Part 7: Cancer Treatments 1 Flashcards
define cancer
disease characterized by a defect in normal control mechanisms that govern cell survival, proliferation and differentiation
loss of ___ allows tumors to grow excessively and disrupt normal physiologic functions or organs and tissues
regulatory components
what are some cancer risks we cannot control?
age, sex, race, genetics
which sex is at higher risk of cancer
men, but women are close approaching
does the presence of certain genes or biomarkers that are linked to cancer mean that you will definitely develop cancer?
no
what are the most important determinants of cancer development?
environmental factors
what are the environmental factors that affect cancer development?
UV and radiation exposure, chemicals iin smoking tobacco
what virus has been shown to increase the risk of cervical cancer for women?
HPV
t/f lifesytle conditions like diet and exercise influence cancer risk
t
t/f cancer is the leading cause of death in canada
t
what are the 4 most common cancers in Canada?
- lung cancer
- breast cancer
- colorectal cancer
- Prostate cancer
t/f survival rates of cancer are increasing
t
t/f tumour cells originate from normal cells
t
how does cancer growth start?
chemical or physical carcinogen causes mutation
what happens in the “promotion” stage of cancer development?
cell division promoted by promoting and growth factors
t/f cancer initiators can also be promotors
t
an example of an initiator that can also be a promotor
cigarette smoke
do all cell mutations go on to daughter cells? why or why not?
no; because sometimes the cells can fix the mistake before or die before reproducing
t/f there can be multiple mutations within a population of cells
t
what happens in the “progression” stage of cancer development?
transformation to malignancy, further mutation and variability in the tumour
what does it mean when a tumour becomes malignant?
tumour has transformed so that its cellular process are no longer tightly controlled and regulated like normal cells
a hallmark of tumour biology is that the cells become invasive and take over ___
neighbouring tissues
what is stage 0 cancer?
early cancer, not detectable, stays at site of origin (in situ)
what are stages 1-3 cancer?
tumour is increasing in size and spread
what is stage 4 cancer?
tumour has invaded into other tissues and there is metastasis
what is contact inhibition?
in normal cells, when they come in contact with a neighbouring cell, they stop growing
do cancer cells have contact inhibitions?
no
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
at what stages are tumours typically detected?
2-3
why are tumours typically detected at stages 2-3?
onset of symptoms
in colon cancer, the invasion of the tumour across the colon membrane is likely to cause what detectable symptom?
blood in the stool
in what stage does a tumour have a rich blood and lymph supply?
stage 4
what are the common sites of secondary tumours that come off a stage 4 tumour?
areas that are highly perfused (liver, brain, lungs)
what are the 3 main ways to treat cancer?
- surgical removal
- radiation
- chemotherapy
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_
does radiation specifically target cancer cells ?
no
chemotherapy is also called ____ (3)
- antineoplastic drugs
- anticancer drug
- immunotherapy
what are antineoplastic drugs?
drugs that prevent the growth of abnormal cells (neoplasms)
how do antineoplatic drugs work to prevent abnormal cell grwth?
interfering with aspects of the cell cycle and preventing rapidly dividing cells from proliferating
there are some newer drugs that target tumour ___ or ____ that have been shown to be increased in cancer cells
biomarkers and cellular processes
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
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
what is a typical target of antineoplastic drugs?
quickly dividing cells
does the approach to target “rapidly dividing cells” spare all healthy cells?
no
t/f the max tolerable dose of anti-cancer medications should be used
true
t/f the chosen cancer treatment must be tolerable so the whole course of treatment can be completed
t
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
why is chemo typically given in cyclic rounds?
reduce ADR by allowing healthy tissues to repair themselves
many tumours are apprximated to follow a ____ growth pattern
exponential
what is the typical size of a tumour that can be detected?
1cm3, small green pea
what is reccurence of cancer?
after removal of cancer, some cells remain and start to grow new tumours
if chemo treatments are spaced too far apart, what can happen?
cancer cell #s increase too much
what are the 2 key processes of the cell cycle that allow proliferation of tumour cells?
- S phase (making copy of DNA
2. M phase (mitosis)
what is the prototypic example of an alkylating agent?
cyclophosphamide
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
if damaged DNA cannot be repaired, it triggers ___
cell death
t/f normal cells may be better at repairing damaged DNA than cancer cells
t
alkylating agents, like cyclophosphamide bind ____ (reversibly/irreversibly) to DNA
irreversibly
what are topoisomerases?
enzymes that unwind DNA strands that allow transcription to proceed smoothly
what do topoisomerase enzymes do?
introduce temporary strand breaks in the DNA strands to prevent tangling and supercoiling
what happens to the breaks caused by topoisomerases?
quicly repaired to maintain the structural integrity of th eDNA
what do topoisomerase inhibitors do?
stall the uncoiling process and halt DNA replication
____ is an example of an antibiotic isolated from bacteria that has anti-cancer activity
doxorubicin
what is doxorubicin?
natural product isolated from Step. speciies
doxorubicin is a ____ type antibiotic
anthracycline
anthracycline antibiotics like doxorubicin hava a unique ____- that gives them several cytotoxic effects
chemical structure
the ____ structure of the doxorubicin molecule wedges between the DNA strands and pushes them apart
flat ring structure
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
doxorubicin forms ____ by its O2 containing groups
free radicals
what is the significance of doxorubicin forming free radicals?
causes additional DNA damage and cellular toxicity, causing death
what is a common ADR of doxorubicin that can limit its use?
cardiac toxicity
t/f it is not entirely clear of doxorubicin is more toxic to cardio cells compared to other cells
t
in order to make new DNA, cells must make more ____, the building blocks of DNA and RNA
nucleotides
___ and ___ precursors, using importnat components like ___ are assembled into nucleotides to be ready for incorporation into newly made DNA strands
purine and pyrimidine ; folate
____ are a subclass of antineoplastic drugs that interfere with the biosynthesis of nucleotides
antimetabolites
if DNA synthesis is halted due to the lack of available nucleotides, _____ pathways are initiated
cell death
when antimetabolites interfere with nucleotide synthesis, modified DNA and RNA may be made, but they wont make the proper ___
structures
dive an example of an antimetabolite used for cancer
methotrexate
methotrexate is structurally similar to ___
folate
methotrexate interacts with the ___ enzyme
dihydrofolate reductase
what is the function of methotrexate?
inhibits dihydrofolate reductase, reducing nucleotide and DNA synthesis
at low doses, methotrexate can be used for inflammatory conditions such as ___ to slow the proliferation of ____ cells
rheumatoid arthritis; immune
at higher doses, methotrexate reduces the proliferation of ____ cells
tumour
5-fluorouracil is an example of a _____ type drug
antimetabolite
the structure of 5-fluorouracil is structurally similar to ____ and ____ nucleotide bases
uracil and thiamine
5-flouraouracil’s structure allows it to be ____ withinthe cell
metabolized
the 5-flourouracil metabolite, _____, inhibits thymidylate synthase, a critcal enzyme in the making of nucleotides
FdUMP
5-FU binds to ____, preventing further synthesis of thymidine nucleotides
thymidylate synthase
5-FU binds to TS ____ (irreversibly/reversibly)
irreversibly
what is the significance of 5-FU binding to TS?
prevents DNA from being made, starting cell death pathways
t/f antimetabolites interfere with the making of DNA precursors by having structural similarities with the endogenous substrates of the pathway
t
microtubules are critical structural components of ____
mitosis
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
microtubules consist of many ____ that dynamically assemble and disassemble to achieve the desired actions
tubulin dimers
interfering with the dynamic nature of microtubles can prevent ____
cellular division
what is vincristine?
a vinca alkaloid (another class of natural product compounds isolated from plants)
MOA of vincristine
prevents microtubule assembly and breaking down tubulin dimers, thus stopping cancer mitosis
what are taxanes?
class of antimicrotubule agents originally isolated from plants
give an example of a taxane
paciltaxel (taxol)
MOA of taxanes
prevents disassembly of microtubules, tubulin dimers still assemble, but there is no dynamic acticvity bc the disassembly is blocked
t/f the outcomes of vincristine and paclitaxela are the same, but the mechanisms are opposite
t
an ADR with antimicrotubule agents, especially with vincristine is the development of ____
neuropathies
what do antimicrotubules cause neuropathies?
due to impairing the important functions of microtubules in neurons
antimicrotubule agents are ___phase agents
M
antimetabolites are ___ phase agents
S
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
t/f drugs like cyclophosphamide bind to DNA at any time and cause damage regardless of cell phase
t
cyclophosphamide and doxorubicin are classed as a ____agent
non-cell sycle specific
t/f oral mucositis is a common ADR of chemo
t
why does chemo lead to oral mucositis?
breakdown of protective barrier opens the door to infections (many concer pts are immunocomprosmised already)
what ca be used for oral mucositis?
oral rinses, topical anesthetics, saliva replaemnets, antibiotics
