CARDIOONCOLOGY

Question 1

evolution of needs for cardio-oncology

Answer 1

• based on the emergence of cardiology problems in cancer patients from cancer drugs
• occurs in up to 1/4 of all cancer patients
• most serious: HF, cardiac dysfunction

Question 2

9 main categories of cardiovascular complications of cancer therapy

Answer 2

1. myocardial dysfunction and heart failure (HF)
2. coronary artery disease (CAD)
3. valvular disease
4. arrhythmias
5. arterial hypertension
6. thromboembolic disease
7. peripheral vascular disease and stroke
8. pulmonary hypertension
9. pericardial complications

Question 3

predicting risk and factors in cardiotoxicity

Answer 3

• cardiac toxicity susceptibility
• predictive biomarkers
• early interventions
• better management
• patient centred studies across the continuum of care
• choose not to treat with X

Question 4

anthracycline toxicity

Answer 4

inter-related molecular mechanisms for cardiotoxic effects (doxorubicin)
1. generation of reactive oxygen species (ROS) and membrane damage
2. inhibition of topoisomerase II-b (TOP2B) and topoisomerase I mitochondrial
3. modulation of intracellular calcium release

Question 5

antineoplastic drugs

Answer 5

classified into type 1 and 2 depending on the chemotherapy-induced toxicity

anthracyclines belong to type 1 agents and cause irreversible and dose-dependent damage which consists of cellular death, either via necrosis or apoptosis

dexrazoxane is the only FDA-approved drug for preventing anthracycline-induced cytotoxicity

Question 6

dexrazoxane moa

Answer 6

• cyclic derivative of EDTA that penetrates cell membranes
• may be converted intracellularly to a ring-opened chelating agent that interferes with iron-mediated free radical generation thought to be responsible for anthracycline induced cardiomyopathy
• dexrazoxane prevents doxorubicin from binding to the Top2-beta-DNA complex by trapping Top2Beta in a closed clamp form, this inhibits the formation of DNA breaks leading to cell damage

Question 7

Herceptin and cardiotoxicity

Answer 7

• cardiac toxicity as a side effect of trastuzumab treatment
• highly effective for EPFR HER2+ breast cancer but is associated with a decline in left ventricular ejection fraction
• a higher cardiac risk when treated in combination with doxorubicin

Question 8

neuregulin

Answer 8

• in the heart, neuregulin (NRG-1) triggers HER-4/HER-4-homo-dimerisation and HER-4/HER-2-heterodimerisation on cardiomyocytes to induce protective pathways in response to stress
• blockade of cardiac HER-2 by Herceptin results in disruption of NEG signalling and results in cardiomyocyte dysfunction and death