DNA Intercalating Agents

Question 1

Name the 5 anthracycline antibiotics. What major mechanistic class do they belong to?

Answer 1

Daunorubicin, doxorubicin, epirubicin, idarubicin, and mitoxantrone. DNA intercalating agents.

Question 2

Name the 2 DNA intercalating agents that are not anthracyclines.

Answer 2

Dactinomycin/Actinomycin D and Bleomycin

Question 3

Name the DNA intercalating agent that interferes with DNA-dependent RNA polymerase by intercalating G-C pairs.

Answer 3

Dactinomycin/Actinomycin D

Question 4

Name the DNA intercalating agent that is derived from copper-chelating peptides and can induce both single- and double-stranded DNA breaks.

Answer 4

Bleomycin

Question 5

From what microbe were the DNA intercalating agents derived?

Answer 5

Streptomyces

Question 6

What is the common MO for all the “anti-tumor antibiotics”, and are they cell cycle specific?

Answer 6

DNA intercalating, CCNS

Question 7

Describe 3 ways DNA intercalating agents fight cancer, without using the word “intercalate”

Answer 7

block DNA/RNA synthesis, cause DNA strand breaks, and interfere with cell replication

Question 8

What DNA intercalating agent is used to treat pediatric tumors like Wilms’ tumor, rhabdomyosarcoma, and Ewing’s sarcoma, as well as choriocarcinoma (placenta)?

Answer 8

Dactinomycin/Actinomycin D

Question 9

What is a major side effect of treating pediatric tumors with dactinomycin?

Answer 9

Hematopoietic suppression with pancytopenia

Question 10

Daunorubicin, doxorubicin/adriamycin, epirubicin, and idarubicin all have what major side effect, and what drug can protect against this effect?

Answer 10

Cardiotoxicity; dexrazoxane is cardio-protective

Question 11

What 2 anthracyclines are used only to treat AML?

Answer 11

Daunorubicin and idarubicin

Question 12

Which anthracycline has the broadest spectrum of clinical use, including for sarcomas, breast and lung carcinomas, and malignant lymphomas?

Answer 12

Doxorubicin

Question 13

What 2 cancers is epirubicin used to treat?

Answer 13

Metastatic breast cancer and gastric cancer

Question 14

Name the DNA intercalating anthracycline that has the least cardiotoxicity.

Answer 14

Mitoxantrone

Question 15

Epirubicin is used in the combo regimen FEC to treat what kind of cancer?

Answer 15

Breast cancer (metastatic)

Question 16

What 2 diseeases is mitoxantrone used to treat?

Answer 16

AML and late-stage multiple sclerosis

Question 17

Besides intercalation, what is another mechanism by which the anthracyclines cause DNA damage?

Answer 17

They donate electrons to oxygen, forming ROS (reactive oxygen species) like superoxide, hydrogen peroxide, and hydroxyl radicals

Question 18

What are 3 characterically toxic side effects of bleomycin?

Answer 18

Pulmonary toxicity (fibrosis), cutaneous toxicity (hyperpigmentation, hyperkeratosis, erythema), and hyperthermia

Question 19

In which DNA intercalating agent is myelo- and immunosuppression the least pronounced, making it a good drug to use in combination regimes like PEB and ABVD?

Answer 19

Bleomycin

Question 20

Name 3 types of cancer that bleomycin is often used to treat, and the combination regimens associated with 2 of those cancers.

Answer 20

Testicular tumor (PEB), Hodgkins lymphoma (ABVD), and squamous cell carcinoma