Cancer Chemotherapy Flashcards
Cancer is a disease characterized by (controlled or uncontrolled?) and spread of (normal or abnormal?) forms of the body’s own cells
uncontrolled
multiplication
abnormal
Cancer is one of the major causes of death in the developed nations
T/F
T
One in ________ people will be diagnosed with cancer during their lifetime
three
Cancer is also responsible for approximately ______ of all deaths in the UK
1⁄4
_____ and _____ cancer comprises the largest category, closely followed by _____ and _______ cancer
lung and bowel
breast and prostate
Malignant tumours are distinguished by their capacity for __________ , their __________ and their ability to __________
de-differentiation
invasiveness
metastasise
There are three main approaches to treating established cancer:
__________
__________
__________
Surgical excision
Irradiation
Chemotherapy
Cancer cells manifest to varying degrees. Four characteristics distinguish them from normal cells:
¤ Uncontrolled ____________
¤ ____________
¤ ____________
¤ ____________
¤ Uncontrolled proliferation
¤ Differentiation
¤ Invasiveness
¤ Metastasis
Genesis of a Cancer cell
A normal cell turns into a cancer cell because of one or more ______ in its DNA, which can be ______ or __________
mutation
acquired or inherited
Genesis of a Cancer cell
The activation of __________ to __________.
proto-oncogenes to oncogenes.
Proto-oncogenes, which are genes that normally control ________, ________ and ________ may be converted to ________ that induce ________ change by ________ or ________ action
cell division
apoptosis ; differentiation
oncogenes; malignant
viral ; carcinogenic action
Genesis of a Cancer cell
The inactivation of __________ genes: Normal cells contain genes that can _______ malignant change- termed __________ genes (__________)
tumour suppressor genes
suppress ; tumour suppressor genes
antioncogenes
Loss of function of tumour suppressor genes can be the critical event in carcinogenesis
T/F
T
A major difficulty in treating cancer is that tumour growth is usually __________ before cancer is diagnosed
far advanced
Doubling time of tumour cells varies from ________ (___________) to ________ (______) to ______ (__________ cancer)
24 hours (Burkitt’s lymphoma)
2 weeks (leukaemia)
3 months (mammary cancer)
____ doublings will be required to produce a cell mass of ___ cm (containing ___ cells)
30
2
10^9
The cells of a solid tumour can be considered as belonging to three compartments:
- Compartment A: Consists of ________ cells, possibly being ___________________________
- Compartment B consists of _____\ cells (___ phase), which ______________________
- Compartment C consists of cells that are ________________ but which contribute to the ______________
dividing cells; continuously in cell cycle
resting cells ; Go phase ; not dividing, are potentially able to do so
no longer able to divide; tumour volume
Only the ____% of cells in compartment A are susceptible to cytotoxic drugs, the cells in compartment C do __________ while the cells in compartment B make ______________
5
not constitute a problem
cancer chemotherapy difficult
Cytotoxic drugs affect only the _______ of cancer cells but no inhibitory effect on _______,_______, or _________
cell division
invasiveness, differentiation or metastasis
Cytotoxic drugs may have the following adverse effects
__________ toxicity (______suppression) Impaired ___________
Loss of _____ (_____)
Damage of __________ epithelium (Mucositis)
Bone marrow (myelosuppression)
wound healing
hair (alopecia)
gastrointestinal
Cytotoxic drugs may have the following adverse effects
Depression of ______ in children
________
_____________
They can be ________ (_______ Malignancies)
growth
Sterility
Teratogenicity
carcinogenic ; Secondary
Special Characteristics of Cancer Cells
A. Uncontrolled Proliferation
Changes that lead to the uncontrolled proliferation of tumour cells are:
Inactivation of _________ genes Transformation of ________ into ________
tumour suppressor genes
proto-oncogenes into oncogenes
Special Characteristics of Cancer Cells
A. Uncontrolled Proliferation
Uncontrolled proliferation can also occur as a result of changes in several cellular systems
1)Growth factors- ______ and ______ pathways
2) Cell cycle transducers e.g .______, _________ kinase of cyclin dependent ________
3)________ machinery that normally disposes of abnormal cells
4) ___________ expression
5) Local blood vessels- tumour directed _________
receptors and signalling
cyclins, cyclin dependent; inhibitors
Apoptotic; Telomerase
angiogenesis
Special Characteristics of Cancer Cells
Uncontrolled proliferation:
Apoptosis: Programmed cell death and genetic mutations in the ________ genes.
__________ is a hallmark of cancer.
Inactivation of _________ factors or activation of _________ factors
anti-apoptotic
Resistance to apoptosis
anti-apoptotic
Special Characteristics of Cancer Cells
Uncontrolled proliferation:
Telomerase expression: Telomere are specialized structures that _____________________________, ______ them from _________,___________, and __________ with other chromosomes
cap the ends of chromosomes
protecting
degradation, re-arrangement and fusion
Special Characteristics of Cancer Cells
Uncontrolled proliferation:
- control of tumour related blood vessels: this factor influences ________ due to development of _____________
total tumour mass
its own blood supply
Special Characteristics of Cancer Cells
B. Differentiation and loss of function
Division of undifferentiated stem cells giving rise to _____ cells which also differentiate to become ______ cells
daughter
mature cells
Special Characteristics of Cancer Cells
B. Differentiation and loss of function
Example: fibroblasts secrete and organize ____________
extracellular matrix
Special Characteristics of Cancer Cells
B. Differentiation and loss of function
Poorly differentiated cancers multiply (slower or faster?) and carry (better or worse?) prognosis than well differentiated
cancers
Faster
Worse
Special Characteristics of Cancer Cells
C. Invasiveness
Ability of cancer cells to ______________
move around the system
Special Characteristics of Cancer Cells
C. Invasiveness
Cancer cells secrete ________ that break down the ___________, enabling them to move around
metalloproteinases
extra cellular matrix
Special Characteristics of Cancer Cells
D. Metastases
Formation of ________ tumours by cells that are released from the initial or primary tumour and reach other sites through ______________
secondary tumours
blood vessels
_________ are the principal cause of mortality and morbidity in most cancers and constitute major problems in cancer therapy
Metastases
Metastases of mammary cancer are often found in ______,________ and ______
lungs, bones and brain
Classification of cancer drugs
A
_______ agents
Anti______
_____ products
__________ and ________
Miscellaneous
Alkylating agents
Antimetabolites
Natural products
Hormones and antagonists
Miscellaneous
Classification of drugs
A
Alkylating agents: ________,________,______,________,__________ , methylhydrazine derivatives, alkyl sulfonate, nitroso ureas, triazenes, platinium co-ordination complexes
Cyclophosphamide, chlorambucil, nitrogen mustard, ethylene imines, methylmelamines
Classification of drugs
A
Antimetabolites: _______ analogues ( ————- ), ________ analogues (______________ ), _______ analogue (________) and related metabolites
Folic acid; methotrexate
pyrimidine; 5 fluorouracil
purine; mercaptopurine
Classification of drugs
A
Natural products: ________ alkaloids (_______,_______), _______,____________,__________
Vinca alkaloids
vinblastine, vincristine
taxanes, camptothecins, antibiotics
Classification of drugs
A
Hormones and antagonists:________,_________,________, _______
Estrogens, progestins, androgens, adrenocorticosteroids
Classification of drugs
A
Miscellaneous:__________
inhibitors, -__________ modifiers
Protein tyrosine kinase
biological response
Classification of drugs
B
Action on particular phases on the cell
cycle
- Phase-specific agents e.g. _____ alkaloids act in __________;
cytarabine, hydroxycarbamide,
fluorouracil, methotrexate and
mercaptopurine act in _____-phase
vinca ; mitosis
S
Classification of drugs
B
Action on particular phases on the cell
cycle
_______-_______ agents
_______ _______ agent
_______ _______ agents
Phase-specific agents
Cycle specific agent
Cycle non-specific agents
Classification of drugs
B
Action on particular phases on the cell
cycle
Cycle specific agents- act at ____ stages of the cell cycle but _________________
e.g. _______ agents; _______,________,_______
all
do not have much effect on cells out of cycle
alkylating
Dactinomycin; Doxorubicin; Cisplatin
Classification of drugs
B
Action on particular phases on the cell
cycle
Cycle non-specific agents: these act on cells _______________________
e.g. _______ and ________
whether in cycle or not
bleomycin and nitroso ureas
Phase non-specific drugs
_______ drugs
____________
_______ antibiotics
_______
___________
___________
Alkylating drugs
Nitrosoureas
Antitumor antibiotics
Cisplatin
Decarbazine
Procarbazine
ALKYLATING AGENTS
Forms __________ bonds with cell substituents
Cause excision of __________ and __________
Covalent
guanine and chain breakage
Alkylating agents
Principal effect occurs during ________ and the resulting ______ triggers ______
Alkylating agents contain chemical groups that can form ____________ with particular _______ substances in the cell
DNA synthesis ; damage
apoptosis; covalent bonds
nucleophilic
Alkylating Agents
Alkyl agents form carbon atom with _____ reactive and unstable electrons and thus reacts with ______,______, or ______ group
They interfere with both _______ and _______ which is the critical effect of anticancer alkylating agents
six
amine, hydroxyl or sulfhydryl group
transcription and replication
Alkylating Agents
The main impact is seen during ________ (____- phase) when some zones of the DNA are (paired or unpaired?) and more susceptible to ————-
This results in a block at _____ and subsequent _________
replication (S- phase)
unpaired ; alkylation
G2 ; apoptotic cell death
Alkylating Agents
All alkylating agents depress ________ function and cause _____ disturbances
Other effects are depression of _______ (men), increased risk of ___________ leukaemia and other malignancies
bone marrow function; GIT disturbances
gametogenesis (men)
acute non-lymphocytic
Alkylating Agents
- Nitrogen Mustards
Related to???
It is inactive until metabolized in the liver by P450 ____________________
Have pronounced effect on _______
Can also be used as _________ given by oral, i.m and i.v routes
mustard gas
mixed function oxidases
lymphocytes
immunosuppressants
Most commonly used alkylating agent is??
Cyclophosphamide
Side effects of cyclophosphamide are: _________ depression, vomiting, nausea, haemorrhagic ______
bone marrow
cystitis
Other examples of nitrogen mustards are:
__________
_________
___________
__________\
Chlorambucil
Ifosfamide
Melphalam
Estramustine
Estramustine- combination of _______(_______) and _________.
This has both ______ and _______ action.
Used in _______ cancer
chlormethine (mustine) and oestrogen
cytotoxic and hormonal
prostate
Alkylating Agents: Nitrosoureas
Lipid (soluble or insoluble ?) and (can or can not ?) cross the blood brain barrier
Used against tumours of the ______ and _______
Have pronounced depressive effect on _______
Examples are _______ and _______
soluble; can
brain and meninges
bone marrow
lomustine and carmustine
Alkylating Agents: Busulfan
Has _______ effect on bone marrow
Depressed formation of _____ and _______ in low dosage and _______ in higher dosage
Used in chronic granulocytic leukemia
selective
granulocytes and platelets
red blood cells
PLATINUM COMPOUNDS
Cisplatin: _____ soluble surrounded by __________ atoms and ________ groups.
It’s action is analogous to ________
Water
two chlorine atoms
two ammonia group
Alkylating agents
Platinum compounds: Cisplatin
When it enters the cell, ____ dissociates leaving a __________ that reacts with ——- and then interacts with _____
This causes _______ of DNA
Cl-
reactive complex
water; DNA
denaturation
Platinum compounds : cisplatin
Cisplatin is used in _____________ tumours
ovary and testes
PLATINUM COMPOUNDS: Cisplatin
Given by I.V route or by infusion
It is highly ____toxic. Strict regime of ______ and ____- should be instituted
Nausea, vomiting, tinnitus, _____ loss, peripheral _______, hyper_______ and _______- reactions may occur
nephro
hydration and diuresis
hearing; neuropathies; uricaemia
anaphylactic
Platinum Compounds: Carboplatin
Derivative of _______
Has (more or less?) nephrotoxic, neurotoxic, ototoxic, nauseating and vomiting effects than cisplatin
cisplatin
Less
Platinum Compounds: Oxaliplatin
Platinum containing compound with ________
restricted application
Platinum Compound: Dacarbazine
Activated in the liver and the resulting compound is subsequently cleared in the target cell to release an alkylating derivative
Unwanted effects include ______toxicity, severe nausea and vomiting
myelo
Dacarbazine is a Prodrug
T/F
T
Platinum Compounds: Temozolomide
related compound with a ______ usage (malignant ———-)
restricted
glioma
Platinum compounds
_____platin
____platin
____platin
_________
__________
Cisplatin
Carboplatin
Oxaliplatin
Dacarbazine
Temozolomide
ANTIMETABOLITES: Folate Antagonists
Methotrexate
Folates are essential for synthesis of _________ and ____ which are essential for _________ and cell division
Folate antagonists interfere with ——— synthesis
purine nucleotides and thymidylate
DNA synthesis
thymidylate
Folate antagonists
Pharmacokinetics:
Given orally and also I.M, I.V or intrathecally
(Low or High?) lipid solubility thus poorly cross BBB
Metabolized into _________ derivatives
which are retained in the cell for ______ or _____
Low
polyglutamate
weeks or months
Antimetabolites: Pyrimidine analogues
Fluorouracil
Analogue of ———-
Interferes with ________ synthesis
Converted to ________
Inhibits dna, rna, or protein synthesis
Given parenterally
uracil
2’- deoxythymidylate (DTMP)
fluorodeoxyuridine monophosphate (FDUMP)
Antimetabolites
_______
_________
__________
_____________
________________
Raltitrexed
Pemetrexed
Capecitabine
Cytarabine
Gemcitabine
Antimetabolites
Raltitrexed: Inhibits ____________
Pemetrexed: Inhibits _______________
Capecitabine: Metabolized to ______
Cytarabine:
Analogue of naturally occurring _______
thymidylate synthetase
thymidylate transferase
fluorouracil
2’- deoxycytidine
Cytarabine:
Undergoes ______ reaction to give _____________________
phosphorylation
cytosine arabinoside triphosphate
Gemcitabine
New analogue of __________
Given in combination with other drugs such as ________
cytarabine
cisplatin
Antimetabolites: Purine analogues
Main examples are_________,__________,__________,__________ and _________
fludarabine, pentostatin, cladribine, mercaptopurine and tioguanine
Antimetabolites: Purine analogues
Action interferes with critical pathways in purine metabolism and can have significant effects on cell proliferation
_______,________, and _______ are used mainly in the treatment of ______
Cladribine, mercaptopurine and tioguanine
leukemia
CYTOTOXIC ANTIBIOTICS
Act through ___________________
Anthracyclines
Examples:
_____,________,_________,________,_________ and __________
direct action on DNA
Doxorubicin, idarubicin, daunorubicin, epirubicin, aclarubicin and mitoxantrone
CYTOTOXIC ANTIBIOTICS
Anthracyclines
Doxorubicin binds to ____ and inhibits ___________________________
Has a direct action on __________ (a DNA
gyrase
DNA
both DNA and RNA synthesis
topoisomerase II
CYTOTOXIC ANTIBIOTICS
Anthracyclines
The activity is markedly increased in _______ cells
Doxorubicin is given by I.V infusion
Causes cumulative, dose-related ______ damage leading to _______ and _______
Action may be the result of generation of _______ _______
proliferating
cardiac damage; dysrhythmias
heart failure; free radicals
CYTOTOXIC ANTIBIOTICS :Dactinomycin
Intercalates in the _______ of DNA between adjacent ___________ pairs, interfering with the movement of ____________ along the gene and thus preventing transcription
Has similar action as anthracyclines on __________
Has no ________toxic effect
Mainly used in the treatment of ______ cancers
minor groove
guanosine-cytosine ; RNA polymerase
topoisomerase II
cardiotoxic
pediatric cancers
CYTOTOXIC ANTIBIOTICS: Bleomycins
Group of ___________ glycopeptide antibiotics that ____________________, causing chain ______ and release of ______ leading to generation of ______
Most effective in ____ phase of the cell cycle and mitosis but also active against _______ cells (___ phase)
Used to treat _____ cancer
metal-chelating
degrade preformed DNA
fragmentation ; free bases
superoxide; G2; non-dividing cells
Go phase; germ line cancer
CYTOTOXIC ANTIBIOTICS: Mitomycin
Functions as a _________ alkylating agent
Binding preferentially at ____ of the ______ nucleus
_______ DNA and may also ______ DNA through the generation of _______
bifunctional ; O6
guanine nucleus; Cross-link
degrade DNA ; free radicals
CYTOTOXIC ANTIBIOTICS: procarbazine
Inhibits DNA and RNA synthesis and interferes with mitosis at ____
Given orally
Mainly used in ______
Causes ______-like actions with alcohol
Exacerbates the effects of ________
interphase
Hodgkin’s disease
disulfiram; CNS depressants
CYTOTOXIC ANTIBIOTICS: Hydroxycarbamide
Aka ____________
-A ______ analogue that inhibits ________, thus interfering with the conversion of _________ to ________
hydroxyurea
Urea; ribonucleotide reductase
ribonucleotides to deoxyribonucleotides
PLANT DERIVATIVES: Vinca Alkaloids
Derived from ____________
Examples are _______,_______, and _______
Vinorelbine is a semi-synthetic vinca alkaloid with similar properties that is mainly used in ______ cancer
Only effective at _____ stage (mitosis)
Madagascar periwinkle
vincristine, vinblastine and vindesine
breast cancer
mitotic stage (mitosis)
PLANT DERIVATIVES: Vinca Alkaloids
Binds to ______ and inhibits its _______ into ________, preventing _______ formation in ______ cells and causing arrest of __________
Inhibits other cellular activities that involve the ______ such as _______ and ________ as well as _________ in neurones
They are relatively (toxic or non-toxic?)
There could be (reversible or irreversible ?) alopecia
tubulin ; polymerization
microtubules ; spindle
dividing cells ;metaphase
microtubules ; phagocytosis
chemotaxis ; axonal transport
non-toxic; reversible alopecia
PLANT DERIVATIVES: TAXANES
______ and ________ are derived from a naturally occurring compound found in the _____ of the ______ tree
Acts on ________, by ________ them
in the _________ stage achieving
similar effects as __________
Given by I.V infusion
Paclitaxel and docetaxel
bark; yew tree
microtubules; stabilizing
polymerase; vinca alkaloids
PLANT DERIVATIVES: TAXANES
Used in the treatment of _______ cancer
_______ plus __________ are choice in the treatment of _______ cancer
breast cancer
Paclitaxel ; carboplasmin
ovarian
PLANT DERIVATIVES : Etoposide
Derived from_________
Acts by inhibiting _______ function and _______ transport
Also have effect on _______ similar to that seen with _________
Mandrake root
mitochondrial ; nucleoside transport
topoisomerase II ; doxorubicin
PLANT DERIVATIVES: Camptothecins
________ and. _______ isolated from the ____ of the tree __________________—
Binds to and inhibits _________
High levels occur _______
Irinotecan and topotecan
stem; Camptotheca acuminata
topoisomerase II
Hormones
Tumors derived from hormone sensitive tissues may be ______________, an effect related to the presence of ——— receptors in the malignant cells
Their growth can be inhibited by hormones with _______ actions, by hormone antagonists or by agents that inhibit the endogenous hormone synthesis
hormone dependent
steroid; opposing
Hormones or their analogues that have _______ actions on target tissues can be used in the treatment of tumors of those tissues
inhibitory
HORNONES: Glucocorticoids
e.g. __________ and __________
Have marked __________ effects on lymphocyte __________ and used in the treatment of __________ and __________
Prednislone and dexamethasone
inhibitory ; proliferation
leukemia and lymphomas
HORNONES: Progestogens
e.g. give me 3 ________,________,________
Used in _______ neoplasms and in ______ tumors
Megestrol, norehisterone and medroxyprogesterone
endometrial; renal
HORMONES: Oestrogens
Eg_____________ and ______________
Oestrogens are used clinically in the
________ treatement of androgen- dependent _______ tumours
Could also be treated with _________ hormone analogues
Diethylstilbesterol and ethinyloestradiol
palliative; prostatic
gonadotrophin-releasing
HORMONE ANTAGONISTS
: Anti-oestrogense.g. ______
Effective in hormone-dependent ______ cancer and may have a role in preventing this cancer
It competes with _______ for the oestrogen receptors and inhibits the transcription of ________-
Tamoxifen has __________
effects
Tamoxifen
breast; endogenous oestrogens
oestrogen
cardio-protective
HORMONE ANTAGONISTS
: Anti-oestrogens
Other examples are ______,______,_______,________,________ and _______
Toremifen,
fulvestrant, anastrozole, letrozole,
exemestane and aminoglutethimide
HORMONE ANTAGONISTS: Anti-androgens
Eg _________,________, and ————
Used for ______ cancer
Flutamide, cyproterone and
bicalutamide
prostate
RADIOACTIVE ISOTOPES
Radioactive iodine used in the treatment of ________ tumors
thyroid
MISCELLANEOUS AGENTS
E.G. list 5
Crisantaspase, amsacrine, monoclonal antibodies, imatinib mesylate, biological response modifiers
MISCELLANEOUS AGENTS
Monoclonal Antibodies
Immunoglobulins e.g. ______ and ______
rituximab and trastuzumab
MISCELLANEOUS AGENTS
Alemtuzumab
Lyses ———-
Used in treatment of resistant ______________
B-lymphocytes
chronic
lymphocytic leukemia
RESISTANCE TO ANTICANCER DRUGS
Decreased accumulation of cytotoxic drugs in cells. E.g. ________,________,______
decrease in the amount of drug taken up by the cell e.g. _________
Insufficient activation of the drug (e,g,
___________,_________, and ————)
doxorubicin, vinblastine and dactinomycin
methotrexate
mercaptopurine, fluorouracil and
cytarabine
RESISTANCE TO ANTICANCER DRUGS
Increase in inactivation e.g. ______ and ———
Increased concentration of target enzymes e.g. _______
Decreased requirement for substrate e.g. __________
Increased utilization of alternative metabolic pathways e.g. _________
mercaptopurine and cytarabine
methotrexate
crisantaspase
antimetabolites
RESISTANCE TO ANTICANCER DRUGS
Rapid repair of drug-induced lesions e.g. ________
Altered activity of target (modified topoisomerase II e.g. _______)
Mutation e.g. p53 gene and over expression of Bcl-2 gene family (________)
alkylating agents
doxorubicin
cytotoxic drugs
MISCELLANEOUS AGENTS
Biological response modifiers
Agents that ___________ are biological response modifiers
E.g. _______,________ (recombinant interleukin 2) and _______ (form of vitamin A)
enhance the host’s response
Interferon α
aldesleukin
Tretinoin
