intestinal stromal tumours
MOA: inhibits phosphorylation and ATP binding
1. Binds to BCR/ABL fusion protein
2. prevents substrate phosphorylation
3. Inhibits signalling so no proliferation or survival
What is the use and mode of action of Gefitinib?
Cancer/tumour with high EGFR expression, lung cancer
MOA: inhibits phosphorylation and ATP binding
1. Binds to EGFR-tyrosine kinase domain
2. Stops ATP binding
3. Inhibits downstream signalling cascade, phosphorylation and signalling
What is the use and mode of action of Tamoxifen?
Breast cancer
MOA: inhibits oestrogen receptor interaction
1. Competitively binds to oestrogen receptor
2. Inhibits oestrogen regulated gene expression
What is the use and mode of action of Dabrafenib and Vemurafenib?
Melanoma
MOA: inhibits MAPK signalling pathway
1. Binds to B-RAF protein
2. Prevents ATP binding and phosphorylation
3. No cell proliferation of B-RAF gene mutation containing tumours
What test is needed for Trastuzumab treatment?
HER 2 expression test on tumour biopsy
What test is needed for Dabrafenib and Vemurafenib treatment?
B-RAF gene mutation diagnostic test
What ways can resistance develop to trastuzumab?
- HER 2 constitutive activation
- EGFR compensation- using EGFR family pathway for alternative cell signalling like over expression of TGF alpha
- Mutation in MAPK/ERK pathway
- Mutation of HER 2
- Phosphotase mutations
- Alternative cell signalling using HER 1
- Intracellular signalling changes
What drugs inhibit pro tumour inflammation?
MAPK inhibitor
Signal inhibitors
What drugs promote anti-tumour inflammation by inhibiting immune checkpoints?
Ipilimumab
Nivolumab
What are the 2 immune checkpoints targeted in anti-tumour inflammation?
CTLA4
PD1/PDL1
What type of drug is Ipilimumab and its MOA?
Anti CTLA4 monoclonal antibody
MOA:
1. Binds to CTLA4 on activated t cells
2. Enhances anti-tumour t cell response
What type of drug is Nivolumab and its MOA?
Anti PD1/PDL1 monoclonal antibody MOA: 1. Binds to PD1 on dendritic and macrophage cell surface 2. Prevents PD1 and PDL1 interaction 3. Activates t cell anti-tumour response
What drugs are used in chemotherapy treatment?
Intercalating agents Alkylating agents Vincrisitine and Vinblastine Topoisomerase II inhibitor Metal complexes Anti metabolites Taxol
AVITMAT
