Cancer

Question 1

What is cancer?

Answer 1

Populations of cells which lose regulatory control on growth and multiplication.

Question 2

Benign

Answer 2

Localised cancers which cause litter direct harm

Question 3

Malignant cancer

Answer 3

Cancer which results in interferring with key organs, blocking oxygen/nutrient supplies and building up waste, it can lead to serious illness and death.

Question 4

Metastasis

Answer 4

Cancer cells may invade other parts of the body and start new tumours

Question 5

Mutations can occur through:

Answer 5

• 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

Question 6

What are the ways to treat cancer?

Answer 6

• Surgery
• Radiotherapy
• Chemotherapy

Question 7

Surgery

Answer 7

• Some cancers can be cut out
• Limited to those which are localised and accessible
• Some skin cancers)

Question 8

Radiotherapy

Answer 8

Kills the cells using radiation, often after surgery

Question 9

Chemotherapy

Answer 9

• 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

Question 10

Alkylating agents

Answer 10

Alkylating agents form strong bonds with DNA. Drugs with two active groups form crosslinks.

Question 11

Resistance

Answer 11

Cancer cells can develop resistance because they multiply and mutate rapidly.

Question 12

Cisplatin

Answer 12

• 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

Question 13

Doxorubicin

Answer 13

• 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.

Question 14

Topoisomerase inhibition

Answer 14

Less planar extended molecules can bind between between DNA and topoisomerase, stabilising the covalent intermediate and freezing the process.

Question 15

Etoposide

Answer 15

Etoposide and related compounds (semisynthetic) are given intravenously

Question 16

Antimetabolites

Answer 16

Antimetabolites can stop cells making what they need for DNA synthesis

Question 17

Methotrexate

Answer 17

• Methotrexate is a competitive inhibitor of dihydrofolate reductase
• Orally available despite too many HB donors/acceptors by Lipinski’s rules

Question 18

5-fluorouracil

Answer 18

• 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

Question 19

Gemcitabine

DNA-related antimetabolites

Answer 19

• 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.

Question 20

6-Mercaptopurine

DNA-related antimetabolites

Answer 20

• 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.

Question 21

Estogen receptors

Hormone receptors

Answer 21

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

Question 22

Antagonist

Answer 22

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.

Question 23

Dimerization

Answer 23

Changes the conformation so the protein has a differnt shape