Cancer Chemotherapy Flashcards by Iseoluwa Ojo

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

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Cancer is one of the major causes of death in the developed nations

T/F

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One in ________ people will be diagnosed with cancer during their lifetime

three

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Cancer is also responsible for approximately ______ of all deaths in the UK

1⁄4

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_____ and _____ cancer comprises the largest category, closely followed by _____ and _______ cancer

lung and bowel

breast and prostate

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Malignant tumours are distinguished by their capacity for __________ , their __________ and their ability to __________

de-differentiation

invasiveness

metastasise

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There are three main approaches to treating established cancer:
 __________
 __________
 __________

 Surgical excision
 Irradiation
 Chemotherapy

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Cancer cells manifest to varying degrees. Four characteristics distinguish them from normal cells:

¤ Uncontrolled ____________
¤ ____________
¤ ____________
¤ ____________

¤ Uncontrolled proliferation
¤ Differentiation
¤ Invasiveness
¤ Metastasis

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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

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Genesis of a Cancer cell

The activation of __________ to __________.

proto-oncogenes to oncogenes.

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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

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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

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Loss of function of tumour suppressor genes can be the critical event in carcinogenesis

T/F

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A major difficulty in treating cancer is that tumour growth is usually __________ before cancer is diagnosed

far advanced

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Doubling time of tumour cells varies from ________ (___________) to ________ (______) to ______ (__________ cancer)

24 hours (Burkitt’s lymphoma)

2 weeks (leukaemia)

3 months (mammary cancer)

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____ doublings will be required to produce a cell mass of ___ cm (containing ___ cells)

10^9

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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

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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 ______________

not constitute a problem

cancer chemotherapy difficult

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Cytotoxic drugs affect only the _______ of cancer cells but no inhibitory effect on _______,_______, or _________

cell division

invasiveness, differentiation or metastasis

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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

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Cytotoxic drugs may have the following adverse effects

Depression of ______ in children
________
_____________
They can be ________ (_______ Malignancies)

growth

Sterility

Teratogenicity

carcinogenic ; Secondary

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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

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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

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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

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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 1. 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 1. 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

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