Exam III Antineoplastic Flashcards
What is cancer?
Cancer is a disease of cell proliferation where normal cells are transformed by genetic mutation into cells with dysregulated growth
Carcinogenesis occurs in what 3 main steps:?
1) transformation
2) proliferation
3) metastasis
What is transformation?
when a cell with normal growth changes into a cell with dysregualted growth (malignancy)
What is genetic damage?
- inherited
- gene mutations that alter growth and repair
- alterations in or loss of regulatory proteins
What is proliferation ?
- Growth of transformed cells into a tumor
- Increase in the number of cells
- Dividing cells progress through a cell cycle with several phases
- MOST ANTINEOPLASTIC DRUGS TARGET DIVIDING CELLS
- SMALL RAPIDLY DIVIDING CELLS RESPOND BEST TO CHEMO
- NORMAL CELLS ALSO RAPIDLY DIVIDE, are also subjected to effects of chemo.
- RESULT: DOSE LIMITING TOXICITIES
What does the critical cell cycle events include ?
The synthesis of DNA (S phase) and the division of the parent cell into 2 daughter cells (M phase= mitosis)
Metastasis:
Cancer cells acquire the ability to ____ tissues throughout the body.
Tumor cells _______ which allows them to ______ into tissues and vessels, body cavities, spread thru lymph or blood, and _______ in a _______ location.
**As they gain mutations, their response to chemotherapy may __________ (altered receptors)
Original tumor may respond well to chemo, but _________ may be _____ responsive= ____ prognosis
invade mutate invade grow new change metastatic lesions less poor
Chemotherapy - Mechanism of Action:
Most chemo agents interfere with _________
_________ selectivity against cancer cells.
**Caner cells are MOST _________ to these drugs when the cells are actively going through the cell _______.
Metabolically active cells are MORE _____ to drugs that interfere with cell ________ and _______.
Chemo is ____ to many cells, but some are able to _______.
DNA damage is sensed by molecules that _______ the cell cycle to allow time for the damage to be repaired by ________.
If damage is not repaired, the cell ______ by a biochemically-driven programmed cell death = _____________
cell proliferation relative sensitive cell susceptible growth division toxic recover arrest p53 dies apoptosis
What is p53?
- Transcription factor that regulates the cell cycle
- functions as TUMOR SUPPRESSOR
- *HELPS TP SUPRESS CANCER; ANTICANCER MECHANISMS
What are the anti-cancer mechanisms of p53?
- Active DNA repair proteins
- hold cell cycle at G1/S regulation so that DNA repair will fix damage then cell allowed to continue cell cycle
- can initiate apoptosis is damage is irreparable
- induce growth arrest
**p53 is induced after many different _________. Examples include ________, __________, _______
**IF p53 is damaged, tumor suppression is _______________
- stressors
- UV radiation
- oncogenes
- DNA damaging drugs
- reduced
Chemotherapy - Mechanism of Action:
A cancer cell that has a defective capability for DNA repair will undergo _________
**Cancer that EXPRESS p53 (leukemias, lymphomas, testicular cancer)= HIGHLY responsive to ______________.
Cancers that acquire a mutation in _______ are minimally responsive or resistant to __________
(pancreatic, lung, and liver cancers)
apoptosis
chemotherapy
p53
DNA damaging chemo drugs
Chemotherapy - Mechanism of Action:
A single malignant cell can expand _____to give rise to a ______.
Every malignant cell must be destroyed to _______cancer.
**MULTIPLE CYCELS OF CHEMO MUST BE DONE AT HIGHEST ___________DOSE with frequent tolerable interval to achieve a cure.
_____ order kinetics = a constant fraction of tumor cells is _____ with each cycle of chemo
clonally tumor cure TOLERABLE first killed
How do solid cancers respond to chemo?
- **SOLID cancer DO NOT respond well to chemo
- Slower growth/division of these cells
- Often require radiation/surgery as well
- Resistance to chemo drugs!!! (THAT WHY WE USE COMBO DRUG THERAPY)
What does Combination Chemo include?
***Drugs that act on different molecular TARGER at DIFFERENT phases of CELL CYCLE and DIFFERENT DOSES LIMITING TOXICITIES
Combination chemo reduces the emergence of drug __________.
Allows each individual drug to be given at its _______dose
Some regimes offer _______________
**Typically use _____________ dosing
resistance
highest tolerable
*SYNERGISTIC BENEFITS
What are examples of cancers that require COMBO CHEMO?
1) Hodgkin’s disease
2) Testicular
3) Breast
4) Ovarian
5) Cervical
6) Bladder
7) Lung
8) Cancer of the head and neck
What is some general information about chemo?
- current emphasis is on combo chemo
- takes into account phase of cell cycle
- potential synergistic action
- increases efficacy
- decreases cell resistance
What happens in GO of cycle ?
resting phase
What happens in G1 of cycle ?
gap phase; occurs after mitosis; genes for replication are activated
What happens in S of cycle ?
DNA synthesis
What happens in G2 of cycle ?
second gap phase “pre-mitosis”; DNA repair progresses
What happens in M of cycle ?
mitosis
How can drugs target the cell cycle?
1) Cell-cycle specific (drugs affect 1 phase)
2) Cell-cycle non-specific (drug affects ANY/all phases)
What is a low therapeutic index?
- drugs for chemotherapy are NOT SAFE
- LACK of specificity = affect malignant cells as well as rapid but normally proliferating cells
- bone marrow, skin, intestinal mucosa
With low therapeutic index, signs of toxicity appear in which areas ?
- blood dyscrasias
- ulcerations of oral mucosa and other sites in GI
- Nausea/vomiting
What is the mechanism for Alkylating Agents?
- Transfer ally groups to important cell constituents with amino-sulfhydryl, -carboxyl-, and phosphate groups
- Alkylate DNA, probably at guanine as the primary mechanism for cell death
**interfere with DNA, RNA AND PROTEINS TO PREVENT CELL METABOLISM AND DIVISION
