Molecular Targets of Cancer Pt. 2 Flashcards
Cancer can develop resistance to chemotherapy via the following mechanism(s). (select all that apply).
By Upregulating apoptosis
By downregulating target enzymes
By downregulating enzymes essential for drug transport
By inhibiting enzymes involved in inactivating biotransformation
By downregulating target enzymes
By downregulating enzymes essential for drug transport
By inhibiting enzymes involved in inactivating biotransformation (SOMETIMES)
List the purine nucleotides
Adenine and Guanine
List the pyrimidine nucleotides
Cytosine, Thymine and Uracil
What is responsible for reducing all ribonucleotides to deoxyribonucleotides?
Ribonucleotide reductase
True or false: 5-Fluorouracil induces DNA synthesis by upregulating biosynthesis of thymidylate
False. 5-FU inhibits DNA synthesis by interfering with the biosynthesis of thymidylate
How does 5-FU exhibit toxicity?
It depletes thymidylate from cancer cells as well as normal cells
6-Mercaptopurine (6-MP), azathioprine (AZA) and thioguanine are structural analogues of what?
Purines
True or false: AZA is a prodrug form of 6-MP
True
What is the major clinical application of 6-MP?
Acute Lymphoblastic Leukemia (ALL)
Hydroxyurea MOA
Inhibits ribonucleotide reductase
Adverse effect of hydroxyurea
Long term use can actually cause cancer (leukemogenic)
DNA alkylators (induce/inhibit) mutagenesis and (induce/inhibit) carcinogenesis
Induce, induce
True or false: Some organometallic agents damage DNA via interstrand cross-linking
True
Describe the mechanism of resistance
Highly reactive drugs can be deactivated by intracellular nucleophiles, like glutathione
Cisplatin use and MOA
Most active drug in treating testicular cancer. Targets nucleophilic centers in guanine, adenine and cytosine
Which conformation of cisplatin exhibits greater antitumor activity?
Cis conformation
True or false: The trans conformation of cisplatin binds covalently to DNA
True
Bleomycin MOA
Binds DNA and chelates iron(II), forming free radicals which cause single and double stranded DNA breaks
List examples of taxanes and their MOA
Paclitaxel, docetaxel, cabazitaxel; inhibit microtubule depolymerization
True or false: The presence of the two chloride leaving groups on Cyclophosphamide allows the alkylating agent to cross-link proteins
False
Long term use of this ribonucleotide reductase inhibitor may be leukemogenic.
a) Gemcitabine
b) Hydroxyurea
c) Cyclophosphamide
d) Carboplatin
Hydroxyurea
True or false: EGF receptor agonists are a class of drugs used in the to block a pathway that drives cancer growth
False. EGF receptor antagonists
Adverse effects of EGFR antagonists
Skin rash and diarrhea
Oncogenic mutation of ____ is found in approximately 30% of human cancers
Ras
True or false: Solid tumors require development of a neovasculature in order to sustain growth and survive conditions of hypoxia
True
