Lecture 20 - Antitumor Agents Flashcards
How do vinca alkaloids ihibit microtubules?
Vinca alkaloids inhibit microtubule polymerization
How do taxanes stabilize microtubules?
Taxanes stabilize microtubules by promoting their elongation by preventing the removal of tubulin dimers
How do alkylating agents cause cell death?
Alkylating agents add an alkyl group to the guanine base of the DNA molecule which can cause intrastrand linking and cross-linking leading to breaks in the DNA strand, inability of the cell to multiply, and eventually death
What are antimetabolites?
Can refer to any drug that interferes with metabolic pathways by inhibiting enzymatic reactions
What do antimetabolites usually affect?
- Inhibit enxymes that are essential to the synthesis of DNA and RNA (enzymes involved with purines, pyrimidines, and folic acid)
- Cell-cycle phase specific inhibition (S phase)
What cells are most vulnerable to the cytotoxic effects of cell-cycle phase non-specific agents?
Resting cells (phase G0) - effective for slow-growing tumors
List S phase specific drugs
- Cytosine arabinoside
- Hydroxyurea
List S phase specific self-limiting drugs
- 6-mercaptopurine
- Methotrexate
List M phase specific drugs
- Vincristine
- Vinblastine
- Paclitaxel
List cell cycle non-specific drugs
- Alkylating drugs
- Nitrosoureas
- Antitumor antibiotics (mitoxantrone, bleomycin)
- Procarbazine
- Cisplatin
- Decarbazine
How do antitumor antibiotics prevent proliferation?
They bind with DNA to prevent RNA synthesis and cause the DNA to uncoil
How does Bleomycin cause DNA to uncoil?
It binds to the double helix and exposes nucleotides to the iron (II) atom which generates oxygen species that cause single- and double-strand breaks by a free radical mechanism
Why does chemotherapy come with so many severe side effects?
Chemotherapy drugs target processes that cancer cells need to grow and divide, but they also damage healthy cells
What are some types of Targeted Therapies?
- Hormone therapies
- Signal transduction inhibitors
- Angiogensis inhibitors
- Immunotherapies
- Using monoclonal antibodies to deliver toxic molecules
- Immune checkpoint inhibitors
- Deliver bacterial toxins to inhibit protein translation
How do hormone therapies slow or stop hormone-sensitive tumors?
Prevent the body from producing the hormones or interfering with the action of the hormones required by the tumor
Estrogen receptor modulators
- Used in the treatment of breast cancer
- Tamoxifen, Raloxifene, Toremifene
What are Selective Estrogen Receptor Modulators (SERMs)?
A class of compounds that interact with estrogen receptors in a tissue-selective manner
- Tamoxifen and Raloxifene: lowers breast cancer risk, preserves bone mineral density
- Used in prevention of breast cancer, osteoporosis, and menopausal symptoms
Aromatase inhibitors
Block estrogen synthesis
- Anastrozole, letrozole, exemestane
Drugs affecting gonadotropin-releasing hormone (GnRH)
Inhibit production of estrogen, progesterone, and testosterone
- Used in treatment of prostate cancer and advanced breast and ovarian cancer
- Leuprolide, goserelin, nafarelin, and triptorelin (GnRH analog)
Androgen antagonists
Used in treatment of prostate cancer
- Flutamide, bicalutamide, and nilutamide
Tamoxifen - Mechanism of action
Acts as an estrogen antagonist in breast tissue inhibiting the growth of estrogen0dependent breast cancer cells while acting as an agonist in uterus and bone to help prevent osteoporosis
Imatinib (Gleevec)
Tyrosine kinase inhibitor that targets the BCR-ABL kinase preventing chronic myeloid leukemia
What are growth factors?
Proteins similar to hormones which regulate survival, proliferation, migration, and differentiation and can be produced by many different types of tissue
- NGF, VEGF, PDGR, EGF, IGF
What is a receptor tyrosine kinase (RTK)?
Membrane bound receptors that respond to different growth factors and activate various signaling cascades
- Common anti-cancer drug targets
- Over 50 identified
