Targeted therapies in breast cancer Flashcards
What are some of the pathological considerations of breast cancer/+treatment
Histology (classification)
I.e. is it ‘in situ carcinoma’ or infiltrating carcinoma
How can the histology of breast cancer be tested?
DNA microarray analysis
What is the ER pathway?
Oestrogen binds to the ER in the nucleus promoting proliferative pathways.
The extra-nucleus binding of ER modulates downstream signalling pathways to promote proliferation.
Which targeted therapy drugs target the ER pathway?
How can these drugs be used?
Tamoxifen
Ais
Fulvestrant
These drugs can be used in combination or alone
Which targeted therapy drugs target the mTOR/PI3K/AKT pathway?
How can these drugs be used?
PI3K inhibitor: alpelisib
mTOR inhibitor: everolimus
targeting these pathways in combination works better than on their own
What is the mTOR/PI3K/AKT pathway?
Proliferation pathway in breast cancer
It is unregulated in most cancers (up regulation of cyclin D = cells move from G1 to S phase faster = proliferation)
What is the CDK pathway?
Transition from G1 to S phase is regulated by cyclin D-CDK4/6 pathway
PI3K/mTOR/AKT promotes cyclin D pathway
Which targeted therapy drugs target the CDK pathway?
MOA
Abemaciclib
Palbociclib
Ribociclib
They prevent cells from progressing in the cell cycle (senescence)
What is the HER2 pathway?
HER2 is a tyrosine kinase receptor.
It is only activates when dimerised, homodimerised or heterodimerised
It is unregulated in HER2+ breast cancers
What are the target sites of HER2 drugs and give examples for each
ATP binding site; lapatinib
Extracellular juxtamembrane domain; trastuzumab
Dimerization site; pertuzumab
What is the VEGF pathway responsible for?
Angiogenesis
What type of cancer is the VEGF pathway linked to?
Triple negative breast cancer
Basal like breast cancer
Which drug(s) target the VEGF pathway?
Bevacizumab
What are PARP proteins?
Critical for single strand break repair and base excision repair pathways
Give 2 examples of PARP inhibitors
Olaparib
Talazoparib
