Cancer Chemotherapy

What protein regulates the cell cycle?

p53

Where is the cell cycle regulated?

two checkpoints:

one before replication

one before mitosis

What are cytotoxic drugs (kills cells) used in cancer?

alkylating agents

anti-metabolites

antibiotics

What are examples of alkylating agents?

Cyclophosphamide (Cytoxan)

Carmustine (Gildadel Wafer)

Cisplatin (Platinol)

What is the MOA of Alkylating Agents?

alkylate DNA to form DNA crosslinks, resulting in cell death

What drug class are Cyclophosphamide (Cytoxan), Carmustine (Gildadel Wafer), and Cisplatin (Platinol) in?

alkylating agents

What are side effects of Cyclophosphamide (Cytoxan)?

bladder toxicity

hemorrhagic cystitis

immune suppression

hair loss

N/V

What is Carmustine (Gildadel Wafer) used for? Why?

brain tumors because it is very lipid soluble and can cross BBB

What are the additional side effects of Cisplatin (Platinol)?

nephrotoxicity

ototoxicity

What are examples of anti-metabolites?

Methotrexate (Trexall)

Flurouracil (Adrucil)

6-Mercaptopurine (Purixan)

What type of drug are Methotrexate (Trexall), Flurouracil (Adrucil), and 6-Mercaptopurine (Purixan)?

anti-metabolites

What is the MOA of methotrexate (trexall)?

inhibits synthesis of tetrahydrofolate

How can we reverse the effects of methotrexate?

Leucovorin (folinic acid)

What is the MOA of 5-fluorouracil?

binds thymidylate synthase therefore interferes with RNA + mRNA

What is the MOA of 6-mercaptopurine?

inhibits purine nucleotide synthesis

What are examples of natural product cancer chemotherapy drugs?

Vinblastine (Velman)

Paclitaxel (Taxol)

Etoposide (Toposar)

Irinotecan (Camptosar)

What is the MOA of Vinblastine (Velman)?

inhibits tubule polymerization (prevents microtubule assembly) therefore stopping cell division

What is the MOA of Paclitaxel (Taxol)?

prevents disassembly of microtubules therefore cell gets stuck in mitosis and dies

What is the MOA of Etoposide (Toposar)?

inhibits topoisomerase II, causing DNA strands to break

Wha is the MOA of Irinotecan (Camptosar)?

inhibits topoisomerase 1 therefore inhibiting replication and transcription

What are examples of anti-tumor antibiotics?

Doxorubicin (Adriamycin)

Bleomycin (Blenoxane)

Mitomycin (Mutamycin)

What drug class are Doxorubicin (Adriamycin), Bleomycin (Blenoxane), and Mitomycin (Mutamycin) in?

anti-tumor antibiotics

What is the MOA of Doxorubicin (Adriamycin)??

cross links DNA and inhibits topoisomerase II

What is a side effect of Doxorubicin (Adriamycin)?

cardiotoxicity

What is the MOA of Bleomycin (Blenoxane)??

breaks DNA strands

What is a side effect of Bleomycin (Blenoxane)?

pulmonary fibrosis

What is the MOA of Mitomycin (Mutamycin)?

DNA crosslinker

What are examples of antibodies used to treat cancer?

Alemtuzumab (Lemtrada)

Pembrolizumab (Keytruda)

Nivolumab (Opdivo)

What class of drugs are Alemtuzumab (Lemtrada), Pembrolizumab (Keytruda), and Nivolumab (Opdivo)?

monoclonal antibodies used to treat cancer

What is the MOA of Alemtuzumab (Lemtrada)?

binds CD52 on B cell, killing it

What is Alemtuzumab (Lemtrada) used to treat?

B-cell leukemia (B-CLL)

What are examples of anti-PDL-1 agents?

Pembrolizumab (Keytruda)

Nivolumab (Opdivo)

What is the MOA of Pembrolizumab (Keytruda) and Nivolumab (Opdivo)?

inhibit PLD-1 on tumor cells so that they cannot suppress human T cells

What kind of drugs is Imatinib (Gleevec)?

Tyrosine Kinase inhibitor

What is the MOA of Imatinib (Gleevec)?

prevents phosphorylation

What is Imatinib (Gleevec) used to treat?/

Chronic myelogenous leukemia

What is a side effect of Imatinib (Gleevec)??

metabolized by CYP, DDI and avoid grapefruit

How do cancer cells gain resistance to drugs?

mutations

What are the general side effects of cancer chemotherapy?

bone marrow toxicity --> decreased WBCs and platelets, increased risk for infections and bleeding

N/V

hair loss

Side effect of high dose of methotrexate?

nephrotoxic