What are the potential ways that tumours can spread?
What is local spread of cancer?
Direct involvement of surrounding structures
What cancers spread via the lymphatics?
What cancers spread via the blood?
- Later stage carcinomas
What happens in implantation spread of cancer?
There is mechanical spread of detatched clumps of tumour cells to the peritoneum, ureters, or CSF
What are the treatment options for cancer?
- Biologically targetted therapy
In what ways can chemotherapy be used in treating cancer?
- Radical primary treatment
- Adjuvant therapy
- Neoadjuvant therapy
- Palliative care in advanced disease
Where is chemotherapy used as a radical primary treatment?
In haemotological malignancies, such as lymphomas and leukaemias
What is the definition of adjuvant chemotherapy?
Post-operative treatment in a patient at high risk of microscopic metastases after the removal of the primary tumour
What is neoadjuvant chemotherapy?
Primary treatment of patients with clinically localised tumour - use chemotherapy upfront to improve the outcome of the primary therapy
What are the advantages of neoadjuvant chemotherapy?
- Can assess the biological responsiveness of the tumour
- May allow for conservation surgery
- May achieve pCR (pathological complete response
What determines the rate of tumour growth?
- Growth fraction
- Duration of cell cycle
- Rate of cell loss
What does topoisomerase 1 do?
It causes transient single strand cleavage, relaxes the strand, and then sticks it back together
How does topoisomerase 1 inhibition work?
You get binding to the TOPO 1-DNA complex, without affecting the cleavage region. This means that the enzyme cannot rejoin the DNA, resulting in a double stranded break and therefore cell apoptosis
What is the advantage of a unique tumour-activated agent?
It wouldn't affect normal tissue, and so minimises side effects
Give an example of a tumour activated chemotherapy agent?
What is the mechanism of action of xeloda?
- It is absorbed in the intestine
- It is converted to 5'-DFCR CyD and then 5'-DFUR
- 5'-DFCR CyD and 5'-DFUR are transported into the tumour tissue, where they are converted to 5-FU
- 5-FU blocks DNA replication
What happens to spindle microtubules once chromosomes are aligned at the metaphase plate?
They depolymerise, moving sister chromatids towards opposite poles
How do micro-tubule binding agents affect microtubule dynamics?
- Inhibit polymerisation
- Stimulate polymerisation and prevent depolymerisation
What does it need to be ensured if combination therapy is to improve activity?
- Drugs have a different mechanism of action
- Drugs have different mechanisms of resistance
What needs to be ensured if combination therapy is to be safe?
They have compatible side effects
What is P-glycoprotein?
An ATP-powered efflux pump
What does P-glycoprotein do?
Pumps cytotoxic agents out of the cells against the concentration gradient
What repair pathway is employed in single-stand breaks?
Base excision repair
What enzyme is used in base excision repair?
What repair pathway is employed in double stranded DNA breaks?
What enzymes are used in recombinational repair?
- ATM in homologous recombination repair
- DNA-PK in non-homologous end joining
What repair pathway is employed when bulky adducts are added to DNA?
What enzymes are used in nucleotide-excision repair?
What repair pathway is employed with insertions and deletions to DNA?