DDT 10 - Chemotherapy drugs (mode of action) II

Question 1

alternative to chlormethine

Answer 1

chloroambucil
melphalan
estramustine
uracil mustard

Question 2

describe chloroambucil and name their properties

Answer 2

Aromatic ring is electron withdrawing
Lowers nucleophilic strength of nitrogen
Less reactive alkylating agent
Less side reactions and less toxic

Question 3

describe properties of mephalan

Answer 3

Aromatic ring is present
Less reactive alkylating agent
Mimics amino acid phenylalanine
Transported into cells by transport proteins

Question 4

urethran

Answer 4

more hydrophic can pass through membrane through passive diffusion
steroid is hydrophobic
urethrane group is draws electrons

Question 5

uracil ring

Answer 5

Uracil ring is electron withdrawing
Less reactive alkylating agent
Mimics a nucleic acid base
Concentrated in fast growing cells

Question 6

effect of DNA Alkylation

Answer 6

Alkylated guanine prefers enol tautomer
Alkylated guanine is hydrogen bond
donor / acceptor / donor

Question 7

pro drug alkylating anti-cancer

Answer 7

pro drug - have to be activated
e.g Cyclophosphamide oxidised by cytochrome P450 enzyme
nitrosoureas - desompose in the body to form activating agent

Question 8

how does busulfan a DNA alkylating agent - cause interstrand crosslinking

Answer 8

SN2 reaction

Question 9

describe the mechanism of the interstrand cross linking of busulfan

Answer 9

electron from nitrogen in guanine base pair moves to C in busulfan
with the help of Mesylate (MeSO3 - a good leaving group) electron from Nitrogen in the Cytosine in the other end of the DNA strand to C then electron from C busulfan moves to O in busulfan
mesylate helps form the cross link

Question 10

mitomycin C

Answer 10

Prodrug activated in the body to form an alkylating agent
One of the most toxic anticancer drugs in clinical use
Mode of action is via DNA alkylation

Question 11

where does CC1065 bind to and is it more or less active than cisplatin

Answer 11

Naturally occurring agent
Binds to minor groove of DNA
Alkylates adenine bases
1000 times more active than cisplatin in vitro

Question 12

oestrogen antagonist

Answer 12

Agents that antagonise the action of oestrogens are of interest
for the treatment of oestrogen dependent breast cancer

Question 13

example of oestrogen antagonist

Answer 13

tamoxifen -used to treat estrogen hormone dependant breast cancer

Question 14

17-Beta Estradiol

Answer 14

17β-Estradiol is a steroid hormone

that promotes the growth of certain tissues

Question 15

how does tamoxifen treat hormone dependent breast cancer

Answer 15

binds to the estrogen receptor binding site without fully activating the receptor and prevents 17β-estradiol from binding

Question 16

antimetabolites

Answer 16

are compounds that prevent the biosynthesis of normal cell metabolites

Question 17

example of antimetabolites

Answer 17

5-Fluorouracil (5-FU)

Question 18

principle of anti metabolites

Answer 18

Structurally designed compound based on the experimental observation that some tumour cells preferentially use uracil for the synthesis of the DNA base thymidine using a biosynthetic pathway not used by normal cells

Question 19

monoclonal antibodies

Answer 19

produced for several tumour
associated antigens and can act to activate the body’s immune
response to direct killer cells against the tumour.

Question 20

why are able to use monoclonal antibodies

Answer 20

Cancer cells have altered plasma membranes that contain
distinctive antigens which are over expressed
when compared to normal cells.

Question 21

what type of cancer does monoclonal antibodies treat/

Answer 21

breast cancers
colorectal cancers
lymphomas

Question 22

example of monoclonal antibody

Answer 22

herceptin

rituximab

Question 23

what does herceptin target and why

Answer 23

which targets the HER-2 growth factor receptor which is over expresses on 25% of breast cancers.

Question 24

what type of cancer does herceptin treat?

Answer 24

treatment of HER-2 positive metastatic breast cancer in combination with the mitotic inhibitor paclitaxel (targets tubulin)

Question 25

rituximab is against what protein?

Answer 25

CD20 found on the surface of immune system B cells

Question 26

rituximab is used to treat what kind of cancers

Answer 26

used to treat diseases which are characterized by excessive numbers of B cells or dysfunctional B cells
This includes many lymphomas and leukaemias

Question 27

Combination therapy - R-CHOP

Answer 27

one of the more widely used combination chemotherapy regimens.

Question 28

R-CHOP used for what type of cancer?

Answer 28

approved R-CHOP as a first line treatment
for non-Hodgkin’s lymphoma (NHL), B-cell NHL subtypes, including follicular lymphoma,
mantle cell lymphoma, Burkitt’s lymphoma

Question 29

what does a course of R-CHOP look like?

Answer 29

R-CHOP involves 6 to 8 treatments separated by 21 days with

Question 30

examples of alkylating anti-cancer drugs of chlormethine analogues

Answer 30

chlorambucil
melphalan
urethane
uracil mustard

Question 31

list pro-drug alkylating anti-cancer

Answer 31

cyclophosphamide
nitrosoureas: lomustine and carmustine
busulfan
mitomycin C
CC1065
Tamoxifen

Question 32

name 2 Monoclonal antibodies

Answer 32

Herceptin used w/ Paclitaxel

Rituximab