Part 7: Cancer Treatments 1 Flashcards
1
Q
define cancer
A
disease characterized by a defect in normal control mechanisms that govern cell survival, proliferation and differentiation
2
Q
loss of ___ allows tumors to grow excessively and disrupt normal physiologic functions or organs and tissues
A
regulatory components
3
Q
what are some cancer risks we cannot control?
A
age, sex, race, genetics
4
Q
which sex is at higher risk of cancer
A
men, but women are close approaching
5
Q
does the presence of certain genes or biomarkers that are linked to cancer mean that you will definitely develop cancer?
A
no
6
Q
what are the most important determinants of cancer development?
A
environmental factors
7
Q
what are the environmental factors that affect cancer development?
A
UV and radiation exposure, chemicals iin smoking tobacco
8
Q
what virus has been shown to increase the risk of cervical cancer for women?
A
HPV
9
Q
t/f lifesytle conditions like diet and exercise influence cancer risk
A
t
10
Q
t/f cancer is the leading cause of death in canada
A
t
11
Q
what are the 4 most common cancers in Canada?
A
- lung cancer
- breast cancer
- colorectal cancer
- Prostate cancer
12
Q
t/f survival rates of cancer are increasing
A
t
13
Q
t/f tumour cells originate from normal cells
A
t
14
Q
how does cancer growth start?
A
chemical or physical carcinogen causes mutation
15
Q
what happens in the “promotion” stage of cancer development?
A
cell division promoted by promoting and growth factors
16
Q
t/f cancer initiators can also be promotors
A
t
17
Q
an example of an initiator that can also be a promotor
A
cigarette smoke
18
Q
do all cell mutations go on to daughter cells? why or why not?
A
no; because sometimes the cells can fix the mistake before or die before reproducing
19
Q
t/f there can be multiple mutations within a population of cells
A
t
20
Q
what happens in the “progression” stage of cancer development?
A
transformation to malignancy, further mutation and variability in the tumour
21
Q
what does it mean when a tumour becomes malignant?
A
tumour has transformed so that its cellular process are no longer tightly controlled and regulated like normal cells
22
Q
a hallmark of tumour biology is that the cells become invasive and take over ___
A
neighbouring tissues
23
Q
what is stage 0 cancer?
A
early cancer, not detectable, stays at site of origin (in situ)
24
Q
what are stages 1-3 cancer?
A
tumour is increasing in size and spread
25
what is stage 4 cancer?
tumour has invaded into other tissues and there is metastasis
26
what is contact inhibition?
in normal cells, when they come in contact with a neighbouring cell, they stop growing
27
do cancer cells have contact inhibitions?
no
28
as a tumour gets larger, it requires additional nutrinets to feed its growth, so it recruits ___ and ___. to meet its metabolic needs
blood vessels and lymph nodes
29
at what stages are tumours typically detected?
2-3
30
why are tumours typically detected at stages 2-3?
onset of symptoms
31
in colon cancer, the invasion of the tumour across the colon membrane is likely to cause what detectable symptom?
blood in the stool
32
in what stage does a tumour have a rich blood and lymph supply?
stage 4
33
what are the common sites of secondary tumours that come off a stage 4 tumour?
areas that are highly perfused (liver, brain, lungs)
34
what are the 3 main ways to treat cancer?
1. surgical removal
2. radiation
3. chemotherapy
35
radiation is very effective at killing cancer cells, so why is it limited?
limited to cells near the surface of the skin (skin, head and neck cancers_
36
does radiation specifically target cancer cells ?
no
37
chemotherapy is also called ____ (3)
1. antineoplastic drugs
2. anticancer drug
3. immunotherapy
38
what are antineoplastic drugs?
drugs that prevent the growth of abnormal cells (neoplasms)
39
how do antineoplatic drugs work to prevent abnormal cell grwth?
interfering with aspects of the cell cycle and preventing rapidly dividing cells from proliferating
40
there are some newer drugs that target tumour ___ or ____ that have been shown to be increased in cancer cells
biomarkers and cellular processes
41
what is the aim of immuotherapy in cancer treatment?
to enhance the responsiveness of the host immune system to be able to recognize tumour cells and remove them
42
why is it such a challenge to only target cancer cells in chemo?
tumour cells originate from host cells, so they have all the same cellular parts as our normal cells
43
what is a typical target of antineoplastic drugs?
quickly dividing cells
44
does the approach to target "rapidly dividing cells" spare all healthy cells?
no
45
t/f the max tolerable dose of anti-cancer medications should be used
true
46
t/f the chosen cancer treatment must be tolerable so the whole course of treatment can be completed
t
47
why is it typical to give multiple anti-cancer agents with different MOAs?
used to increase tumour killing rate; reduce resistance and facilitate low dose to protect against ADRs
48
why is chemo typically given in cyclic rounds?
reduce ADR by allowing healthy tissues to repair themselves
49
many tumours are apprximated to follow a ____ growth pattern
exponential
50
what is the typical size of a tumour that can be detected?
1cm3, small green pea
51
what is reccurence of cancer?
after removal of cancer, some cells remain and start to grow new tumours
52
if chemo treatments are spaced too far apart, what can happen?
cancer cell #s increase too much
53
what are the 2 key processes of the cell cycle that allow proliferation of tumour cells?
1. S phase (making copy of DNA
| 2. M phase (mitosis)
54
what is the prototypic example of an alkylating agent?
cyclophosphamide
55
what is the MOA of cyclophosphamide?
have reactive chemical groups that bind covalently toDNA causing disruption to shape of the alpha helix and cause the strand to break
56
if damaged DNA cannot be repaired, it triggers ___
cell death
57
t/f normal cells may be better at repairing damaged DNA than cancer cells
t
58
alkylating agents, like cyclophosphamide bind ____ (reversibly/irreversibly) to DNA
irreversibly
59
what are topoisomerases?
enzymes that unwind DNA strands that allow transcription to proceed smoothly
60
what do topoisomerase enzymes do?
introduce temporary strand breaks in the DNA strands to prevent tangling and supercoiling
61
what happens to the breaks caused by topoisomerases?
quicly repaired to maintain the structural integrity of th eDNA
62
what do topoisomerase inhibitors do?
stall the uncoiling process and halt DNA replication
63
____ is an example of an antibiotic isolated from bacteria that has anti-cancer activity
doxorubicin
64
what is doxorubicin?
natural product isolated from Step. speciies
65
doxorubicin is a ____ type antibiotic
anthracycline
66
anthracycline antibiotics like doxorubicin hava a unique ____- that gives them several cytotoxic effects
chemical structure
67
the ____ structure of the doxorubicin molecule wedges between the DNA strands and pushes them apart
flat ring structure
68
what happens if toposoimerase comes along to a strand of DNA that has been impacted by doxorubicin?
forma a static complex with the DNA molecule and the drug and prevents the progression of DNA replication, triggers cell death
69
doxorubicin forms ____ by its O2 containing groups
free radicals
70
what is the significance of doxorubicin forming free radicals?
causes additional DNA damage and cellular toxicity, causing death
71
what is a common ADR of doxorubicin that can limit its use?
cardiac toxicity
72
t/f it is not entirely clear of doxorubicin is more toxic to cardio cells compared to other cells
t
73
in order to make new DNA, cells must make more ____, the building blocks of DNA and RNA
nucleotides
74
___ and ___ precursors, using importnat components like ___ are assembled into nucleotides to be ready for incorporation into newly made DNA strands
purine and pyrimidine ; folate
75
____ are a subclass of antineoplastic drugs that interfere with the biosynthesis of nucleotides
antimetabolites
76
if DNA synthesis is halted due to the lack of available nucleotides, _____ pathways are initiated
cell death
77
when antimetabolites interfere with nucleotide synthesis, modified DNA and RNA may be made, but they wont make the proper ___
structures
78
dive an example of an antimetabolite used for cancer
methotrexate
79
methotrexate is structurally similar to ___
folate
80
methotrexate interacts with the ___ enzyme
dihydrofolate reductase
81
what is the function of methotrexate?
inhibits dihydrofolate reductase, reducing nucleotide and DNA synthesis
82
at low doses, methotrexate can be used for inflammatory conditions such as ___ to slow the proliferation of ____ cells
rheumatoid arthritis; immune
83
at higher doses, methotrexate reduces the proliferation of ____ cells
tumour
84
5-fluorouracil is an example of a _____ type drug
antimetabolite
85
the structure of 5-fluorouracil is structurally similar to ____ and ____ nucleotide bases
uracil and thiamine
86
5-flouraouracil's structure allows it to be ____ withinthe cell
metabolized
87
the 5-flourouracil metabolite, _____, inhibits thymidylate synthase, a critcal enzyme in the making of nucleotides
FdUMP
88
5-FU binds to ____, preventing further synthesis of thymidine nucleotides
thymidylate synthase
89
5-FU binds to TS ____ (irreversibly/reversibly)
irreversibly
90
what is the significance of 5-FU binding to TS?
prevents DNA from being made, starting cell death pathways
91
t/f antimetabolites interfere with the making of DNA precursors by having structural similarities with the endogenous substrates of the pathway
t
92
microtubules are critical structural components of ____
mitosis
93
what is the role of microtubles?
forming the mitotic spindles that organize the newly duplicated chromosomes and pull individual cells apart tp make daughter cells
94
microtubules consist of many ____ that dynamically assemble and disassemble to achieve the desired actions
tubulin dimers
95
interfering with the dynamic nature of microtubles can prevent ____
cellular division
96
what is vincristine?
a vinca alkaloid (another class of natural product compounds isolated from plants)
97
MOA of vincristine
prevents microtubule assembly and breaking down tubulin dimers, thus stopping cancer mitosis
98
what are taxanes?
class of antimicrotubule agents originally isolated from plants
99
give an example of a taxane
paciltaxel (taxol)
100
MOA of taxanes
prevents disassembly of microtubules, tubulin dimers still assemble, but there is no dynamic acticvity bc the disassembly is blocked
101
t/f the outcomes of vincristine and paclitaxela are the same, but the mechanisms are opposite
t
102
an ADR with antimicrotubule agents, especially with vincristine is the development of ____
neuropathies
103
what do antimicrotubules cause neuropathies?
due to impairing the important functions of microtubules in neurons
104
antimicrotubule agents are ___phase agents
M
105
antimetabolites are ___ phase agents
S
106
agents that act only during specific periods of cell cycle may be more effective in tumours that are ___ growing and less so in tumours that are ___ growing
fast; slow
107
t/f drugs like cyclophosphamide bind to DNA at any time and cause damage regardless of cell phase
t
108
cyclophosphamide and doxorubicin are classed as a ____agent
non-cell sycle specific
109
t/f oral mucositis is a common ADR of chemo
t
110
why does chemo lead to oral mucositis?
breakdown of protective barrier opens the door to infections (many concer pts are immunocomprosmised already)
111
what ca be used for oral mucositis?
oral rinses, topical anesthetics, saliva replaemnets, antibiotics
