Cancer Chemotherapy Flashcards
(50 cards)
1
Q
what are the 3 main approaches to dealing with established cancers?
A
- surgical excision
- radiotherapy
- chemotherapy
2
Q
what are the 4 types of traditional agent?
A
- alkylating agents
- antimetabolites
- cytotoxic antibiotics
- plant derivatives
3
Q
what are the major groups of alkylating agents?
A
- nitrogen mustards
- ethylemimines
- alkylsulphonates
- hydrazines and triazines
- nitrosoureas
- platinum based compounds
4
Q
what is an example of a nitrogen mustard?
A
cyclophosphamide
5
Q
what is an example of alkylsulphonates?
A
busulphan
6
Q
what are features of busulphan?
A
- has a selective effect on bone marrow, depressing formation of granulocytes and platelets in low dosage and red cells in higher dosage
- little or no effect in lymphoid tissue or GIT
- used in chronic granulocytic leukaemia
7
Q
what type of cancer is busulphan used against?
A
chronic granulocytic leukaemia
8
Q
what are examples of nitrosoureas?
A
- lomustine
- carmustine
9
Q
what are features of lomustine and carmustine?
A
- lipid soluble
- can cross blood-brain barrier
- used against tumours of brain and meninges
10
Q
what type of cancer are lomustine and carmustine used against?
A
tumours of brain and meninges
11
Q
what is an example of a platinum based compound?
A
cisplatin
12
Q
what are features of cisplatin?
A
- water soluble, planar
- containing central platinum atom surrounded by 2 chlorine atoms and 2 ammonia groups
13
Q
how does cisplatin work?
A
- action analogous to alkylating agents: when enters cell Cl- dissociates leaving reactive complex that reacts with water and then interacts with DNA
- it causes intrastrand cross-linking which results in local denaturation of DNA chain
14
Q
what are the major groups of metabolites?
A
- antifolates
- antipyrimidines
- antipurines
15
Q
what is an example of an antifolate?
A
methotrexate
16
Q
what are features of methotrexate?
A
- folate analogue
- usually given orally, can be given IM, IV or intrathecally
- low lipid solubility so does not cross blood-brain barrier easily
- polyglutamated, can be retained within cells for weeks
17
Q
what are some examples of antipyrimidines?
A
- fluorouracil
- cytarabine
- gemcitabine
18
Q
what are features of fluorouracil?
A
- 5-FU
- interferes with thymudylate synthesis (DTMP)
- converted to fraudulent nucleotide FDUMP, cannot be converted into DTMP
19
Q
what are features of cytarabine?
A
- analogue of cytosine but has arabinose and not ribose attached
- undergoes phosphorylation to give cytosine arabinoside triphosphate which inhibits DNA polymerase
20
Q
what are features of gemcitabine?
A
an analogue of cytarabine
21
Q
what are examples of antipurines?
A
- mercaptopurine
- thioguanine
- fludarabine
22
Q
what are features of mercaptopurine?
A
converted to 6-mercaptopurine-ribose phosphate called “Lethal Synthesis”:
- inhibits a number of enzymes in de novo synthesis of purines
- fraudulent nucleotide
23
Q
what are features of fludarabine?
A
in triphosphate form inhibits DNA polymerase
24
Q
cytotoxic antibiotics
A
- anti-tumour antibiotics
- produce their effects mainly by direct action on DNA
25
what are examples of types of cytotoxic antibiotics?
- anthracyclines
- dactinomycin
- bleomycin
- mitomycin
26
what is the main anti-cancer anthracycline antibiotic?
doxorubicin
27
how does doxorubicin work?
- binds to DNA and inhibits both DNA and RNA synthesis
- main cytotoxic action appears mediated through an effect on topoisomerase II (whose activity markedly increases in proliferating cells)
28
what are features of dactinomycin?
- intercalates in minor groove of DNA between adjacent guanosine and cytosine pairs, interfering with movement of RNA polymerase along gene, thus preventing transcription
- similar action anthracyclines on topoisomerase II
29
what are features of bleomycins?
- metal-chelating glycopeptide antibiotics that degrade preformed DNA, causing chain fragmentation
- most effective in G2 phase and mitosis
30
what are features of mitomycin?
- after enzymic activation functions as bifunctional alkylating agent
- cross-links DNA
- may also degrade DNA through generation of free radicals
31
what are examples of plant derivatives?
- spindle poisons
- vinca alkaloids
- taxanes
- camptothecins
- etoposide
32
what do spindle poisons do?
affect microtubule function and prevent mitotic spindle formation
33
what are examples of vinca alkaloids?
- vincristine
| - vinblastine
34
what do vinca alkaloids do?
- bind tubulin
| - prevent polymerisation into microtubules
35
what are examples of taxanes?
- paclitaxel (taxol)
| - docetaxel
36
what do taxanes do?
stabilise (freeze) microtubules
37
what are examples of camptothecins?
irinotecan
38
what do camptothecins do?
bind to and inhibit topoisomerase I
39
what do etoposides do?
inhibits mitochondrial function, nucleoside transport and topoisomerase II
40
what are the main drawbacks of current cancer chemotherapy?
- target cell proliferation, not more lethal properties of invasiveness and metastasis
- non-specific cell killers rather than being aimed at particular changes which make a cell malignant
- development of resistance to anticancer drugs (esp. multidrug resistance)
- some remaining cells (tumour stem), total elimination of malignant cells not possible using therapeutic doses, and host immune response often not adequate to deal with remainder
- patient compliance due to side effects, not completing therapy regimen
41
what are alternative approaches to cancer therapy?
- kill or remove malignant cells
- targeted cytotoxic agents
- specifically inactivate components of oncogene signalling pathway
- employ tissue-specific proliferation inhibitors
- enhance host immune response
- reverse drug resistance
- antisense oligonucleotides
- restore function of tumour suppressor genes
- inhibit tumour growth, invasion, metastasis
- inhibitors of anti-apoptotic factors
42
what anticancer drugs are used for B cell lymphomas?
rituximab
| - targets B cell surface protein
43
what anticancer drug is used for breast cancer?
trastuzumab (herceptin)
| - targets epidermal growth factor receptor
44
what anticancer drug is used for chronic myeloid leukaemia?
imatinib (gleevec)
| - inhibits bcr-abl gene signalling pathways
45
what causes cancer?
1. mutations in DNA resulting in production of altered cells which have changes in proliferating mechanisms
2. changes in the DNA caused by covalent modification:
- spontaneous or genetic predisposition
- ionising radiation or UV radiation
- chemical carcinogens
46
what is replaced in the structure of the antimetabolite, fludaribine?
- F replaces H of adenosine
| - arabinose replaces ribose
47
what is replaced in the structure of the antimetabolite, 5-FU?
F replaces H of uracil
48
what is replaced in the structure of the antimetabolite, gemcitabine?
F replaces H and OH on ribose ring
49
what is replaced in the structure of the antimetabolite, 6-mercaptopurine?
S substitute in purine
50
when are bleomycins most effective in the cell cycle?
G2
