Chemotherapy Flashcards Preview

Foundations of Disease and Therapy > Chemotherapy > Flashcards

Flashcards in Chemotherapy Deck (41):
1

Cell-Cycle Specific Drug Classes 

  1. Antimetabolites
  2. Topoisomerase Inhibitors
  3. Microtubule Inhibitors

2

Methotrexate

Antimetabolite that inhibits dihydrofolate reductase 

3

Pazopanib, Levantinib, Cabozantinib

Small molecule inhibitors of the VEGF Receptor 

4

Microtubule Inhibitors 

Block microtubule polymerization and inhibit mitosis 

Can cause neurotoxicity and peripheral neuropathy because microtubules are important for transport of cargo along neurons

Induce resistance via MDR1

 

5

Imatinib, Dasatinib, Ponatinib

Small molecule inhibitors of BCR-Abl tyrosine kinase that causes CML

Effective single-agent therapy that causes long-lasting remission 

Resistance is driven by mutations in BCR-Abl that prevent binding of the drug, but the drug can be modified to combat these mutations 

6

Strategies to maximize efficacy of treatment and minimize side effects

  1. Combination Therapy
  2. Rationaly Designed Therapies
  3. Prophylaxis
  4. Intermittent therapy
  5. Optimization of dosing and route
  6. Support of bone marrow function 

7

Cell Cycle Nonspecific Drug Classes

  1. DNA Intercalating/Damaging Agents
  2. Alkylating Agents
  3. Protein Synthesis Inhibitors 

8

Inhibit mutant B-Raf kinase

Vemurafenib, Dabrafenib

9

MDR1

Multi-Drug Resistance 1 gene

Recognizes toxic compounds and pumps them out of the cell 

Expression of MDR1 increases dramatically over course of treatment

Allows cell to develop resistance to chemotherapeutics such as Microtubule Inhibitors and Topoisomerase Inhibitors 

MDR1 is non-selective, so resistance to one drug gives resistance to many other drugs 

10

Trastuzumab

(What is it, and what are the side effects?)

Monoclonal antibody against HER2 receptor 

Can cause heart toxicity when used with Doxorubicin 

11

Anti-Angiogenesis Drugs

(Mechanism)

Target VEGF

Theoretically stop cancer by preventing blood supply to cancer 

12

Purpose of combination therapy

Using multiple mechanisms makes cells less likely to develop resistance

Therapy is more effective because you are targeting multiple pathways 

Fewer side effects because you can use less of each drug 

13

Topoisomerase Inhibitors

Topoisomerase is required for DNA replication and mitosis

These drugs induce resistance via upregulation of MDR1

14

Panitumumab 

Monoclonal antibody against Epidermal Growth Factor Receptor

Treats EGFr-expressing metastatic colorectal carcinoma 

High dermatologic toxicity 

15

Examples of Alkylating Agents

  1. Nitrogen Mustards
  2. Nitrosoureas
  3. Hydrazines
  4. Platinum Compounds 

16

Drug that can cause cardiomyopathy due to free radical generation as well as red urine 

Doxorubicin 

17

Tamoxifen

Hormonal therapy that acts as an antagonist to estrogen receptor

Used to prevent estrogen-receptor positive breast cancers

Less effective in pre-menopausal women cause they have more estrogen  

18

Estrogen Receptor Antagonist

Tamoxifen 

19

Tumor lysis syndrome 

Occurs when a chemotherapeutic drug is so effective that proteins from lysed tumor cells can cause kidney failure 

20

If RAS is mutated, would targeting a growth factor receptor be effective?

NO; RAS is downstream of growth factor receptors and is operating independently if mutated 

21

Vemurafenib, Dabrafenib

small molecule inhibitors of mutant B-Raf kinase

This mutation is present in most melanomas 

Resistance may develop months later with elevated ERK signaling 

22

Longest parts of cell cycle? Shortest?

G1 and S phase take up around 40% of the cell cycle each 

M phase takes up only 2% of the cell cycle 

23

Rationally Designed Therapy

Drugs that target causitive molecular abnormality of fundamental, universal cellular processes

Require precise knowledge of cause of disease 

Include:

  1. Small molecule inhibitors
  2. Antibodies 

24

Antibiotics

Intercalate into DNA, cause single strand DNA breaks, and prevent transcription

Toxicity associated with longterm use 

Minimally myelosupressive and immunosuppressive 

25

Alkylating Agents

Highly reactive compounds that crosslink DNA and proteins

Prevent DNA replication and transcription of RNA

High toxicity to bone marrow and intestinal mucosa

All are mutagenic/carcinogenic and can induce secondary leukemia 

Cells mutant for p53 have intrinsic resistance 

26

5-fluorouracil 

Antimetabolite that inhibits synthesis of thyidine from uracil

Potent radiosensitizer ; useful for locally advanced and accessible tumors

27

Venetoclax

Used to treat CLL where there's an overexpression of Bcl-2

It acts as a Bcl-2 antagonist in order to allow apoptosis 

May lead to Tumor Lysis Syndrome 

28

Antimetabolites

Analogs of molecules required for DNA Synthesis (amino acids and vitamins)

S Phase Specific

Most effective for rapidly proliferating tumors - all cause myelosuppression (decreased bone marrow)

29

Aromatase Inhibitors

Exemestane and Anastrozole 

Block Aromatase, which is responsible for synthesis of estrogen 

30

Cells with a p53 mutation have intrinsic resistance to what class of drugs?

Alkylating Agents 

31

Rituximab

Monoclonal antibody that binds CD 20

Found on 90% of non-Hodgkin's lymphomas 

Can cause Tumor Lysis Syndrome 

32

GnRH Analogs

Leuprolide, Goserelin

Block sex hormone synthesis in testes and ovaries

33

Bevacizumab

Humanized antibody to VEGF that prevents it from binding to receptors 

34

PD-1

Receptor on T cell that reduces cytotoxic activity when stimulated 

35

Support Therapy

Drugs designed to support bone marrow function, etc

These drugs enable patients to tolerate chemotherapy, but do not play any role in killing cancer 

36

Nivolumab, Pembrolizumab

Binds PD-1 on T cell and prevent inhibitory signal, thus allowing T Cells to kill cancer cells via production of IL-2 and Interferon 

37

Trametenib

Inhibit MEK1 and MEK2 (downstream substrates of B-Raf)

Used in combination with B-Raf inhibitors 

38

Inhibits MEK1 and MEK2

Trametenib

39

Progestins

Megestrol

Inhibit pituitary release of gonadotropins and can stimulate apetite in patients with cachexia 

40

Antiandrogens

Used to treat prostate cancer

Steroidal Antiandrogens - inhibit androgen binding to receptor (cyproterone)

Non-steroidal Antiandrogens - inhibit nuclear translocation of receptor (bicalutamide)

Basically they inhibit Androgen Receptor-dependent gene transcription 

41

Doxorubicin and Daunorubicin

Members of Antibiotic class (DNA Damaging drugs)

Doxorubicin causes unusual cardiomyopathy due to free radical generation 

Also causes Red Urine

Induces upregulation of MDR1 and has resistance