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MD2002 > Overview of Cancer Chemotherapy > Flashcards

Overview of Cancer Chemotherapy Flashcards

1
Q

What are the general causes of cancer?

A

mutations in DNA resulting in production of altered cells which have changes in proliferating mechanisms

changes in the DNA caused by covalent modification, spontaneous or genetic predisposition, ionising/UV radiation, chemical carcinogens

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2
Q

Describe the immune response against cancer

A

Immune response against cancer is poor, so are body defences, and high percentage kill needed, biochemistry is same as that of regular cells

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3
Q

Traditional Agents

A

Alkylating agents, antimetabolites, cytotoxic antibiotics, plant derivatives

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4
Q

How do alkylating agents work against cancer?

A

Alkylating agents form covalent bonds with nucleophilic substances in the cell and bind to DNA (intrastrand linking) to cause changes.

It tends to alkylate the 7-Nitrogen guanine residues, which exist in the keto-tautomer, to open the imidazole ring (depurination) ; when this becomes more alkylated it turns into an enol-tautomer, which can mispair with thymine during DNA synthesis to create a mutation which can trigger cell death by apoptosis

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5
Q

Cyclophosphamide (Nitrogen Mustards)

A

Alkylating agent which is activated in liver by P450 enzymes and aldophosphamide is transported to other tissues where it forms phosphoramide (cytotoxic)

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6
Q

What is an example of an Ethylenemine alkylating agent?

A

Thiotepa

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7
Q

What is an example of an Alkyl Sulfonate alkylating agent?

A

Busulfan

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8
Q

What is the function of alkyl sulfonates?

A

Selective effect on bone marrow, depresses the formation of granulocytes and platelets, little to no effect on lymphoid tissue or the GI tract

Used in chronic granulocytic leukaemia

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9
Q

What class of alkylating agent does temozolomide belong to?

A

Hydrazines/Triazines

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10
Q

What are two examples of Nitrosoureas alkylating agents?

A

lomustine, carmustine

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11
Q

In what pathology are Nitrosoureas alkylating agents used, and why?

A

Lipid soluble and can cross the blood brain barrier, may be used against brain tumours

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12
Q

What is an example of a platinum-based alkylating agent?

A

Cisplatin

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13
Q

What is the function of cisplatin in combating tumors?

A

Water soluble, activated by aqueous environment, causes local denaturation of DNA chain

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14
Q

What are the main categories of antimetbolite chemotherapy agents?

A

Antifolates, Antipyrimidines, Antipurines

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15
Q

Name an Antifolate Chemotherapy Agent

A

Methotrexate

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16
Q

Name two anti-pyrimidine chemotherapy agents

A

5FU, gemcitabine

17
Q

What are three examples of antipurine antimetabolite chemotherapy agents?

A

Mercaptopurine
Thioguanine
Fludarabine

18
Q

What are some properties of antifolate antimetabolites?

A

Folate analogue, usually given orally, low lipid solubility, polyglutamated which means it can be retained within cells for weeks

19
Q

How does the antipyrimidine 5FU work to fight cancer?

A

5FU interferes with thymidylate synthesis to prevent formation of DTMP to prevent DNA synthesis - “fraudulent nucleotide”

20
Q

How does cytarabine antipyrimidine work?

A

Analogue of cytosine when phosphorylated it inhibits DNA polymerase

21
Q

How does the gemcitabine antipyrimidine work to fight cancer?

A

Gemcitabine is an analogue of cytarabine: when phosphorylated it inhibits DNA polymerase

22
Q

How does Mercaptopurine work to fight cancer?

A

Mercaptopurine is converted to 6-mercaptopurine-ribose phosphate called “Lethal Synthesis” which inhibits synthesis of purines

23
Q

How does the antipurine fludarabin work to fight cancer?

A

Fludarabin in its triphosphate form inhibits DNA polymerase

24
Q

What are the main classes of antibiotic chemotherapy agent?

A

Anthracyclines
Dactinomycin
Bleomycin
Mitomycin

25
Q

How do anthracycline agents work to fight cancer?

A

Binds to DNA and inhibits both DNA and RNA synthesis and its main cytotoxic action appears to be mediated through an effect on topoisomerase II, the activity of which is markedly increased in proliferating cells.

During replication of the DNA helix, doxorubicin intercalates in the DNA and stabilises the DNA topoisomerase II complex after the strands have been nicked, causing the process to seize up and stop

26
Q

How does dactinomycin work to fight cancer?

A

Dactinomycin intercalates in the minor groove of DNA between adjacent guanine-cytosine pairs, interfering with the movement of RNA polymerase and so preventing transcription.

27
Q

How does bleomycin work to fight cancer?

A

Bleomycin degrades preformed DNA, causing chain fragmentation and release of free bases - it works in the oxidation of iron and generation of superoxide radicals and so is most effective in the G2 phase of cell cycle

28
Q

How does mitomycin work to fight cancer?

A

After its enzymatic activation in cells, mitomycin functions as a bifunctional alkylating agent at O6 of guanine, which crosslinks DNA and may also degrade DNA through the generation of free radicals

29
Q

How do plant-derived spindle poisons work to fight cancer?

A

They affect microtubule function and prevent mitotic spindle formation

30
Q

How do vinca alkaloids work to fight cancer cells? Name two vinca alkaloids.

A

(vincristine, vinblastine) - bind tubulin and prevent polymerisation into microtubules

31
Q

How do plant-derived taxanes work to fight cancer? Name two taxanes.

A

Paclitaxel (taxol), docetaxel

stabilises/freezes microtubules

32
Q

How do camptothecins work to fight cancer? Name one example.

A

binds to and inhibits topoisomerases

irinotecan

33
Q

How does etoposide work to fight cancer?

A

inhibits mitochondrial function, nucleoside transport and topoisomerase II

34
Q

Tumour Lysis Syndrome

A

A metabolic emergency that occurs due to rapid cell lysis & large amounts of cell metabolites in blood during chemotherapy.

Characterised by hyperuricemia, hyperphosphatemia, hyperkalaemia, and hypocalcaemia

Can lead to acute renal failure, cardiac arrest, death

Risk assessment prior to therapy and closely monitored
Dialysis may be required

35
Q

Which chemotherapy agents tend not to cause myelosuppression?

A

vincristine and bleomycin

36
Q

define myelosuppression

A

reduced production of cells which provide immunity, oxygen transport and clotting

MD2002 (50 decks)

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