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Flashcards in Anti-tumor agents Deck (45)
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1
Q

What is Primary Induction Chemotherapy?

A

no surgery or radiation is used. The Goal is just to palliate tumor-related symptoms and extend life a little longer.

2
Q

What is neoadjuvant chemotherapy and when would you use it?

A

This is used for localized cancer before surgery/radiation where surgery/radiation is not completely effective. The goal is to make surgery/radiation more effective

3
Q

What are some benefits of neoadjuvant chemo?

A
  • can spare vital organs

- may kill (micro)metastatic disease-easy to measure the response because can remove the tumor mass and characterize.

4
Q

What is adjuvant chemo and when do you use it?

A

Used after surgery/radiation. The goal is to kill micrometastases and increase the effectiveness of surgery/radiation by increasing relapse-free survival

5
Q

It is easy to measure the response of adjuvant chemo, T or F?

A

F. It is hard because the tumor has been removed. Instead survival is measured.

6
Q

What diseases would you treat with Primary induction chemo?

A

Hodgkins and non-hodgkins lymphoma, germ cell cancers, ALL, Wilms tumor, embryonal rhabdosarcoma.

7
Q

What diseases would you treat with Neoadjuvant chemo?

A

anal, breast, bladder, esophageal, head and neck, gastic rectal, osteogenic, soft tissue sarcomas

8
Q

What diseases would you treat with adjuvant chemo?

A

breast, colorectal, gastric, non-small cell lung cancer, melanoma

9
Q

How do conventional cytotoxics work?

A

drug kills tumor cells by forcing the cell into apoptosis via cellular damage. This will also affect regular cells.

10
Q

Patients given conventional cytotoxics are treated with the ______ dose while those given targeted therapy are treated with the ______ dose.

A
  • maximally tolerated dose (MTD)

- person’s optimal biologic dose for inhibition (OBD)

11
Q

Targeted therapy drugs work by causing ______ in cells while conventional therapy drugs work by causing ______ in cells.

A
  • death or growth arrest (in cells containing the defect)

- apoptosis (in tumor cells but will also affect regular cells)

12
Q

In conventional cytotoxics drugs are chosen based on _____ while in targeted therapies drugs are chosen based on_____.

A
  • tumor site (not specific defect)

- the particular defects that cause a patients cancer.

13
Q

Do cytotoxic agents target specific pathways?

A

yes, they just target them in all cells unlike targeted therapies which attempt to target specific pathways in damaged cells only.

14
Q

What is the basis for combining drugs in treating cancer?

A

clinically tolerable doses of drugs usually aren’t strong enough to kill cancer. If individual drugs are at least partly effective in the patient then they should be combined.

15
Q

Why is it dangerous to reduce the dosage or completely remove a drug from the regimen?

A

can allow a resistant cell line to proliferate.

16
Q

Why is inconsistency bad in giving cancer drugs?

A

patients can build up a resistance if given too much time in treatment free interval.

17
Q

For targeted pathways you should combine drugs that target ___ steps in the same pathways

A

different. Or combine drugs that target separate (but involved) apoptotic mechanisms

18
Q

Explain how cancer cells have a strong selective pressure to adapt.

A

They are trying to avoid drugs. can have mutations that affect the cellular target or which enhance the repair mechanism to prevent apoptosis. Can create tumor stem cells which resist the drug repopulate tumor with resistant cells.

19
Q

How do cancer cells resist destruction?

A
  • they have mutations that affect the cellular target of the drug, or can enhance its excretion or decrease uptake
  • mutations prevent apoptosis.-mutations enhance repair mechanisms-Can get tumor stem cells which are resistant and re-populate the tumor with resistant cells
20
Q

How do alkylating agents work?

A

form covalent chemical adducts and interstrand crosslinks in DNA. This prevents DNA replication and causes apoptosis

21
Q

What is an example of an alkylating agent and what is it used for?

A

Cyclophosphamide used in breast cancer and lymphomas

22
Q

What inactivates alkylating agents?

A

GSH (Glutathione)

23
Q

How are alkyl groups and inter-strand crosslinks removed from DNA?

A

DNA repairinterstrand crosslinks are removed by DNA repair via NER

24
Q

Why must alkylating agents be carefully dosed?

A

causes hematopoietic toxicity, kills hematopoietic stem cellscan cause other toxicities and lead to carcinogenesis (leukemia and solid tumors)

25
Q

How do Platinum-based compounds work?

A

crosslink DNA via interstrand CpG crosslinks- makes replication impossible and causes apoptosis

26
Q

what are examples of platinum based compounds?

A

anything that ends in-platin (cisplatin etc..)

27
Q

How does the body resist platinum-based compounds?

A
  • reduced drug uptake/increased efflux
  • inactivation by GSH
  • DNA repair and increased tolerance for damage
28
Q

What are risks for toxicity from platinum based compounds?

A

nephrotoxicity, ototoxicity, platelet toxicity, sensory neuropathy

29
Q

How do anti-metabolites work (methotrexate)

A

reversible, competitive inhibitor of dihydrofolate reductase (DFHR) which is required for the synthesis of purine nucleotides.

30
Q

What is methotrexate used for?

A

hematological malignancies.

31
Q

How does the body resist antimetabolites?

A

increased expression of DHFR. DHFR with decreased MTX (methotrexate) binding affinity. decreased capacity to make polyglutamated MTX

32
Q

How do antimetabolites work (5 FU)?

A

pyrimidine analog. dTTP depletion inhibits DNA snthesis

33
Q

Common toxicity caused by antimetabolites (5FU and MTX)

A

myelosuppression

34
Q

Resistance to antimetabolites (5 FU)

A

alterations in target enzyme TS, reduce affinity for FdUMP (FdUMP is what inhibits DNA synthesis)

35
Q

Topoisomerase interacting agents mechanism of action.

A

Drugs inhibit Topoisomerase ability to unwind the DNA.

36
Q

Toxicity from topoisomerase interacting agents?

A

Anthracyclins cause cardiotoxicity. Myelosuppression

37
Q

What are examples of Antimicrotubule agents?

A

Vinblastine, vincristine, taxanes

38
Q

How do antimicrotubule agents work?

A

Vinblastine/vincristine: binds microtubule ends causing depolymerizationTaxanes: stabilize MT; prevents depolymerization but blocks mitosis

39
Q

Resistance to antimicrotubule agents?

A

tubulin mutations

40
Q

toxicity from antimicrotubule agents?

A

vincristine: neurotoxicityvinblastine, taxanes: myelosuppression

41
Q

How do hormonal agents work?

A

work on steroid (nuclear) receptors. Tamoxifen blocks steroid binding to estrogen. Anti-androgens bind androgen receptors preventing their function

42
Q

Examples of hormonal agents?

A

tamoxifen, anti-androgens

43
Q

How do antibodies work (with respect to cancer)?

A

inhibit function at target (Avastin blocks VEGF from stimulating factor)cell mediated toxicity by antibody binding to tumor antigens. immunoconjugates deliver toxins to tumor cells.

44
Q

How do kinase inhibitors work?

A

prevent the binding ability of tyrosine kinase receptors or prevent phosphorylation activity by acting as an ATP analog

45
Q

What are examples of kinase inhibitors?

A

imatinib, dasatinib, Gleevec