Anti-Cancer Drugs: Signal Transduction Inhibitors Flashcards Preview

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Flashcards in Anti-Cancer Drugs: Signal Transduction Inhibitors Deck (14):
1

Signal Transduction Inhibitors includes?

1. Inhibitors of EGFR (ErbB1) and HER2/neu (ErbB2)
2. Inhibitors of BCR-ABL and C-KIT
3. Inhibitors of RAS/MAP kinase pathways
4. Proteasome Inhibitors
5. Angiogenesis Inhibitors

2

What is signal transduction?

Transmission of molecular signals from a cell's exterior to its interior
--signals received by cells must be transmitted effectively into the cell to ensure an appropriate response

3

Protein kinases are critical components of signal transduction pathways that regulate cell growth and adaptation to the extracellular environment. Protein Kinases can be classified into what?

1. Tyrosine Kinases: Phosphorylate Tyrosine Residues
2. Serine and Threonine Kinases: Phosphorylate Serine and Threonine Residues
3. Kinases with activity toward all three residues

4

What are the drugs for Inhibitors of EGFR (ErbB1) and HER2/neu (ErbB2)?

1. Gefitinib: Inhibitor of the EGFR tyrosine kinase (non small cell lung cancer)
2. Erlotinib: inhibitor of the EGFR tyrosine kinase (non small cell lung cancer and carcinoma of the pancreas)
3. Lapatinib: Inhibitor of EGFR and ErbB2 (non small cell lung cancer and carcinoma of the pancreas)
4. Cetuximab: Monoclonal Antibody Against EGFR. (Colorectal cancer -- restricted to patients with tumors expressing wild type KRAS)
5. Trastuzumab: Monoclonal Antibody Against ErB (HER2)(cardiotoxic)(breast cancer with HER2 overexpression)

5

What are the drugs for Inhibitors of BCR-ABL and c-KIT?

Imatinib: Inhibits the Bcr-Abl tyrosine kinase and Inhibits c-kit (receptor for tyrosine kinase)
CML, Kit positive GI stromal tumor and Idiopathic hypereosinophilic syndrome

6

What are the drugs for Inhibitors of RAS/MAP kinase pathways?

Sorafenib: inhibits the RAF serine/threonine kinase and Inhibits VEGF-R2 and VEGF-R3 and PDGFR-B
Renal Cell Carcinoma

7

What are the proteasome Inhibitors?

Bortezomib: Induces growth inhibition and apoptosis of tumor cells
Multiple Myeloma and Mantle Cell Lymphoma

8

What are the Angiogenesis Inhibitors?

Sunitinib: Inhibits VEGFR-1, VEGFR-2 and PDGFR
Renal Cell Carcinoma
GI stromal tumor

9

The last drugs are the Miscellaneous Agents: Asparaginase, Hydroxyurea, Interferon alpha. First lets start with Asparaginase, what is the MOA?

Hydrolyzes circulating L-asparagine to aspartic acid and ammonia
Tumor cells in ALL lack asparagine synthase, so they require an exogenous source of L-asparagine. Thus depletion of L-asparagine results in effective inhibition of protein synthesis.

10

What are the clinical application and AE of Asparaginase?

Clinical:
--Childhood Acute Lymphobalstic Leukemia (ALL)
AE:
--Hypersensitivity, decrease in clotting factors, liver abnormalities, pancreatitis and seizures

11

The second miscellaneous agent is Hydroxyurea, what is the MOA?

Inhibits ribonucleotide reductase which converts ribonucleoside diphosphate to deoxyribonucleoside diphosphate
---depletion of deoxyribonucleosides trisphosphate pool thereby inhibiting DNA synthesis
--kills cells in S phase

12

What are the clinical applications and Adverse effects of Hydroxyurea?

Clinical:
Malignant melanoma, chronic myelocytic leukemia, ovarian cancer, primary squamous cell carcinoma of the head and neck, excluding the lip
Used to tx adult sickle cell disease
AE:
--Myelosuppression

13

Last Miscellaneous drug is Interferon Alpha. What is the MOA?

MOA:
---stimulates natural killer cells to kill the transformed cells
--increases the expression of HLA molecules on tumor cells

14

What are the clinical applications and AE for Interferon Alpha?

Clinical:
--Kaposi Sarcoma
--Hairy Cell Leukemia
---Renal Cell Carcinoma
--Antiviral Activity Against HPV, HBV and HCV
AE:
--Flu like symptoms

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