Cytotoxic Drugs Flashcards
State some characteristics of cancer cells.
Self-sufficient Pro-angiogenic Insensitive to anti-growth signals Non-senescent Anti-apoptotic Pro-invasive and metastatic Evades the immune system
What are the standard treatments for colorectal cancer?
FUFU = 5-fluorouracil + folinic acid
Bevacizumab
What type of drug is 5-fluorouracil?
Anti-metabolite
What is the main mechanism of action of 5-FU?
Inhibition of thymidylate synthase
This is important in the generation of THF (tetrahydrofolate), which is required for the generation of nucleotides for the growing DNA chain
What is the mechanism of action of Bevacizumab?
It is a monoclonal antibody against VEGF (ligand)
It inhibits angiogenesis and so strangles the blood supply of the tumour
What is the standard treatment for non-small cell lung cancer?
PLATINUM treatment + another drug
Cisplatin + Etoposide
Carboplatin + Gemcitabine
What type of drug is cisplatin and what is its mechanism of action?
Alkylating-like agent
It cross-links guanine residues in DNA and forms adducts
These adducts inhibit DNA synthesis and repair leading to apoptosis
What type of drug is etoposide and what is its mechanism of action?
Topoisomerase II inhibitor
Topoisomerase II cuts a bit of DNA to allow it to unwravel so that substrates required for DNA replication can gain access to the DNA
Etoposide will lead to strands being cut and unable to re-ligate –> no replication
What type of drug is gemcitabine and what is its mechanism of action?
Antimetabolite
Inhibits ribonucleotide reductase
Inhibits DNA polymerase
Incorporates into DNA causing chain termination
What is the treatment of advanced non-small cell lung cancer?
PLATINUM therapy in combination with a TAXANE or VINCA ALKALOID
If EGFR mutations are present = ERLOTINIB also recommended
Name a taxane.
Docetaxel
Name a vinca alkaloid.
Vinorelbine
What feature of microtubules is essential for its role as mitoticspindles?
Dynamic instability – the ability to grow from one side and shrink from the other allows the spindle to rapidly lengthen and shrink
Describe the difference in the mechanism of action of taxanes andvinca alkaloids.
Taxanes – inhibit microtubule DISASSEMBLY
Vinca alkaloids – inhibit microtubule ASSEMBLY
What is the overall effect of these drugs?
They inhibit spindle formation meaning that the chromosomes can’t separate during mitosis and the cells can’t divide
What type of drug is Erlotinib?
Small molecule inhibitor
What receptor does Erlotinib target?
EGFR (selective inhibitor)
Describe the mechanism of action of Erlotinib.
It binds to the intracellular domain of EGFR and prevents auto-phosphorylation
This prevents intracellular signaling of EGFR and hence reduces cell proliferation
What are the three main treatment options for breast cancer?
Hormone therapy
TAC regimen
Trastuzumab
Which drugs make up the TAC regimen?
Doxorubicin
Docetaxel
Cyclophosphamide
Describe the mechanism of action of cyclophosphamide.
It is an alkylating agent/nitrogen mustard
It forms covalent bonds with DNA and RNA, which prevents DNA replication and transcription
It cross-links guanine residues in the DNA
Describe the mechanism of action of doxorubicin.
Intercalates DNA and poisons topoisomerase II
This inhibits DNA synthesis and replication –> cells are unable to divide
What is trastuzumab used to treat?
Her-2 enriched breast tumours
What does the Her-2 receptor form a dimer with?
EGFR
Describe the mechanism of action of trastazumab.
It is a monoclonal antibody that binds to the extracellular region of the
Her-2/neu receptor and prevents the intracellular actions of the Her-2/EGFR heterodimer
