Biological Basis Of Treatment Flashcards
(43 cards)
What is implantation of tumours? Where are implants commonly found?
Mechanical spread of detached clumps of tumour cells, commonly found in peritoneum, ureters and CSF
List all the treatment options of cancer
Surgery Radiotherapy Chemotherapy Hormones Biologically targeted therapy
What are the different forms of chemotherapy?
Primary treatment
Adjuvant - after an operation
Neoadjuvant
Palliative
What is neoadjuvant therapy?
Primary treatment with chemotherapy for patients with a localised tumour. Can be used to assess biological responsiveness of tumours and before surgery to reduce tumour size
Why must chemo be administered in pulses?
Chemo depletes bone marrow as well
Bone marrow cells can recover to a higher level than cancer cells between doses so needs to be given in pulses
When would chemotherapy be given continuously?
If the patient is to have a bone marrow transplant
What are the different types of chemotherapies and what are their sites of action?
Antimetabolites stop DNA synthesis
Alkylating agents bind to DNA and fix it so it cannot be unwound
Intercalating agents affect DNA transcription and duplication
Spindle poisons stop mitosis
What do platinum compounds do?
Form platinated inter- and intra-strand adducts leading to inhibition of DNA synthesis
What is the overall aim of chemotherapy?
To cause DNA damage so that apoptosis is induced
What do topoisomerase-1 inhibitors do?
Inhibit topoisomerase-1
Topoisomerase-1 cleaves a strand of DNA transiently so that the other strand when tightly wound up in supercoiling can be unwound. The strand is then religated and can have normal replication
Inhibits the rejoining of strands causing single and double strand breaks - apoptosis
What does methotrexate do?
Targets the folate cycle which is needed to produce purines for DNA synthesis
What does 5-fluorouracil do?
Inhibits thymidilate synthase which is required for pyrimidine and purine synthesis and the folate cycle
Why are microtubule dynamics critical for mitosis?
They polymerise to attach to the chromosomes
They depolymerise to move sister chromatids away from the metaphase plate during anaphase
What do microtubule binding agents do?
Disrupt microtubule dynamics
- inhibit polymerisation
- stimulate polymerisation and prevent depolymerisation, so that chromatids cannot be pulled apart
What is the aim of combination therapy?
Increased efficacy by
-activity - different mechanisms of action
Problems with combination therapy?
Different mechanisms of action can cause different mechanisms of resistance
Need to consider side effects - safety
List some types of endocrine therapies for breast cancer
Anti-oestrogens eg tamoxifen
Aromatase inhibitors
Progesterones eg megestrol
LHRH agonists eg goserelin
How do aromatase inhibitors work?
Aromatase converts compounds to oestrogens and is located in ovaries and fat
Have less oestrogen if aromatase is inhibited
What are some current endocrine therapies for prostate cancer?
LHRH antagonists eg goserelin Anti-androgens eg flutamide Oestrogen Castration CYP17A1 inhibitor
What are some side effects of anti-androgens?
Less facial hair
Gynaecomastia
Loss of libido
How does a CYP17A1 inhibitor work?
This enzyme is crucial for conversion of pregnenolone and progesterone to testosterone, therefore have less testosterone production
What differences between cancer cells and normal cells can be exploited by biologically targeted therapy?
Cancer cells
- loss of contact inhibition
- increase in growth factor secretion
- increase in oncogene expression
- loss of tumour suppressor genes
Normal cells
- oncogene expression rare
- intermittent or coordinated growth factor secretion
- presence of tumour suppressor genes
What mutation is seen in myeloid leukaemia?
Philadelphia chromosome - a translocation between 9 and 22
- leads to transcription of a protein and leukaemic transformation
- activation of oncogene
What is imatinib?
A Bcr-Abl tyrosine kinase inhibitor
