Exam 3: Antineoplastic agents Flashcards
(53 cards)
Define Cancer:
A disease of cell proliferation where normal cells are transformed by genetic mutation into cells with dysregulated growth.
What are the 3 steps of Carcinogenesis:
- Transformation
- Proliferation
- Metastasis
Define the transformation step of carcinogenesis:
- A cell with normal growth changes into a cell with dysregulated growth (Malignancy)
- Genetic Damage
○ Inherited
○ Mutations that alter growth and repair
○ Alterations in or loss of regulatory proteins
Define the Proliferation phase of Carcinogenesis
- Growth of transformed cells into a tumor
- Increase in the number of cells
Most antineoplastic drugs target what activity?
Target dividing cells
Which cells respond best to chemotherapy?
- Small, rapidly dividing cells respond best
- Normal cells also rapidly divided and are also subjected to effects of chemo
Define Dose-limiting toxicity
The dosage being administered is limited because of the possibility of causing toxicity
What is the challenge of chemotherapy?
To give an adequate dose to kill the cancer cells without killing too many healthy cells
Define the Metastasis phase of Carcinogenesis
- Cancer cells acquire the ability to invade tissues throughout the body
- Tumor cells mutate which allows them to invade into tissues and vessels, body cavities, etc. and grow in a new location.
What must be taken into consideration before administering chemotherapy to a patient with metastatic lesions?
- As these cells gain mutations, their response to chemotherapy may change. (altered receptors)
- The original tumor may respond well to chemotherapy, but metastatic lesions may be less response = poor prognosis
Most chemotherapy agents interfere with what carcinogenesis phase?
Cell proliferation
When are cancer cells most sensitive to chemotherapy drugs?
- When the cells are actively going through the cell cycle
- Metabolically active cells are more susceptible to drugs that interfere with cell growth and division
What is the tumor suppressor gene that senses DNA damage and arrests the cell cycle?
- p53
This allows time for the damage to be repaired
If a cell fails to repair damage due to chemotherapy, what occurs?
- The cell dies by a biochemically-driven programmed cell death
- *apoptosis
What is the action of p53?
- Helps to suppress cancer; anti-cancer mechanisms.
- Activate DNA repair proteins
- Hold cell cycle at G1/S regulation point so that DNA repair proteins will fix damage, then cell allowed to continue cell cycle.
- Can initiate apoptosis if damage is irreparable
- Induce growth arrest.
What things might induce p53?
- UV radiation
- Oncogenes
- DNA damaging drugs
What occurs if p53 gene is damaged?
Tumor suppression is severely reduced.
Which type of cells are “highly responsive to chemotherapy”?
- Cancer cells that express p53
* includes leukemias, lymphomas, testicular cancer
Which cells are minimally responsive or resistant to DNA-damaging chemotherapy drugs?
- Cancer cells that acquire a mutation in p53
* include pancreatic, lung and liver cancers
T or F, Every malignant cell MUST be destroyed to “cure” the cancer
True, a single malignant cell can expand clonally to give rise to a tumor.
When administering chemotherapy, is there a specific dosage or cycle number that all therapies follow?
Multiple cycles of chemotherapy must be given at the HIGHEST tolerable dose with the most frequent tolerable interval to achieve a cure
Chemotherapy is under what order of kinetics?
- First-order kinetics
A constant fraction of tumor cells is killed with each cycle of chemotherapy
Which type of tumors do not respond well to chemotherapy?
- Solid tumors
Slower growth/division of these cells
Solid tumors often require what type of treatment?
Often require radiation and/or surgery as well as chemotherapy.
- Resistance to chemotherapy drugs often develops!
- Justification for using combination drug therapy
