Oncology 1 Flashcards
Why does cancer occur?
Because of genetic change.
Leading to cells growing out of control
What can cause the genetic change that causes cancer?
- External mutagens such as smoking, UV light etc
- Internal mutagens such as free radical micro environment immune reaction
- Intrinsic error rate - when DNA replication goes wrong
What happens to control DNA replication?
- DNA repair mechanisms in the DNA replication cycle
- Cell cycle checkpoints
If these don’t work, the body can activate tumor suppressors.
If this doesn’t work, it can lead to an error being replicated into the DNA and it can lead to cancer.
What are the hallmarks of cancer?
- Sustaining proliferative signalling - growing in an uncontrolled faction. Genes that drive proliferative signalling
- Evading growth suppressors
- Activating invasion and metastasis
- Enabling replicative immortality
- Inducing anglogenesis
- Resisting cell death
What are the hallmarks of cancer?
- Sustaining proliferative signalling - growing in an uncontrolled faction. Genes that drive proliferative signalling
- Evading growth suppressors
- Activating invasion and metastasis
- Enabling replicative immortality
- Inducing angiogenesis
- Resisting cell death
What are some characteristics of Cancer?
Genomic instability - unstable genetically
Inflammation reactions
Changes in energy reactions/energy metabolism
Evade immune destruction
What is metastasis?
The spread of cancer cells from the place where they first formed to another part of the body.
What is Plasia?
Growth; cellular multiplication
What are the different types of plasia?
Anaplasia - de-differentation of a cell
Dysplasia - altered organization of a tissue
Hyperplasia - increased number of cells in a tissue
What is a tumour?
An abnormal growth
A neoplasm - a mass of tissue that forms when cell divide more than they should
What is a Benign tumour?
A non-invasive growth
Usually not fatal
What is a Malignant tumour?
An invasive cancerous growth
Fatal if untreated
What is invasion?
Migration into local tissue through surrounding membrane
What is metastasis?
The spread of cancer cells from the place where they first formed to another part of the body
What is disease staging?
An assessment of how far the tumour has spread
What is tumour grade?
The degree of de-differentation of a cell in a tumour.
This is assigned by histological examination
What is cytotoxic?
Something that kills cells
What is cytostatic?
Something that inhibits cell proliferation
What is carcinoma and sarcoma?
Carcinoma - malignant tumour of epithelial cell origin
Sarcoma - malignant tumour of connective tissue or muscle
What is chemotherapy?
This refers to cytotoxic therapy.
These drugs will affect fundamental cellular processes - they target processes involved in proliferation.
Has severe ADR
What are key issues with chemotherapy?
There can be drug resistance
And small therapeutic window
What is hormone therapy?
This is where cancers are dependent on a particular hormone for growth
What is the issue with hormone therapy?
The cancer can become hormone independent
How do targeted therapies and biological therapy work?
They target the underlying cause or pathway activated (key genes) causing the cancer.
They can be cytotoxic or cytostatic.
What are the main issues with targeted therapies / biological therapy?
- Not all patients benefit from it - the right drug must be selected for the specific tumour.
- Drug resistance can occur
What is radiotherapy?
When radiation is used to kill cancer cells.
Irradiation of patient or ingestion of radionuclide.
Radionuclide causes DNA damage which causes apoptosis.
What are the ADRs of Chemotherapy?
- Loss of hair
- Diarrhoea
- Nausea and vomitting
- ## Myelosuppression
How are chemotherapeutic drugs administered?
By I.V
What is the caution and contra-indication with Chemotherapy?
Live vaccines cannot be given chemotherapy.
Chemotherapy is usually teratogenic, so cannot be taken when present.
What is Myelosuppression?
A condition in which bone marrow activity is decreased, resulting in fewer red blood cells, white blood cells, and platelets.
Name three examples of Alkylating agents?
Cyclophosphamide
Busulfan
Carmustine
Chlorambucil
What is the mechanism of alkylating agents?
Alkylating agents are electrophilic and react with nucleophiles.
Alkylating agents becomes attached to DNA by the guanine N7 and O6. The two bases cross link together. This stops reproduction.
Alkylation can result in excision of the base, ring-opening or incorrect base pairing.
This could result in a mutation in an essential gene in a cancer cell causing cell death.
However, a mutation in normal cell can promote cancer
What are Anthracyclins?
Cytotoxic antibiotics.
They inhibit topoisomerase
What is Topoisomerase?
An enzyme that regulates DNA supercoiling.
It’s function is to relax the coiling of DNA. It allows the DNA to be uncoiled so that during replication, the strands can be separated.
It allows one strand to be passed through another during replication.
What does Topoisomerase 1 and 2 do?
Topoisomerase 1- cleaves and rejoins single strands
Topoisomerase 2 - cleaves and rejoins both strands
How do Anthracyclins work?
They inhibit Topoisomerase by interchelating between DNA strands and inhibiting re-ligation of strands by topoisomerase II.
What is the caution with Anthreacyclins?
They have a risk of cardiac toxicity by generating free radicals. Especially anthracyclins WITH trastuzumab.
What is an example of Topoisomerase I inhibitor and how does it work?
They work by stabilizing the complex between DNA:Topoisomerase I.
They prevent Topoisomerase I from repairing the break.
Examples are Irinotecan and Topotecan
Example of Topoisomerase II inhibitor and how it works?
They work by stabilizing the complex between DNA Topoisomerase II complex.
This prevents Topoisomerase II from repairing the break. Causing the loss of genetic material.
Examples are:
Mitoxantrone and Teniposide
What is Bleomycin?
A Glycopeptide that chelates Fe2+ and cleaves DNA strands
Three examples of Anti-metabolites?
Fluorouracil
Azathioprine
Methotrexate
Thioguanine
6-Mercaptopurine
What do Thioguanine and 6-Mercaptopurine do?
6-Mercaptopurine prevent the formation of GMP and AMP. Causing a reduction in dATP and dGTP.
Thioguanine prevent the formation of GMP, which causes a reduction in dGTP.
This stop DNA from replicating.
What does GMP and AMP stand for?
GMP - Guanosine monophosphate
AMP - Adenosine monophosphate
What is Azathioprine?
The prodrug of mercaptopurine.
So Azathioprine is converted into mercaptopurine which then prevents the synthesis of AMP or GMP.
What does allopurinol do?
It inhibits the metabolism of mercaptopurine.
So the enzyme that breaks down mercaptopurine is stopped meaning mercaptopurine can work for longer and inhibit DNA proliferation for a longer period.
What are the indications for Azathioprine?
Cancer, transplant rejection, rheumatoid arthritis, myasthenia gravis
What are the cautions for Azathioprine?
Reduce the dose if patient has hepatic or renal impairment.
Do not give live vaccines while using this drug.
What are the ADRs for Azathioprine?
Risk of infection
What does hydroxyurea do?
Inhibits ribonucleotide reductase and ribonucleotide reductase
How does methotrexate work?
It inhibits dihydrofolate reductase, which stops methyltetrahydrofolate being produced. This then means dTMP cannot be made.
What do FH2, FH4, MFH4 and DHFR stand for?
And what are TTP, CTP,dTTP and dCTP ?
- FH2 dihyrofolate
- FH4 - tetrahydrofolate
- MFH4 methyltetrahydrofolate
- DHFR dihydrofolate reductase
- TTP, CTP etc nucleotides
- dTTP, dCTP etc corresponding deoxyribonucleotides
What are the cautions for Methotrexate?
- Avoid in renal impairment, hepatic insufficiency
- Avoid in patients with ascites or plueral effusion because drug can accumulate in the fluid there
What are the ADRs for methotrexate?
- Pulmonary toxicity
- Long term treatment can cause liver cirrhosis
What are the interactions for Methotrexate?
Avoid with Aspirin and NSAIDs - as they could inhibit excretion
Same for Penicillin
Avoid with other antifolate antibiotics such as trimethoprim
Which purines and Pyrimidines cause impaired replication/transcription?
Thioguanine
It is phosphorylated to thiodGTP and is incorporated into DNA and interferes with transcription and replication.
Which purines and pyrimidines cause chain termination?
Fludarabine (purine) and Cytarabine (deoxycytidine analogue) incorporated
into DNA and RNA cause chain termination.
Gemcitabine (deoxycytidine analogue) inhibits ribonucleotide reductase as well as being incorporated into DNA and causes chain termination.
Cladribine incorporated into DNA and causes strand breaks.
Which purines and pyrimidines cause an altered expression?
5-Azacytidine (deoxycytidine analogue) & decitabine incorporated into DNA and alters gene expression
What do Microtubules do?
They play a key role in mitosis: chromosome segregation.
They are essential for cell division of M-phase
What are the two types of Microtubule inhibitors?
- Vinca alkaloids - inhibits polymerization
- Taxanes - inhibits depolymerization causing M-phase arrest and apoptosis
What is an example of Vinca Alkaloids and what are its ADRs?
Example - Vinblastine
ADRs:
- Neurotoxicity
- Inhibition of microtubule-mediated axonal transport
– Paraesthesia
- Loss of tendon reflex abdominal pain
- Constipation
What is the caution and interactions for Vinca Alakaloids?
Caution - ensure that these drugs are not given intrathecally
Interaction - any drugs interfering with metabolism
What is an example of Taxanes and what is its ADR?
Example - Docetaxel
ADR - Hypersensitivity and peripheral neuropathy
How do platinum drugs work?
They modify DNA but attaching themselves to it.
What are examples of platinum drugs, their ADRs and drug interactions?
Examples - Carboplatin, cisplatin
ADRs - Vomitting. Cisplatin can be nephrotoxic and ototoxic
Interactions - other drugs that are nephrotoxic or ototoxic
How are platinum drugs removed?
By glomerular filtration
