molecular pathology of cancer treatments Flashcards
name some chemotherapy drugs and outline how each works.
- vinblastine - attaches to microtubules in the cell which prevents them contracting, causing them to constantly stay in metaphase
- etoposide - binds with tropoisomeraseII (enzyme used in dna replication) preventing it from working so dna replication cant happen
- ifoamide and cisplatin - binds to dna cross links meaning cell cant divide
what are the cons of chemotherapy?
- Not selective to tumour cells, also prevent normal cells from dividing eg gut lining and bone marrow
- This is why theres so many side effects of chemotherapy
- Not useful for cells with slower dividing tumours
outline the pros of chemotherapy drugs
- good for fast dividing tumours such as:
- Germ cell tumours of testis
- Acute leukemias
- Lymphomas
- Embryonal paediatric tumours
- Choiocarcinomas – tumour of the placenta
Why are cancer cells much more active and cause tumours much faster than normal cells?
- Lack of apoptosis due to mutations in P53 gene for example
- Also therefore more cells to divide
- Divide much quicker
outline the molecule mechanism of the drug cetuximab.
- this drug is a monoclonal antibody which blocks the epidermal growth factor receptor (EGFR) to prevent epidermal growth factor (a molecule in the blood) from binding to it
- when this growth factor binds to the receptor, it usually causes a chemical cascade to occur in the cell, promoting cell proliferation
- however when this is blocked it prevents the chemical cascade from occuring, meaning cell proliferation isnt promoted, containing the growth of the cell
outline the molecular mechanisms of the drug herceptin, when its being used as a chemotherapy drug for breast cancer.
- herceptin is a monoclonal antibody against human epidermal growth factor-2 (Her-2)
- her-2 sits on the membrane of these cells and becomes activated when it bumps into another her-2 or a her-3
- in certain tumours, her-2 is overexpressed meaning they’re more likely to bump into each other
- herceptin is a monoclonal antibody which binds to the outside of the receptor (this alone doesnt work because nothings trying to bind to the antibody so wont do anything) but it shoves the receptor inside the cell and it becomes endocytosed and broken up
- in turn reducing the amount of her-2 receptors reducing the liklihood they will bump into each other
in how many cases of breast cancer is the her-2 gene amplified in?
20%
when creating chemotherapy drugs, its ideal if we find the difference between normal and cancer cells and target this difference, what are ways in which we can find this difference?
- gene arrays
- proteonomics
- tissue microarrays
what characteristics of cancer is the HER-2 gene associated with forming?
large size
high grade
aneuploidy (abnormal amount of chromosomes)
negative oestrogen receptor status
independent adverse prognostic factor
define the term targeted chemotherapy and outline why its most beneficial.
exploits some difference between cancer cells and normal cells to target drugs to the cancer cells
more effective
less side effects
Cetuximab (Erbitux)
chimeric IgG humanised monoclonal antibody
binds competitively to extracellular domain of EGFR
antitumour activity in xenograft models
blocks production of VEGF, interleukin 8, bFGF
Herceptin - trastuzumab
chimeric mouse-human monoclonal antibody
directed against the extracellular domain of Her-2 protein
how do we detect HER-2 amplification?
- flourescent in situ hybridisation
- immunohistochemistry
briefly outline the molecular mechanisms of the therapy CAR-T
- blood taken from patient
- filter out immune T cells
- a virus used to put genes into t cells to recognise and target cancer cells
- modified cells duplicated in lab
- modified cells injected back into patient
