Anti-cancer Agents 1

Question 1

What are the three main approaches to eliminating cancer?

Answer 1

1) surgical excision (local) 2) radiotherapy (local/regional) 3) chemotherapy (systemic/targeted)

Question 2

what is adjuvant therapy? What is neoadjuvant therapy?

Answer 2

adjuvant therapy= systemic chemotherapy used in patients with primary tumour removed but who are at high risk of metastatic disease neoadjuvant therapy = treatment given prior to local therapy to ‘shrink’ the tumour before surgery

Question 3

How does chemotherapy generally work?

Answer 3

It exploits the existing differences between the tumour and host cell - ideal chemotherapy drugs are selective for the malignant cells and leave the host cells unharmed

Question 4

What are the 3 stages of tumour growth?

Answer 4

A= dividing B= resting, but capable of division (most dangerous b/c it’s not targeted by chemo then) C= no longer capable of cell division

Question 5

What are the four classes of cytotoxic drugs?

Answer 5

1) antimetabolites 2) alkylating agents 3) cytotoxic antibiotics 4) plant alkaloids/microtubule inhibitors

Question 6

How do antimetabolites work?

Answer 6

they act by competition, block, or subvert metabolic pathway in the biosynthesis of DNA/RNA so the tumour cell can not continue to divide

Question 7

What class of drug is a folate antagonist? How does it work?

Answer 7

it is an antimetabolite. Folates are used normally in the body to synthesise purine nucleotides like guanine and adenine - folate antagonists therefore prevent the synthesis of normal DNA

Question 8

What is methotrexate? How does it work?

Answer 8

it is an antimetabolite - works by inhibiting the metabolism of folic acid- therefore inhibiting the synthesis of purines in the DNA

Question 9

What do we give in conjunction with methotrexate to ‘rescue’ bone marrow and GI mucosa?

Answer 9

we give folinic acid (leucovorin) to rescue the healthy tissues - allowing them to biosynthesise some purines

Question 10

What is the function of nucleic acid synthesis inhibitors?

Answer 10

They are analogues of purines and pyrimidines - they inhibit enzymes either directly or after formation of a further false compound- so they form a ‘false’ RNA or DNA which is unable or slower to replicate due to extra binding groups

Question 11

What kind of drug is 5-fluorouracil? What is it’s effect?

Answer 11

It is an antimetabolite drug. It is used as an inhibitor of thymidylate synthase by incorporation of it into RNA and DNA.

Question 12

How do Alkylating Agents work against tumors?

Answer 12

they form covalent bonds (on guanine residues) with DNA thereby inhibiting DNA synthesis during S phase and interfering with transcription The main action of these occurs during replication when some parts of DNA are unpaired and therefore more susceptible to alkylation.

Question 13

What type of drug is Cisplatin? What sort of effect does it have on the body?

Answer 13

Cisplatin is an alkylating agent (platinum class) - it binds to and causes cross linking of DNA which ultimately triggers apoptosis

Question 14

How do cytotoxic antibiotics work against tumors?

Answer 14

these are substances of microbial origin which prevent mammalian cell division - they are flat molecules which interpose themselves between the coils of DNA strands and cause inhibition of macromolecular biosynthesis

Question 15

What type of drug is Anthracycline? How does it work?

Answer 15

Anthracycline is a cytotoxic antibiotic - it works by interacting with DNA by intercalation and prevents correct uncoiling and exposure of DNA by stabilising DNA topoisomerase 2 complex (the enzyme which relaxes supercoils in DNA for transcription)

Question 16

What is the adverse effect of Anthracycline?

Answer 16

it produces O2 radicals which are normally inactivated by catalase and glutathione - but there are low levels of catalase in the heart so the heart is vulnerable on this medication

Question 17

How do Vinca Alkaloids prevent tumour proliferation?

Answer 17

they are spindle poisons (vincristine and vinblastine) they act by binding to tubular and inhibiting its polyermerization into microtubules

Question 18

How do taxanes work to prevent tumour proliferation?

Answer 18

They (derived from the yew tree bark) interfere with mitosis by promoting formation of intracellular microtubules and preventing disassembly of formed microtubules during anaphase

Question 19

What is the most common cause of failed chemotherapy?

Answer 19

Drug resistance

Question 20

What are the five mechanisms of drug resistance?

Answer 20

1) decrease in amount of drug taken up by the cell 2) insufficient activation of the drug 3) increased concentration of target enzyme 4) increased utilization of alternative metabolic pathways 5) repair of drug induced lesion

Question 21

What is the cause of multi drug resistance?

Answer 21

a number of things, but mainly from elevated expression of drug transporters (ATP-binding cassette (ABC) transporter proteins)

Question 22

Describe the P-glycoprotein Drug transport molecule and its significance in anti-cancer drugs

Answer 22

it is a membrane transporter that acts as a drug efflux pump - *physiologically it is meant to protect the cells from toxins* - this protein is over expressed in many cancers disallowing for the buildup of chemotherapy drugs.

Question 23

Describe where each cytotoxic drug works in the cell division pathway

Answer 23

a