Anineoplastic and Anticancer Agents - Farrell Flashcards Preview

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Flashcards in Anineoplastic and Anticancer Agents - Farrell Deck (80)
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1

What is cancer?

Loss in normal mechanisms that govern cell survival, proliferation, and differentiation
They keep growing, even where there is no space, when most cells stop

2

Causes of cancer (2)

1. Oncogenes
2. Tumor suppressor genes

3

Oncogenes

Normally tightly regulated growth and differentiation of cells
ie. Bcl-2: unregulated or deregulated in cancer

4

Tumor suppressor genes

Normally suppress overgrowth of cells
ie. p53: down regulated or absent in many cancers

5

Causes of cancer

Genetics
Environmental

6

Most common forms of cancer

Lung, prostate, breast, colorectal

7

Cancer pathophysiology (3)

1. Initiation
2. Promotion
3. Progression

8

Initiation

Chemical or physical carcinogen causes mutation
Not identified as foreign by immune system

9

Promotion

Growth factors and promoters of cell proliferation

10

Progression

Transformation to malignant from benign
Further mutation and variation with tumor

11

Stages of cancer

Stage 0-IV
0: early, not detectable
I-III: higher number reflects size and spread
IV: invasion of other tissues and metastasis

12

How is cancer treated? (3)

1. Surgical removal of tutor
2. Radiation
3. Chemotherapy

13

Targets of chemotherapy (3)

1. Target cell cycle
2. Target proliferation pathways
3. Target cancer specific molecules

14

Traditional antineoplastic agents

Target cell cycle
Kill rapidly dividing cells
1. Alkylating and platinum agents
2. Antimetabolites
3. Topoisomerase inhibitors and antibiotics
4. Vinca alkaloids
5. Taxanes

15

Newer anticancer drugs

Target proliferation pathways

16

Target anticancer agents

Target cancer specific molecules
1. Cellular markers
2. Growth and proliferation
3. Angiogenesis
4. Hormone sensitive growth

17

Principles of chemotherapy (3)

1. Chosen agent must be tolerable
2. Dose and regiment must be chosen to maximize effectiveness
3. Use combinations to increase efficacy

18

MTD

Maximum tolerated dose

19

Cyclic therapy

Multiple cycles of therapy to combat multiple growth cycles of tumor

20

Alkylating agents

Crosslink DNA causing damage and death
Groups of agents based on their structures
1. Bis(chloroethyl)amine group
2. Platinum containing agents

21

Bis(chloroethyl)amine

Alkylating agent
ie. Cyclophosphamide

22

Cyclophosphamide

Needs to be activated in liver
Metabolites cross-link DNA by binding
Can bind other molecules with similar functional groups (SH, OH, NH) like lipids and proteins

23

Platinum containing agents

Similar to alkylating agents but do not necessarily contain alkyl groups
Cause inter and intra DNA strand cross-links in cells

24

Antimetabolites

Similar in structure to endogenous compounds like Folic acid and nucleotide bases
Interfere with nucleotide synthesis
Prevent DNA synthesis
ie. Mercaptopurine, fluorocuracil, folic acid antagonists

25

Mercaptopurine

Structurally similar to adenine
Interacts with enzymes involved in purine nucleotide synthesis
Incorporated into RNA and DNA but unable to correctly basepair
Interferes with DNA replication and RNA translation

26

Fluorouracil

5-FU
Similar in structure to uracil and thymine
Binds to thymidylate synthase
Prevents further synthesis of thymide nucleotides

27

Folic acid antagonists

Folate, folic acid, vit B9
Essential cofactor in DNA and protein synthesis
Includes methotrexate

28

Methotrexate

Structurally similar to folic acid
Prevents nucleotide synthesis by eliminating cofactor

29

Topoimerase I inhibitors

ie. Topotecan
Bind to topoimerase I
Produces complex that prevents further DNA replication and transcription
Halting replication process signals cell death

30

Topotecan

Topoimerase I inhibitor, fixed enzyme to DNA
Replication cannot procede