Cancer Chemotherapy Flashcards
What are the 3 main approaches to dealing with established cancers?
- Surgical excision
- Radiotherapy
- Chemotherapy
What are the 4 main types of traditional chemotherapy agents?
- Alkylating agents
- Antimetabolites
- Cytotoxic antibiotics
- Plant derivatives
What is the mechanism of action of alkylating agents?
- They form covalent bonds with suitable nucleophilic substances
- They cause intrastrand cross-linking of DNA which causes knock on effects to then kill the cancer cells
WHat are the 6 major groups of alkylating agents?
- Nitrogen mustards
- Ethylenimines
- Alkylsulphonates
- Hydriazines and triazine s
- Nitrosoureas
- Platinum based compounds
Give an exmaple of a nitrogen mustard
Cyclophosphamide
Give an example of an Ethylenimine
Thiotepa
Give an example of an alkylsulphonate
Busulphan
Give an example of a hydrazine/triazine
Temozolomide
Give an example of a nitrosoureas
lomusine or carmustine
Give an example of a platinum based compound
Cisplatin
What are antimetabolites?
Look like normal natural molecules so are taken up by cells but when they are taken up by cancer cells they mess up the metabolic pathway
What are the 3 main groups of antimetabolites?
- Antifolates
- Antipyrimidines
- Antipurines
Give an example of a commonly prescribed antifolate
Methotrexate
Give an example of an antipyrimidine
5-FU or gemcitabine
Give an example of an antipurine
Mercaptopurine or thioguanine
What are the 4 main types of cytotoxic antibiotics?
- Anthracyclines
- Dactinomycin
- Bleomycin
- Mitomycin
Give an example of an anthracycline
Doxorubicin
What are the two main mechanisms of action of plant derivatives?
- Spindle poisons - inhibit microtubule function during metaphase
- Topoisomerase inhibitors (type 1 or 2) to do with the unwinding of the DNA helix
What are the 2 main types of spindle poisons (plant derivatives)?
- Vinca alkaloids
- Taxanes
Name vinca alkaloid drug
Vincristine, vinblastine
Name a taxane drug
- Paclitaxcel (taxol)
- Docetaxel
What are the two types of topoisomerase inhibitor (plant derivative)?
- Camptothecins (top 1)
- Etoposide (top 2)
Name a camptothecin drug
Irinotecan
What are the main drawbacks of chempotherapy of cancer?
- Target cell proliferation not the more lethal properties of invasiveness and metastasis
- Non-specific cell killlers rather than being aimed at the particular changes which maje a cell malignant
- The development of resistance (particularly multidrug resistance) to anticancer drugs
- ## Leaves some remaining cells
What kind of cells are often affected by chemotherapy drugs?
- Bone marrow
- GI
- Hair
- Skin
- Mucosa
What side-effect can anthracyclins cause?
Cardiotoxicity
What side-effect can vinca alkaloids cause?
Neuropathy
What is a specific side-effect of high dose cisplatin?
Ototoxicity (ear problems)
What is Tumour-Lysis syndrome?
- An acute side-effect and a metabolic emergency
- Occurs due to rapid cell lysis (death) and large amounts of cell metabolites in blood
- If untreated can lead to acute renal failure, CA and death
What does tumour lysis syndrome show in the blood (in terms of metabolites)?
- Hyperuricaemia
- Hyperphosphataemia
- Hyperkalaemia
- Hypocalcaemia
What property of human cells makes them more affected by chemotherapy?
Shorter life-span
What does emetogenic mean?
Causing nause and vomitting
What chemotherapy drug can cause especially high emetogenic affects?
Cisplatin
What specific side-effects can chemotherapy cause to the GI system?
- Nausea
- Vomitiing
- Diarrhoea
- Constipation
- Loss of appetite
- Ulceration, dry mouth pain, taste alterations
What monoclonal antibody is used against B cell lymphomas and targets a specific B cell surface protein?
Rituximab
What monoclonal antibody is used against breast cancer?
Trastuzumab
What receptor does trastuzamab target?
Epidermal growth factor receptor 2 (HER2/ERBB2)
What drug is used against CML?
Imatinib
What gene-signalling pathway soes imatinib specifically inhibit?
bcr-abl gene signalling pathways
What factors does personalised medicine take into account when prescribing a drug for cancer?
- Family history
- Socioeconomic circumstances
- Enviromental
- Genomic/genetic testing
- Proteomic profiling
- Metabolomic analysis (study metabolites)
What are the 4 Ps of Personalised Medicine?
- Predictive
- Personalised
- Preventative
- Participatory
What are the aims of stratified medicine?
- Improved prevention based on underlying predisposition
- Earlier diagnosis of disease as a result of identifying abnormality earlier
- More precise diagnosis based on cause and
- Targeted interventions through the use of companion diagnostics to identify and stratify patients for effective treatment
What drug is used to treat non small cell lung cancer (EGFR mutation)?
Erlotinib
Would erlotinib be used in a NSCLC involving a KRAS mutation?
No
What drug would be used in a NSCLC involving an ALK rearrangment?
Crizotinib
What monoclonal antibody would be used in the treatment of colorectal cancer?
Cetuximab
When would cetuximab not be used in the treatment of colorectal cancer?
If a RAS mutation was present (KRAS/NRAS mutation)
When would Vermurafenib be used?
Melanoma (with a BRAF-activating mutation)
Roughly 40 - 60% of melanomas
What drug would be used for a melanoma with an NRAS mutation?
MEK inhibitors / combinations
When would imatinib be used?
- CML
- OR KIT mutations (3% of melanomas)
What drug is used to repair DNA after chemotherpy?
MGMT
What can FISH (fluorescent in situ hybridisation) be used for?
Diagnosis of cancer (can be used to determine what specific type)
What is nivolumab?
- Fully human IgG4 PD-1 immune-chechpoint-inhibitor antibody that disrupts PD-1-mediated signaling
- Restores antitumour immunity
What is checkpoint inhibitor therapy?
Reactivates immune system to see cancer cells
What monoclonal antibody is used in metastic melanomas (it is an anti-CTLA-4 antibody)?
Ipilimumab
What are PD-1 and PD-L1?
- PD-1 is found on T cells and acts as on ‘off switch’ that helps keep other T cells from attacking other cells in the body
- PD-1 attaches to PD‑L1, a protein found on some normal (and cancer) cells
- This interaction basically tells the cell to not attack the other cells
- Prevents auto-immune disease
- PD-1 = receptor PDL-1 = ligand
