Targeted Cancer Therapy Flashcards
Targeted therapy
Treatment that targets specific molecules driving cancer growth and progression
What is adjuvant targeted therapy
Targeted therapy in combo with surgery/chemo/radio
Why do targeted therapies have less adverse reactions than other treatments
Less likely to affect molecules involved in other functions and healthy tissues
What can biomarkers from molecular profiling be used to assess
Prognosis
Diagnosis
Predict Drug sensitivity/resistance
Predict adverse effects
What is used to individualise treatment plans to specific mutations and cancers
Molecular signatures
Advantages of treatments targeted to individual patients
Improve diagnosis
Decr side effects
Decr use of ineffective drugs
Incr survival
Incr quality of life
Decr costs
Where are the best targets for targeted therapy found
In cancer cells but not in normal cells
What happens after a growth factor binds to a tyrosine kinase receptor
Receptor dimerises and kinase activated
What is the most important tyrosine kinase receptor involved in cancer
HER2
What is the most important oncogenic driver
MAPK pathway
How do targeted therapies targeting growth factors or tyrosine kinase receptors treat cancers
Inactivate MAPK and PI3 pathways decreasing cell growth, proliferation, and angiogenesis
What are the main targets of targeted therapies
Receptors on plasma membrane
Kinase activity within cells
RAS RAF - kinases
2 main types of targeted therapy
Antibodies
Small molecule kinase inhibitors
Why do antibodies only have targets on the cell surface membrane
Too big to enter cells
Antibodies or small molecule kinase inhibitor more selective
Antibodies
How are antibody targeted therapies administered
IV or SC
How are small molecule kinase inhibitor targeted therapies administered
Orally
What part of tyrosine kinase receptors do small molecule kinase inhibitors bind to
ATP binding site
How can antibody targeted therapies disrupt tyrosine kinase receptors
Bind to regions preventing ligand binding, receptor dimerisation, or ATP binding
How can monoclonal antibodies kill tumour cells directly
Inhibit ligand binding blocking signalling and inducing apoptosis
Deliver toxic drugs conjugated to the antibody
How do monoclonal antibodies kill tumour cells via immune mediated mechanisms
Induce phagocytosis
Complement dependent cytotoxicity
Antibody dependent cell cytotoxicity
How can monoclonal antibodies kill tumour cells by vascular or stromal ablation
Antagonise VEGF
What type of targeted therapy is cetuximab and what is its MOA
monoclonal antibody
Binds to EFGR kinase receptor preventing dimerisation
Kadcycla/trastuzumab emtansine MOA
enters cell bound to antibody -> antibody degraded -> kadcycla causes apoptosis, mitotic arrest, and mitotic catastrophe
Do patients become resistant to kadcycla or herceptin first
Herceptin
Kinase inhibitor targets
Transcription
Receptor tyrosine kinase signalling
Proto oncogenes
What causes drug resistance to targeted therapies
Mutations to target molecules
Why do most HER2 cancer pts eventually become resistant to herceptin
HER2 becomes truncated and the binding site for herceptin is lost but kinase activity is still switched on
Which receptor do erlotinib, gefitinib, afatinib, and osimertinib target
EGFR
Why is osimertinib used after erlotinib
Pts become resistant to erlotinib
Targeted therapy side effects
Acneform Skin rashes EGFR
Dry skin
Itchy skin
Hand foot syndrome VEGF
Hair changes
Dry or red eyes
Red and tender eyelids
High blood pressure
Slow wound healing and blood clotting
Which targeted therapy side effects are specifically associated with EGFR targeting drugs
Skin rashes
Slow wound healing and blood clotting
Which targeted therapy side effects are specifically associated with VEGF targeting drugs
Hand foot syndrome
High blood pressure
Why must cardiac function be assessed before and every 3 months during trastumazab use
Cardiomyopathy is side effect
Why does trastuzumab cause cardiomyopathies
Inhibiting HER2 damages cardiomyocytes
What type of heart failure is caused by trastuzumab
Congestive
