Term
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Definition
- surgery
- radiation
- chemotherapy
- molecularly targeted products
- vaccination
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Term
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Definition
- palliation
- partial remission
- complete remission (no visible symptoms)
- cure (5 yr survival)
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Term
| General priniciple of the action of effective antitumor chemotherapy. What makes a tumur resistant? |
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Definition
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Term
| % of patients requiring chemotx |
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Definition
| 60% (cant be cured with surgery or radiation) |
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Term
| Define adjuvant chemotherapy and neoadjuvant chemothearpy |
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Definition
- adjuvant chemotherapy refers to drug tx after surgery/radiation
- neoadjuvant chemotherapy is before surgery/ radiation
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Term
| define a secondary cancers and what agents are most associated with it |
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Definition
- cancer that develops after survival of previous (usually childhood) cancer
- due to radiotherapy tx and use of anticancer agents like:
- alkylating compounds
- Pt compounds
- topoisomerase inhibitors
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Term
| Why is it difficult to achieve selective toxicity against highly differentiated tumor cells? Why it so difficult to treat poorly differentiated tumors? |
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Definition
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Term
| General prinicple of tissues that are affected adversely by chemotx drugs |
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Definition
- drugs will produce toxicity to normal tissues that grow rapidly
- bone marrow
- GI
- hair follicles
- reproductive cells
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Term
| Nature of therapeutic index of cancer chemotherapy drugs |
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Definition
| Most have low TI's (lack of selectivity) |
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Term
| tx with low hematological toxicity |
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Definition
- vincristine
- bleomycin
- cis-platin
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Term
| What factors present opportunities for antitumor selectivity? |
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Definition
- radio-iodine and thyroid
- drugs acting on specific organs
- mitotane (adrenal cortex)
- streptozocin (beta pancreatic cells)
- biochemical differences between tumor and normal cells: asparaginase)
- tissue dependent on hormones (estrogens)
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Term
| equation for growth fraction |
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Definition
| GF = (cells in mitotic cycle)/(total number of cells) |
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Term
| Tumor in the cell cycle: what is the advantage of the tumor going into G0 phase |
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Definition
- they can rest and:
- hide from synthesis inhibiting antitumor drugs
- die
- or be recruitied again into mitotic cycle
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Term
| Growth fraction and its relation to chemotx sensitivity |
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Definition
- higher GF means more sensitive to chemotherapies which inhibit biosynthesis (remember, drugs are selective for high GF)
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Term
| There is a difference between actively growing tumor cells and select tumor stem cells that cause reinitiation of tumor. Explain this difference and its importance. |
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Definition
- the stem cells are rare and difficult to isolate
- the active growing tumor cells are more sensitive to the anti tumor drugs (large GF)
- so if you shrink the tumor, that doesnt mean you have completely erradicated and cured the tumor (unaffected tumor stem cells)
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Term
| Effect of anti tumor drug on cell population once given |
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Definition
- cell population will drop by a predictable and fixed precentage, and thereafter resumes its logarithmic rate
- this produces a delay in death and an increase in survival time of the animals (aka remission)
- higher dose cause further delay, assuming no toxicity
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Term
| Typical clinical situation of dx of tumor |
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Definition
- tumor dx occurs relatively late
- repeated drug tx can produce small decreases in tumor burden, but regrowth will eventually kill the patient
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Term
| Effect of surgery and adjuvant therapy |
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Definition
| surgery produces a "debulking action" and the chemo could be successful with tolerable toxicity |
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Term
| In order for a tumor to be sensitive to a drug, it must have two qualities. what are they |
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Definition
| drug uptake and drug retention |
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Term
| Emergence of multidrug resistance: type of drugs that tend to cause this phenomenon and cell surface protein seen in these types of tumors |
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Definition
- large number of lipid soluble but chemically unrelated drugs
- usually contain P-170 (specific glycoprotein)
- uses ATP to pump antitumor drugs out of cell
- also could contain MRP (an ABC transporter)
- these proteins lead to repair of drug produced damage, but more likely, enhance drug efflux
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Term
| Potential of blocking P-170 to prevent MDR tumors |
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Definition
| potentially valuable, but toxicity would prevent its use |
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Term
| Advantage of using alkylating agents and certain antibiotics in tx of cancer |
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Definition
- they are not cell cycle specific
- so they are effective on resting/G0 phase as well as during the mitotic cycle
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Term
| Explain the difference between revovery time of normal tissue and tumor cells from tx with anti-tumor drugs. clinical application? |
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Definition
- normal tissue recovers much faster from tx than the tumor cells
- clinical application
- we can carefully time the second and subsequent doses when normal tissue function is restored and tissue function is not
- we select times of drug readministration when recovery of normal tissue is complete but the tumor is still not vulnerable
- during recovery of DNA synthesis, the tumor and normal tissue are very vulnerable to subsequent tx
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Term
| Describe toxicity as it relates to dose scheduling |
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Definition
- minimal toxicity results to normal tissue along with maximal increase in mean survival time if you give a second dosage at day 7-8
- before tumor cells recovery is complete
- maximal toxicity would result if give a second dose after 2-3 days (at this point, normal tissue has not recovered)
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Term
| major problems limiting success of chemotx |
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Definition
- susceptibility differences between tumor stem cells and other tumor cells (TSC are usually less susceptible)
- insufficient selective toxicity of drugs against tumor cells (fail to locate and exploit differences between malignant and normal tissue)
- lack of predictive in vitro test models for drug susceptibility
- imperfect animal models of solid human tumors
- incomplete understanding of antitumor drug metabolism and PK
- poor host defense against residual tumor cells
- tumor cell sanctuaries not adequately penetrated by antitumor drugs
- initial large tumor cell populations due to late cancer dx
- secondary cancers due to carcinogenic action of certain anti-tumor drugs
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