Lecture 6: Cancer Chemotherapy II Flashcards
What is Multiple Myeloma?
A malignancy of plasma cells
What are 6 characteristics of multiple myeloma?
- Skull x-ray- “punched-out lesions”
- Very painful and usually older patients
- Monoclonal gammopathy
- Bence-Jones proteins in urine (Ab light chains) leading to renal insufficiency
- Bacterial infections due to low IgG production;
- Hypercalcemia
What are 4 key disposing factors of Hepatocellular carcinoma?
- Chronic Hepatitis B
- Chronic Hepatitis C
- Alcoholism
- Aflatoxin exposure (Mold)
What is the environmental cause of Mesothelioma and what can this increase the risk of?
- Asbestos induces mesothelioma directly
- increases the risk of Squamous cell carcinoma in conjunction with cigarette smoking
Mesothelial lining = Outside lining of the lung
Does smoking increase the risk of Mesothelioma?
NO
if you smoke and you get squamous cell carcinoma it does not increase your chance of getting mesothelioma
What are 2 antibiotics used as Chemotherapeutic agents?
Doxorubicin
DNA-bleomycin
What do antibiotics do to act as a chemotherapeutic agent?
Interacts with DNA and disruption of function, intercalates into DNA, inhibits topoisomerases, and generates free radicals to induce their effect
MOA of Doxorubicin as a chemotherapeutic agent (3)
Induces cytotoxicity due to:
- Membrane lipid peroxidation
- DNA-strand breaks
- Direct oxidation of purines and pyrimidines
uses CP450 to create free radicals and cause DNA break
What is a major side effect of doxorubicin/ daunorubicin?
Cardiotoxicity
MOA for bleomycin as a chemotherapeutic agent
causes DNA breaks, used to treat Hodgkin’s disease and testicular cancer, bleomycin-Fe3+ interacts with DNA to cause strand breaks.
creates a complex with oxidized Fe and creates free radicals which causes DNA break
What is a major side effect of Bleomycin?
Pulmonary fibrosis
Which drugs (5) are alkylating agents used as chemotherapeutic agents?
Cyclophosphamide
Carmustine and Lomustine
Decarbazine
Temoxolomide
How do Alkylating agents work as a chemotherapeutic agent? What is a major side effect that they can cause?
- Through Covalent interactions with key cellular component such as DNA, frequently used in combination with other drugs to treat cancers
- They are mutagenic and cause other cancers such as acute leukemia
Cyclophosphamide
1. Therapeutic use
2. MOA
3. Major toxicity
- Therapeutic use: non-Hodgkin’s lymphoma, breast cancer, and sarcomas
- MOA: its modification in the liver via CytochromeP450, to phosphoramide mustard is the major alkylating agent for DNA that is cytotoxic
- Major toxicity: hemorrhagic cystitis
Which alkylating agent(s) crosses the BBB?
Carmustine, Lomustine, Temozolomide
!!CLT CROSSES BBB!!
all used for treatment for brain tumors
temozolomide can also be used for melanoma therapies
Which 2 drugs are nitrosoureas?
Carmustine and Lomustine
Temozolomide is related to ____ and is metabolized into ____
Dacarbazine, MTIC
Dacarbazine
MOA?
Theraputic use?
Cross BBB?
MOA: (MTIC) which induces DNA methylation of guanine residues
Therapeutic use: Melanoma and Hodgkin’s lymphoma
Cross BBB: NOOO
Alkylating agents
What are the therapeutic uses for each?
Mechlororethamine
Melphalan
Busulfan
Chlorambucil
LY
Mechlorethamine- lymphoma treatment
Melphalan- multiple myeloma treatment
Busulfan- CML treatment
Chlorambucil- CLL treatment
LY
What are the microtubule inhibitors used as chemotherapeutic agents?
- Vincristine and Vinblastine
- Paclitaxel and Docetaxel
Vincristine and Vinblastine
–MOA?
–Vincristine therapeutic use
–Vinblastin therapeutic use
–MOA: microtubule depolymerizing drugs that block tumor cell proliferation by interfering with the cell cycle at the M phase.
–Vincristine: ALL, Wilm’s tumor, Ewing’s sarcoma, Hodgkin’s and Non-Hodgkin’s lymphoma
–Vinblastine: Hodgkin’s and Non-Hodgkin’s lymphoma
-stine=depoly
Paclitaxel and Docetaxel
–MOA?
–Paclitaxel therapeutic use (3)
–Docetaxel therapeutic use (4)
–MOA: microtubule stabilizing drugs that block tumor cell proliferation by interfering with the M phase of the cell cycle.
–Paclitaxel: ovarian, breast, and non-small cell lung cancer
–Docetaxel: prostate, breast, GI, and non-small cell lung cancers
Which drug(s) are platinum coordination complexes?
Cisplatin
Cisplatin
MOA?
Therapeutic use?
Side effects?
MOA: binds to guanine in DNA forming inter- and intra strand cross-links, these modifications block both DNA and RNA synthesis
Therapeutic use: used synergistically with radiation and other drugs to treat: ovarian, testicular, and bladder cancer
Side effects: severe nausea and vomiting, nephrotoxicity, ototoxicity
cross-links with strand and outside strand
Which drugs are Topoisomerase Inhibitors?
Topotecan
Etoposide
Topotecan and Etoposide MOA
Topoisomerase Inhibitors
Topoisomerases reduce torsional strain during DNA replication (S PHASE),
Blockade leads to double-strand breaks in DNA, inhibiting DNA replication