overview of cancer chemotherapy Flashcards
what is cancer?
how do cancer cells differ from normal cells?
what are 3 characteristics of cancer cells?
neoplasia - “new growth”
- the uncontrolled proliferation of abnormal forms of the body’s own cells (mutated cells to form a cancer mass)
- cancer cells differ from normal cells in their behaviour
- they exhibit characteristics not seen in normal cells:
1. uncontrolled proliferation
2. invasiveness (invade locally)
3. metastases (spread)
causes of cancer are all genetically based, what are 2 main things which cause the genetic change?
- random mutations in DNA resulting in production of altered cells which have changes in proliferating mechanisms
- changes in the DNA caused by covalent modification (carcinogenesis)
- spontaneous or genetic predisposition
- ionising radiation or UV radiation
- chemical carcinogens
hat is the biggest risk factor of cancer?
age
what are the 3 main approaches to dealing with established cancers?
3 main approaches to dealing with established cancers:
- surgical excision
- radiotherapy
- chemotherapy
what are issues to do with antimicrobial treatment against cancer?
issues to do with antimicrobial treatment
- generally immune response and body defences to ani-microbrial is good
- only a partial percentage of cells are needed to be killed becauseimmune response does the rest
- biochemistry is different, since different microbes are involved
what are issues to do with anti-cancer treatment against cancer?
- immune response is poor against cancer
- body defences is also poor
- percentage to killed is variable, cancer is more looked at llike in a way to make it managable rather than making it erradicated
- the biochemistry is the same since it is our body’s own cells
list four types of traditional agents against cancer
four types of traditional agent
- alkylating agents
- antimetabolites
- cytotoxic antibiotics
- plant derivatives
alkylating agents:
how common of an anti-cancer drug are they?
what is their main property?
what is their main mechanism to killing cancer cells?
- Most commonly employed anticancer drugs, and they are a;lso synthetic
- These are compounds which have the property of forming covalent bonds with suitable nucleophillic substances (DNA) in the cell under physiological conditions
- they bind to intrastrand DNA helix multiple times cause a Intrastrand crosslinking of DNA which causing a deleterious mutation and kills the cell
alkylating agents:
explain the mechanism behind alkylating agents
- Normally guanine residues in DNA exist predominantly in the keto tautomer (a particular form, conformational change) - within the guanine base pair
- This allows them to readily make Watson-Crick base pairs by hydrogen bonding with cytosine (changes the chemical properties)
- When the 7 nitrogen of guanine is alkylated it becomes more acidic and the enol tautomer is formed. (i.e. keto to enol)
- This modified guanine can mispair with thymine residues during DNA synthesis. i.e. G-T not G-C, creating a mutation (cell would pick up this damage and cause cell death
alkylating agents:
list 6 major groups of alkylating agents and an example of each
- Nitrogen mustards – e.g. cyclophosphamide
- Ethylenimines - e.g. Thiotepa
- Alkylsulphonates - e.g. Busulphan
- Hydrazines and Triazines – e.g. Temozolomide
- Nitrosoureas – e.g. lomustine, carmustine
- Platinum based compounds – e.g. cisplatin
antimetabolites:
list 3 major groups of antimetabolites and an example of each and their mechanism of action
-
antifolates - e.g methotrexate
- blocks DHFR pathway (folate metabolism) -
antipyrimidines - e.g 5-FU, gemcitabine
- inhibits DNA polymerase -
antipurines - e.g mercaptopurine, thioguanine
- inhibits DNA polymerase (prevents replication, transcription)
cytotoxic antibiotics - derived from natural environment:
list 4 major examples of cytotoxic antibiotics and their mechanism of action
-
anthracyclines - e.g doxorubicin
- It binds to DNA and inhibits both DNA and RNA synthesis -
dactinomycin
- intercalates in the minor groove of DNA between adjacent guanosine cytosine pairs, interfering with the movement of RNA polymerase along the gene and thus preventing transcription -
bleomycin
- Their action on DNA is thought to involve chelation of ferrous iron and interaction with oxygen, resulting in the oxidation of the iron and generation of superoxide and/or hydroxyl radicals -
mitomycin
- It cross-links DNA and may also degrade DNA through the generation of free radicals.
plant derivatives:
list 5 plant derivatives which are used as anti-cancer drugs and their main actions of mechanism
- Spindle poisons
– affect microtubule function
and prevent mitotic spindle formation - Vinca alkaloids, e.g. Vincristine, vinblastine
- bind tubulin and prevent polymerisation into microtubules
- Taxanes - Paclitaxel (taxol), docetaxel
- stabilise (freeze) microtubules
- Camptothecins, e.g. irinotecan
- Bind to and inhibit topoisomerase I
- Etoposide
- Inhibits mitochondrial function, nucleoside transport and topoisomerase II
list 4 other anti-cancer drugs and their actions of mechanism
- Hormones (hormone inhibitors) (used in breast and prostate cancer)
- Monoclonal antibodies - newer class of chemical made to be specific to cancer cells, tend to hit proteins on cell surfaces (receptors)
- Protein kinase inhibitors - hit intracellular receptors
- Miscellaneous agents
what are 4 drawbacks of chemotherapy of cancer?
- non specific target: and targets cell proliferation not the more lethal properties of invasiveness and metastasis of the cancer
- Non-specific cell killers rather than being aimed at the particular changes which make a cell malignant
- The development of resistance (particular multidrug resistance) to anticancer drugs (the tumour eventually becomes drug resistant)
- Leaves some remaining cells (the drugs aren’t 100% effective)
