Targeting Cell Proliferation + Survival Flashcards
What’s the rationale for chemo?
Surgery + radiotherapy excellent for treating localised
BUT cancer can metastases
Can have palliative effects = symptom relief + increased QoL
Describe the cell cycle
G1 phase = growth
Cells grow + makes protein
Checks conditions are right to continue
S phase = synthesis
Cell duplicates DNA
Ensures each new cell contain same genetic information
G2 phase = growth
Cells grow + prepare for division
Checks for errors in copied DNA
M phase = mitosis + cytokinesis
Cell divides into 2 identical daughter cells
Mitosis separates the copied DNA, and cytokinesis splits the cell
What different drugs are there?
Anthracyclines
Antimetabolites
Vinca alkaloids
Taxanes
Alkylating agents
Give a combo of drugs to target different parts of the cell cycle = only target one = potential resistance
What are examples of cycle non-specific drugs?
Alkylating agents = Cyclophosphamide
Platinum agents = Carboplatin + Cisplatin
What are examples of S phase target drugs?
Antimetabolites:
Folate analogues = methotrexate
Purine analogues = mercaptopurine
Pyrimidine analogues = 5FU
What are examples G1 target drugs?
Anthracyclines = Doxorubicin
Hormonal agents = Tamoxifen
What are examples of M phase target drugs?
Taxanes = Paclitaxel + Docetaxel
What are examples of G2 phase target drugs?
Epipodophyllotoxin derivatives = Etoposide + Teniposide
What is the MoA of Vinca Alkaloids?
Blocks tubulin polymerisation to form microtubules
What is the MoA of Taxanes (Paclitaxel)?
Promote microtubule polymerisation
Inhibit depolymerisation
Stabilisation of microtubules + arrest cells in mitosis
Describe the oncogenes
Activity = stimulate cell cycle progression
Mutation in cancer = gain of function
Describe the tumour suppressors
Activity = inhibit cell cycle progression
Mutation in cancer = loss of function
What are CDK?
Cyclin-dependent kinases
Key cell cycle proteins to regulate their activity + modulate cell cycle progression
What is an example of a CDK inhibitors?
Palbociclib
Inhibits CDK4-cyclin binding
OD orally
What is PARP inhibitors?
Prevent DNA repair in cancer cells
= increases cancer cell death
= improve success of chemo + radiotherapy
What are the 3 types of resistance?
Inherent = cells NOT sensitive to drugs
Apparent = cell are sensitive BUT drug does NOT get there
Acquired = cells initially sensitive BUT develop resistance following prolonged exposure
Multidrug resistance = cells exposed to single drug develops resistance to multi resistance
