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Genetics
-________ cause cells to become malignant in several ways
-________ are normal genes that are involved in the controlled growth, division and death (________) of cells
-An oncogene is a mutation in a ________.
-An abnormal oncogene can effect cell growth control proteins & trigger ________ cell division.
Genetics
- -Genes cause cells to become malignant in several ways
- -Protooncogenes are normal genes that are involved in the controlled growth, division and death (apoptosis) of cells
- -An oncogene is a mutation in a protooncogene.
- -An abnormal oncogene can effect cell growth control proteins & trigger unregulated cell division.
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Genetics
-Tumor suppressor genes (________) signal a cell to cease multiplying and act to stop the action of ________.
-If the tumor suppressor genes become lost or dysfunctional cells can reproduce________.
-Other genes repair ________ damage.
-If these are damages, mutations are not repaired and passed to the next ________ or daughter cells.
Genetics
- -Tumor suppressor genes (antioncogenes) signal a cell to cease multiplying and act to stop the action of oncogenes.
- -If the tumor suppressor genes become lost or dysfunctional cells can reproduce uncontrollably.
- -Other genes repair DNA damage.
- -If these are damages, mutations are not repaired and passed to the next generation or daughter cells.
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Genetics
-Since it takes time for enough cell mutation to occur and cancer is more likely to occur in ________ individuals.
Genetics
-Since it takes time for enough cell mutation to occur and cancer is more likely to occur in older individuals.
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Cell cycle & Chem
-Chemo causes cell ________ by interfering with cell ________
-Cell cycle non-specific (CCNS) drugs act during ________ phase of the cell cycle.
-Cell cycle specific (CCS) drugs act during a _______ phase of the cell cycle.
-________ are more effective against rapidly growing cancer cells.
Cell cycle & Chem
- -Chemo causes cell death by interfering with cell replication
- -Cell cycle non-specific (CCNS) drugs act during any phase of the cell cycle.
- -Cell cycle specific (CCS) drugs act during a specific phase of the cell cycle.
- -CCS are more effective against rapidly growing cancer cells.
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Drugs
-________
-________ agents (Some are CCS)
-________antibiotics
-________
-________
-Anti________
-________ inhibitors
Drugs
- -CCNS
- -Alkylating agents (Some are CCS)
- -Anti-tumor antibiotics
- -Hormones
- -CCS-Antimetabolites
- -Mitotic inhibitors
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Growth Fraction & Doubling Time
-________ factors that play a major role in response of cancer to chemo
-Growth ________is the number of cells proliferating within the tumor
-________ is more effective against cells that have a high growth fraction
-Small and early cancer cells and fast-growing tumors respond well to ________ with a ________ cure rate.
Growth Fraction & Doubling Time
- -Two factors that play a major role in response of cancer to chemo
- -Growth fraction is the number of cells proliferating within the tumor
- -Chemo is more effective against cells that have a high growth fraction
- -Small and early cancer cells and fast-growing tumors respond well to chemo with a higher cure rate.
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Growth & Chemo
-Growth is usually faster in ________ stages of tumor development
-As tumor grows that blood supply ________-> ________ growth rate
-Chemo is moat effect in ________ tumors with sufficient ________ supply.
-As tumor enlarges its growth fraction ________ and doubling time________--> ________ effectiveness of chem
Growth & Chemo
- -Growth is usually faster in early stages of tumor development
- -As tumor grows that blood supply decrease-> slower growth rate
- -Chemo is moat effect in young tumors with sufficient blood supply.
- -As tumor enlarges its growth fraction decrease and doubling time increase--> decreased effectiveness of chem
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Chemo
-Non-selective so both ________ & ________cells are affected
-Side effects are mostly related to toxic effects on ________ cells
-Chemo is effective because healthy cells repair ________ and continue to ________.
-So, side effects of chemo are generally ________.
Chemo
- -Non-selective so both healthy & malignant cells are affected
- -Side effects are mostly related to toxic effects on normal cells
- -Chemo is effective because healthy cells repair themselves and continue to grow.
- -So, side effects of chemo are generally temporary.
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Types of Therapy
-Adjuvant therapy?
-Neo-adjuvant therapy?
-Palliative therapy?
Types of Therapy
- -Adjuvant therapy-used after another tx
- -Neo-adjuvant therapy-used first to shrink tumor so it can be removed by surgery
- -Palliative therapy-used to relieve symptoms associated with advanced disease
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Protocols
-Chemo administration is guided by specific ________ that were developed based on the results of controlled ________ studies.
-The length of treatment is determined by type of ________, extent of ________, type of ________, excepted ________ effects of the drugs.
-Usually given in ________ to increase chance of ________ cells and allowing normal ones to ________.
Protocols
- -Chemo administration is guided by specific protocols that were developed based on the results of controlled research studies.
- -The length of treatment is determined by type of chemo, extent of malignancy, type of chemo, excepted side effects of the drugs.
- -Usually given in cycles to increase chance of killing cells and allowing normal ones to recover.
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Protocols
-The ________, ________and ________ of cycles of chemo are based upon ________ & ________ of tumor , whether disease has metastasized and the condition of the patient.
-________ may consist of one drug or combination
-Duration of each treatment varies from________ to ________ and may be repeated weekly, biweekly, or monthly.
Protocols
- -The duration, frequency and number of cycles of chemo are based upon types & size of tumor , whether disease has metastasized and the condition of the patient.
- -Chemo may consist of one drug or combination
- -Duration of each treatment varies from minutes to days and may be repeated weekly, biweekly, or monthly.
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New Developments & Protocols
-________ chemo protocols have been used mostly recently
-The interval between successive dose of chemo is ________ which has--> improved ________
New Developments & Protocols
- -Dose dense chemo protocols have been used mostly recently
- -The interval between successive dose of chemo is shortened which has--> improved survival
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Drug Resistance
-Malignant tumors can develop resistance to ________
-Multidrug resistance (________) can occur for several reasons:
-1. drug may not kill ________& cells may ________ & become resistance.
-2.________ resistance of some tumor cells.
Drug Resistance
- -Malignant tumors can develop resistance to chemo
- -Multidrug resistance (MDR) can occur for several reasons:
- -1. drug may not kill cells & cells may mutate & become resistance.
- -2. natural resistance of some tumor cells.
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Combo Chemo
-Combinations of chemo have consistently shown to be more effective than ________ therapy
-Chemo is most effective when it kills cells in ________ phases of the cell cycles.
-Combo therapy makes this more likely to occur.
-________ & ________ are often combined
-Each drug should have a different mode of ________ & different dose-limiting________.
Combo Chemo
- -Combinations of chemo have consistently shown to be more effective than monodrug therapy
- -Chemo is most effective when it kills cells in all phases of the cell cycles.
- -Combo therapy makes this more likely to occur.
- -CCS & CCNS are often combined
- -Each drug should have a different mode of action & different dose-limiting toxicities.
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General Adverse Reactions to Chemo
-1. ________ suppression:
-________, ________,________
- 2. ________
-Anorexia, N&V, diarrhea, ________
-3. ________
-4. ________
-5. ________
General Adverse Reactions to Chemo
- -1. Bone marrow suppression:
- -Anemia, neutropenia, thrombocytopenia
- - 2. GI
- -Anorexia, N&V, diarrhea, mucoitis
- -3. Alopecia
- -4. Fatigue
- -5. Infertility
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Activities of Chemotherapy
-Chemo works on the principles of first order _________. That is, the number of tumor cells _________ is proportionate to the _________ administered.
-The number of cells_________ is a constant percent of the total number of cancer cells _________
-Examples: If there are 10 malignant cells present and the drug kills 80 percent of the cells then with the first dose, 8 will be killed. 80% of the remaining cells can be excepted to be killed with the second dose. However, the cells are _________during the process.
Activities of Chemotherapy
- -Chemo works on the principles of first order kinetics. That is, the number of tumor cells killed is proportionate to the dose administered.
- -The number of cells killed is a constant percent of the total number of cancer cells present.
- -Examples: If there are 10 malignant cells present and the drug kills 80 percent of the cells then with the first dose, 8 will be killed. 80% of the remaining cells can be excepted to be killed with the second dose. However, the cells are reproducing during the process.
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Chemotherapy
-Chemo is most effective against cells with a fast ________ rate and ________
- ________ cells, ____ cells and ________ cells have growth rates equal to most cancer cells.
-Most chemo has some degree of ________ to those cells.
-Major toxicity is ________ or ________ supression
-> anemia, leukopenia and thrombocytopenia
-The ________ (height of suppression ) takes about __-___weeks to develop
-To limit toxicities the drugs are given in a ________ allowing ________ in between doses.
Chemotherapy
- -Chemo is most effective against cells with a fast metabolic rate and reproduction
- -Bone marrow cells, GI cells and skin cells have growth rates equal to most cancer cells.
- -Most chemo has some degree of toxicity to those cells.
- -Major toxicity is myelosupression or bone marrow supression -> anemia, leukopenia and thrombocytopenia
- -The nadir (height of suppression ) takes about 1-2 weeks to develop
- -To limit toxicities the drugs are given in a series allowing recovery in between doses.
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Alkylating Agents
-________-kills cells in various & multiple stages of the cell cycle
-Most effective in ________ (________ phase)
-Several classifications in the group:
-1. Mustard gas derivatives (________)
-2. Nitrosureas (________)
-3. Alkyl sulfonates (________)
-4. Alkylating like drugs (________)
Alkylating Agents
- -CCNS-kills cells in various & multiple stages of the cell cycle
- -Most effective in G0 (resting phase)
- -Several classifications in the group:
- -1. Mustard gas derivatives (Cytoxan)
- -2. Nitrosureas (carmustine)
- -3. Alkyl sulfonates (Myleran)
- -4. Alkylating like drugs (cisplatin)
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Cytoxan
-Major problem is that Cytoxan is a severe _________ that can cause tissue _________
-Must be given through patent _________ line if given _______
-Patient must be well hydrated to prevent hemorrhage _________
-MESNA is a _________ often given with high dose _________ to inactivate urotoxic metabolites in bladder to minimize injury-_________ suppression &_________ are common.
Cytoxan
- -Major problem is that Cytoxan is a severe vesicant that can cause tissue necrosis
- -Must be given through patent IV line if given IV
- -Patient must be well hydrated to prevent hemorrhage cystitis
- -MESNA is a cytoprotectant often given with high dose cytocan to inactivate urotoxic metabolites in bladder to minimize injury
- -Bone marrow suppression & alopecia are common.
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Dealing with Extravastion
-The urea usually becomes _________ and _________ may occur
-If leakage of dug is obvious, prompt infiltration of the area with sterile _________ sodium _________ and application of an _________ compress for ___to_____ hours may minimize the local reaction
Dealing with Extravastion
- -The urea usually becomes indurated and sloughing may occur
- -If leakage of dug is obvious, prompt infiltration of the area with sterile isotonic sodium thiosulfate and application of an ice compress for 6 to 12 hours may minimize the local reaction
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Cytoxan & Herbs
-Avoid: Garlic ( _________), ginkgo (__________________), echinacea (_________), ginseng (_________), St. John's Wort (_________), kava kava (_________)
Cytoxan & Herbs
-Avoid: Garlic ( antiplatelet), ginkgo (increased antiplatelet activity), echinacea (decreased effect of immunosuppressive drugs), ginseng (alters bleeding time), St. John's Wort (interferes with chemo), kava kava (increased risk of bleeding)
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Antimetabolites
-Resemble natural metabolites which_________, _________ and _________ organic compounds for use by the body.
-Antimetabolites disrupt _________ processes and can inhibit _________ synthesis
-Classified as _________ and work during the _________ phase (_________ sythesis & metabolism) of cycle.
Antimetabolites
- -Resemble natural metabolites which synthesize, recycle and breakdown organic compounds for use by the body.
- -Antimetabolites disrupt metabolic processes and can inhibit enzyme synthesis
- -Classified as CCS and work during the S phase (DNA sythesis & metabolism) of cycle.
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Antimetabolites
-Classifed according to the substance with which they interfere:
-Methotrexate -_________ antagonist
-5-FU- _________ antagonist
-6 mercaptopurine- _________ antagonist
-Fludara- _________ inhibitors
Antimetabolites
- -Classifed according to the substance with which they interfere:
- -Methotrexate -folic acid antagonist
- -5-FU- pyrimidine antagonist
- -6 mercaptopurine- purine antagonist
- -Fludara- adenosine deaminase inhibitors
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Drug interactions
-Numerous drugs interact with antimetabolites including _________, _________, _________, _________ inhibitors & _________ herbs.
Drug interactions
-Numerous drugs interact with antimetabolites including ASA, NSAIDS, BACTRIM, COX-2 inhibitors & OTC herbs.
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Antitumors Antibiotics
-_________-severe cardiactoxic effects - must be given with caution
-_________ function must be assessed prior to use
.-_________ causes pneumonitis-> pulmonary _________
Antitumors Antibiotics
- -Adriamycin-severe cardiactoxic effects - must be given with caution
- -Cardiac function must be assessed prior to use.
- -Bleomycin causes pneumonitis-> pulmonary fibrosis
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Mitotic Inhibitors (Plant Alkaloids)
-______- block cell division at the ______ phase (mitotic phase) of the cell cycle
-______ alkaloids- "neuro twins" ______ & ______, ______l
-Cause ______ alopecia, constipation, N&V, diarrhea, reversible & irreversible ______.
-Watch for ______ of fingers & toes "______ syndrome"
Mitotic Inhibitors (Plant Alkaloids)
- -CCS- block cell division at the M phase (mitotic phase) of the cell cycle
- -Vinca alkaloids- "neuro twins" Vinblastine & vincristine, Paciltaxel
- -Cause leukopenia, alopecia, constipation, N&V, diarrhea, reversible & irreversible neurotoxicity.
- -Watch for tingling of fingers & toes "stocking/glove syndrome"
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Liposomal Chemo
-Chemo packaged inside synthetic ______ globules called ______
-Fatty coating helps the chemo remain in the system ______ & ______ the side effects ( alopecia, N&V, cardiac toxicity) & ______ duration of therapeutic effects
-Encapsulated doxrubicin-______& ______- TCS
Liposomal Chemo
- -Chemo packaged inside synthetic fat globules called liposomes
- -Fatty coating helps the chemo remain in the system longer & decrease the side effects ( alopecia, N&V, cardiac toxicity) & increase duration of therapeutic effects
- -Encapsulated doxrubicin-Doxil & vincristie- TCS
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Hormonal Chemo
-______
-Anti______
-Anti______
-Sex ______
-______-releasing hormone analogue.
Hormonal Chemo
- -Not true chemo they are used to treat cancer
- -Corticosteroids
- -Antiestrogens
- -Antiandrogens
- -Sex hormones
- -Gonadotrophin-releasing hormone analogue.
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Hormonal Chemo
-1.Corticosteroids suppress ______ that occurs as a result of tumor growth.
-2. Sex hormones-______ & ______ - used to slow growth of hormonally dependent tumors (______ & ______) Estrogen is used to palliate ______ cancer in men & slow the growth of some ______ cancers in women.
Hormonal Chemo
- -1.Corticosteroids suppress inflammation that occurs as a result of tumor growth.
- -2. Sex hormones-estrogen & androgen - used to slow growth of hormonally dependent tumors (prostate & breast) Estrogen is used to palliate prostate cancer in men & slow the growth of some breast cancers in women.
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H
Hormonal Chemo
- -Progestins may be used in breast, endometrial & renal ca. Can cause fluid retention the clotting disorders.
- -Androgens- given to premenopausal women with advanced breast CA - will --> masculine secondary sex characteristics
- -Antiestrogens (tamoxifen) used to treat breast ca that is estrogen-receptor positive.
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T
Tamoxifen
- -Has been shown to prevent recurrence in pre & post menopausal women
- -Side effects include: flushing, irregular periods, headaches, N&V
- -In women increase the risk of developing cancer of the uterus
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A
Antiandrogens
-Casodex- used to treat men with hormone-responsive prostate cancer.
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A
Aromatase Inhibitors
- -Post menopause, the androgen is converted to estrogen
- -Aromatase inhibitors block the peripheral conversion of androgen to estrogen --> suppression post menopausal synthesis of estrogen
- -Used in the treatment of hormonally sensitive breast cancer in post menopausal women & premenopausal women who have had their ovaries removed.
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T
Targeted therapies to treat cancer
- -New approach to cancer treatment
- -Work by interfering with cancer cell growth and division in different ways and at various points in the development, growth & spread of cancer
- -Blocking signals that tell cancers cells to grow & divide uncontrollably, targeted cancer therapies can help stop the growth & division of cancer cells.
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D
Downstream Signal Transduction
- -Transmission of signals may come from outside the cell as a growth factor protein (ligand) which binds to a receptor activating it or intracellularly where kinase (transfer enzyme) activity takes place
- -These treatments are controversial & expensive up to $ 30K per year.
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T
Toposiomerase I & II inhibitors
- -Toposiomerase I inhibitors- affect S phase (Synthesis of DNA ) Hycamtin is used for metastatic colorectal cancer & refractory ovarian cancer
- -Toposiomerase II inhibitors- work on G2 phase (cell prepares for mitosis) of cell reproduction. Etoposide given for small cell lung ca and testicular ca.
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T
Tyrosine Kinase Inhibitors
- -Protein tyrosine kinases is a family of proteins that regulate cell growth, proliferation & angiogenesis
- -These proteins are involved in normal and malignant cell growth
- -These agents act on tumor & tumor vasculature
- -Tarceva is used to treat locally advanced or metastatic non-small cell lung ca after failure of one chemo regimen
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P
Proteasome Inhibitors
- -Intracellular multienzymes that degrade proteins to eliminate cells of proteins that are not needed
- -Velcade alters proteins that regulate cell growth & division
- -used for multiple myeloma, colorectal & lung ca
- -Cancer cells are more sensitive to proteasomes than normal cells
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M
Multikinase Inhibitors
- -Newest drug approved to treated advanced renal cell ca which has a very poor prognosis
- -Nexavar can cause HTN along with cracking of skin on palms & soles and stomatitis
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A
Angiogenesis Inhibitors
- -Angiogenesis is the development of new capillaries
- -Critical for tumor growth & metastic disease
- -Angiogenesis inhibitor inhibit the formation of blood vessels needed for tumor growth & mets
- -Avstin is used for metastatic ca of the colon & rectum
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