Cancer Flashcards
What is cancer?
Populations of cells which lose regulatory control on growth and multiplication.
Benign
Localised cancers which cause litter direct harm
Malignant cancer
Cancer which results in interferring with key organs, blocking oxygen/nutrient supplies and building up waste, it can lead to serious illness and death.
Metastasis
Cancer cells may invade other parts of the body and start new tumours
Mutations can occur through:
- Chemical damage (smoking, pollution, diet, medicinal side effects…)
- Viruses (Hepatitis causes liver cancer, HPV causes cervical cancer…)
- Genetics (BRCA gene raises risk of breast cancer…)
- Random mistakes in biochemistry
What are the ways to treat cancer?
- Surgery
- Radiotherapy
- Chemotherapy
Surgery
- Some cancers can be cut out
- Limited to those which are localised and accessible
- Some skin cancers)
Radiotherapy
Kills the cells using radiation, often after surgery
Chemotherapy
- Using medicines (i.e. chemicals) to kill the cancer cells.
- Anticancer medicines are generally cytotoxic
- Drug design will aim to make compounds more toxic to cancer cells
- Not easy – the cells come from the same source as normal cells
- Risk of death lowers barrier to side effects and intravenous administration
Alkylating agents
Alkylating agents form strong bonds with DNA. Drugs with two active groups form crosslinks.
Resistance
Cancer cells can develop resistance because they multiply and mutate rapidly.
Cisplatin
- Cisplatin is used intravenously for various cancers, often in combination.
- Side effects include nausea/vomiting.
- Cancer cells develop resistance to cisplatin as they multiply rapidly and mutate
Doxorubicin
- One of the most effective anticancer drugs
- Used to treat broad spectrum of cancers
- Not orally active (6 HB donors, 9 HB acceptors, Mw = 543, LogP = 0.31) – intravenous administration
- Liposome formulation keeps the drug in the bloodstream longer – reduces elimination.
Topoisomerase inhibition
Less planar extended molecules can bind between between DNA and topoisomerase, stabilising the covalent intermediate and freezing the process.
Etoposide
Etoposide and related compounds (semisynthetic) are given intravenously
Antimetabolites
Antimetabolites can stop cells making what they need for DNA synthesis
Methotrexate
- Methotrexate is a competitive inhibitor of dihydrofolate reductase
- Orally available despite too many HB donors/acceptors by Lipinski’s rules
5-fluorouracil
- 5-Fluorouracil inhibits thymidylate synthase
- Given intravenously because absorption is variable between patients
- Used to treat a range of cancers, looks like a uracil but has a fluorine instead of a hydrogen
- Quite small
- Stops the production of dTMP and therefore stop the production of DNA synthesis
- Amount that enters the bloodstream varies
- Recognised by most of the enzymes
Gemcitabine
DNA-related antimetabolites
- Gemcitabine is phosphorylated in vivo and incorporated into DNA to create faulty DNA which cannot be repaired, resulting in cell death.
- It is given intravenously for a variety of cancers in combination with other drugs.
6-Mercaptopurine
DNA-related antimetabolites
- 6-Mercaptopurine also gets transformed into nucleoside triphosphates and incorporated into DNA, causing cell death by impeding various enzymes
- Typically used for acute leukaemias, being more effective in children.
Estogen receptors
Hormone receptors
Estrogen receptors (ER) are intracellular receptors – they operate in the cytosol – but like membrane receptors dimerise on binding, and migrate to the nucleus where they act as transcription factors leading to cell proliferation
Antagonist
Molecule binds in the same site as the natural hormone but results in the opposite effect - stop the signalling pathway which encourages the cells to grow.
Dimerization
Changes the conformation so the protein has a differnt shape
