Chemo I: Overview Flashcards
What is the aim of chemotherapy (4)
Eradicate a cancer (over or covert)
Prevent the death of the patient
Prolong the life of the pt / palliative care (DEC sx /make life better)
Cancer is an accumulation of ________ (2) and is a _______ process
What is the phenotypic change of cancer?
Cancer is an accumulation of GENETIC ALTERATIONS and is a multi-step process
Transformation - change to the malignant phenotype
What are the phases of the cell cycle?
(describe the basic fxn of each)
How do tumor cells differ?
Phases of the cell cycle: G0, G1, S, G2, M
G0 = non-dividing
G1= Synthesis of compenents needed for DNA synthesis
S = DNA synthesis
G2 = synthesis of components needed for mitosis
M = mitosis
Tumor cells have survival advantage over the surroudning cells;
CONTINUED CELL DIVISION occurs until the cancer becomes clinically detectable
Describe the growth curve of cancer cells:
Approx how many cell divisions turn a subclinical tumor to a clinically detectable tumor?
What two important factors allow for further growth of the tumor?
what is the underlying
A cell gains the ability to continually divide/unchecked division and goes a period of latent growth prior to clinical detection =subclinical/latent phase
It is YEARS (believed ~30 doublings = 1 billion cells) before a cancer becomes of “clinical growth” and person will have some symptoms
Because the DNA is inheritably unstable —> further mutations will allow for two important factors:
- Clones that gain the ability to metastasize
- Clones that gain the ability to be chemoresistant (biggest reason why chemotherapy will fail the patient = drug resistance)
* these gains evolve by chance, random, spontaneous events - most likely before medicaiton has even begun*
What is tumor heterogenity?
three examples
Tumor cell heterogeneity = although cancers look similar under the microscope, the cells can be categorized w/respect to a # of different characteristics -
Examples: growth fraction (dividing cells / total cell number) metastatic potential and process
Resistance / sensitivit to chemotherapy
- some of the cells may have the capability to metastasize, some may be sensitive to chemotherapy others resistance*
- Also, neoplastic cells may be in different parts of the cell cycle (some could be actively dividing while others aren’t)*
What are the steps to the metastatic process? (4)
When does this process usually occur?
From primary site of cancer –> distant organs via hematogenous process or other processes = metastatic
- Clonal evolution - produce cells that gain this ability
- Intravasation
- Extravation
- Growth in the distant metastatic site
* this usually cocurs during the latent or subclinical phase of tumor growth*
(example if a person has breast cancer that has metastasize to the liver, the person has metastatic breast CA to the liver but does not have both breast CA and liver CA)
What is the TNM classification of cancer staging?
What are the three basic stages?
What are the predictive prognosis based on based on the TNM?
TNM classifies the stage of cancer / extent of disease at the time of diagnosis
Determines prognosis and treatment
Based on:
1- cancer localized to the organ of origin
2- cancer localized to the organ of origin with spread to the regional draining lymph nodes
3-Disseminated disease
The stage assess the RISK THAT THE CANCER MAY HAVE UNDERGONE THE METASTATIC PROCESS during the subclinical or latent period of growth
Prognosis: Local > local-regional > metastatic
Metastatic rate: local-regional > local
What accounts for the majority of failure of chemotherapy?
How can we determine the ability of chemotherapy to cure a tumor?
Malignant cell resistance to chemotherapy accounts for the failure of chemotherapy to completely eradicate a malignant process. Resistance to chemotherapy could occur at any time during the natural history of a cancer
The ability of chemotherapy to cure is inverseley proportional to the tumor burden (Skipper Hypothesis)
the more # of tumor cells = the least likely to cure
What are some types of cancer treatments (4):
Surgery to remove all cancerous cells
Radiation therapy
Chemotherapy - drugs given to patients w/malignant process
Other localized therapies - embolization (cut off blood supply), radiofrequency ablation, regional organ perfusion
What is chemotherapy designed to do?
What are the different possible outcomes?
How can you asses the response to chemotherapy (4):
Chemotherapy are drugs developed/designed/selected to KILL mammalian cells; reduce the total body cancer burden by killing cancer cells
Complete eradication? pt will be cured (all cells sensitive to chemo)
Incomplete? life of the patient may be prolonged (some or all cells resistant to chemo); unless you can find OTHER chemo drugs that pt could be sensitive to, patient won’t be cured
Assessment of response to chemotherapy:
cat scan to obtain baseline, give TX + new cat scan….
Complete remission
partial remission (>50% redution + no new lesions)
stable dz - no new growth
progression of disease - bigger or new sites
What is the effect of chemotherapy on non-neoplastic / healthy cells?
The drug is taken up by both cancer and normal cells. The effect of the drug on the normal cells is responsible for the TOXICITY / side effects of the drug
The MOA of the drug is responsible for the lethal effect on the neoplastic cell = cytotoxicity (may or may not be responsible for side effects of the drug)
What are examples of chemocurable cancers?
disseminated testicular CA, some lymphomas, some leukemia’s and hodgkin’s diseaes
Chemocurable cancers never develope resistance to chemotherapy
What are the two categories of chemotherapies?
Cell cycle specific
Cell cycle non-specific
What are the phases of drug development? (4)
- Preclinical testing - drug co are responsible; lots of pre-work
* background info, compared to what’s currently available; needs to meet a need* - Phase I clinical trials - determine dose and dose limiting toxicity
- Phase II clinical trials - determine activity
- Phase III clinical trials - determine efficacy
What does scheduling refer to? (4)
What effect does scheduling have on cytotoxicity and toxicity?
Effective cancer treatment require the repeated cyclical administration of drug/s
Scheduling refers to:
Dose (mg/M^2 of body surface area), route of administration (most IV), frequency of administration and cycle length (21-28 day intervals to allow for pt to recover from side effects of drug tx)
There is both: schedule dependent cytotoxicty (the efficacy of cancer cell kill depends critically on the schedule of drug administration) and scheduled dependent toxicity (the types of side effects the patient experiences dependent upon the schedule)
(frequency of neoplastic cell death / side effects)
