Cancer Therapy

Question 1

Tamoxifen

Answer 1

• Breast Cancer
• selective estrogen receptor modulator (SERM)
• prodrug
• MOA: mixed estrogenic & anti-estrogenic activity at estrogen receptors (ER)
• breast-located ER: predominantly anti-estrogenic effects / blocks Estrogen-R. → reduced transcription of ER responsive genes → weniger Zellteilungsaktivität im Bestrogen-abhängigen Gewebe
• Problem: first CYP3A4, then CYP2D6 abhängig zum aktiven Metabolit: 2D6-Polymorphisms!

Question 2

PI3-Kinase Inhibitors

Answer 2

Targeted Therapy in Cancer

Physiology:
Phosphoinositide 3 kinases (PI3Ks):
intracellular signal transducer enzymes = Schlüsselenzym des PI3K/AKT/mTOR-Signalwegs,
crucial for the regulation of cellular growth, differentiation, and survival
- verwickelt in the sensitivity of cancer cells to insulin, IGF-1 and calorie restriction

PI3K: mutated in many cancers → PI3K activity significantly contributes to cancer development & progression

Question 3

Immune Checkpoints Antibodies

Answer 3

Immunotherapy in Cancer
idea: antibodies bind to tumor antigens = marking the cancer cells for the immune system to kill
- monoclonal antibodies against CD52, CD20, immune checkpoints
(blockade of negative feedback signalling to immune cells → enhanced immune response against tumor cells)

Beispiele

• CTLA-4-Inhibitoren (cytotoxic T-lymphocyte-associated protein 4 (CTLA-4))
• PD-1-Inhibitoren (programmed cell death 1 protein (PD-1))
• PD-L1-Inhibitoren (PD-1 ligand (= PD-L1))