anti-cancer drugs

what are the three modalities for treating malignant tumors?

drug therapy, surgery, radiation

which tumors cannot be surgically excised?

leukemia and lymphoma

which drugs treat leukeimia and lymphoma?

antineoplastic drugs

biggest obstacle of chemotherapy:

toxicity to normal cells (lack of selectivity)

which cells are most effected by chemotherapy (besides the cancer cells)?

cells that rapidly divide, bone marrow RBCs

chemo affecting the bone barrow:

myelosuppresion

myelosuppresion due to chemotherapy can lead to:

leukopenia, thrombocytopenia, anemia

principle early sign of leukemia

fever

signs of thrombocytopenia:

increased risk of bleeding, easily bruised

signs of anemia:

fatigue, lethargy, feeling tired

what other cells are effected due to antineoplastic drugs?

gastrointestinal epithelium, leads to stomatitis, muscositis, diarrhea, nausea/vomiting

hair follicles --> alopecia

other obstacles to chemotherapy:

- high tumor burden at the time of dx --> limited success rate

- anticancer drug resistance

- allowing normal cells to recover

intermittent chemotherapy only works if:

normal cells repopulate faster than malignant cells

is someone has a high tumor burden at the time of diagnosis they are more likely to ______, how does this affect treatment?

have metastasis, could be less responsive to anticancer drugs due to slower growth rate

which phase represents a resting phase when cells are not actively dividing or growing?

G0

anticancer drugs are more toxic to ________ cells than to _______ cells

cycling, resting

two categories of antineoplastic drugs:

cytotoxic agents, targeted anticancer drugs

which kind of drugs affect a specific point in the cell cycle?

cell cycle-specific cytotoxic agents

which drugs are more specific to cancer cells?

targeted anticancer drugs

which drugs kill cancer cells throughout the cell-cycle at anytime?

cell cycle-nonspecific cytotoxic agents

MOA of DNA alkylating drugs:

cross link DNA by covalently binding to the nitrogenous bases (guanine in particular), thus DNA cannot separate for cell division

most common DNA alkylating drugs:

nitrogen mustards

how did the clinical use of nitrogen mustards come about?

recognized bone marrow suppression/lymph node shrinkage in soldiers exposed to mustard gas (WWI)

what is one of the most widely used nitrogen mustards? what kind of tumors do they treat?

cyclophosphamide/Ifosfamide

major toxicity of cyclophosphamide/ifosfamide:

myelosuppression, hair loss, n/v, hemorrhagic cystitis

which symptom is unique to cyclophosphamide/ifosfamide:

hemorrhagic cystitis, can lead to bladder cancer/leukemia as well

common side effects of chlorambucil, mechlorethamine, melphalan: which drug class are they?

myelosuppression, N/V, DNA alkylating nitrogen mustards

which DNA alkylating nitrogen mustards can cross the BBB?

nitrosoureas

what is a unique side effect to nitrosoureas?

pulmonary fibrosis (scarring in lungs/chest)

cisplatin, carboplatin and oxaliplatin are all:

DNA alkylating agents, Platinum compounds

major toxicities that are unique to cisplatin, carboplatin, and oxaliplatin:

nephrotoxicity

which drugs are used alongside platinum compounds to help neutralize the nephrotoxicity?

mannitol, sodium thiosulfate

which side affect is unique to busulfan? what kind of drug is it?

pulmonary fibrosis, DNA alkylating agent

unique side effect to mitomycin, what kind of drug is it?

pulmonary fibrosis, nephrotoxicity

most chemo drugs are:

infusions

what are the two types of anticancer drug resistance?

innate and acquired

what is one of the most common mechanisms of drug resistance in chemotherapy?

drug efflux pumps (P-glycoprotein pump)

MOA of DNA intercalating drugs:

wedge between bases along the DNA impairing DNA synthesis/replication (break strands)

examples of DNA intercalating agents

anthrocyclines, bleomycin, dactinomycin, etoposide/teniposide

Which drugs belong to anthrocyclines:

doxorubicin, daunorubicin, idarubicin

what are the few cancer drugs that can cause cardiotoxicity (sinus tachycardia, cardiomyopathy)

anthrocyclines

which drug can help minimize cardiotoxicity?

dexrazoxane

Which drug belongs to the DNA intercalating agents and can cause pulmonary toxicity and mucotaneous toxicity?

bleomycin

blemoycin is know for its:

pulomonary toxicity and mucocutaneous toxicity

Which drug belongs to the DNA intercalating agents and is used to treat pediatric tumors?

dactinomycin

Which drug belongs to the DNA intercalating agents have less pronounced side effects compared to anticancer drugs (besides mild N/V and alopecia)?

etoposide and teniposide

Which anti-cancer drugs work by inhibiting enzymes that catalyze various steps in DNA synthesis during the S phase?

DNA synthesis inhibitors

Which DNA synthesis inhibitor works by inhibiting the enzyme dihydrofolate reductase which converts folate to dTMP? this does what to the cancer cells DNA?

Methotrexate, decreases thymine levels

toxic effects of methotrexate:

hepatotoxicity

which drug can be administered with methotrexate to help prevent stomatitis and myelosuppression?

leucovorin

which DNA synthesis inhibitor works by inhibiting thymidylate synthetase? which drug is it often administered with?

pemetrexed, cisplatin

most common side effect of pemetrexed:

myelosuppression

Which DNA synthesis inhibitors are purine analogs and are converted into nucleotides and then incorporated into the cancer cells DNA?

mercaptopurine and thioguanine

mercarptopurine and thioguanine can contribute to:

the development of other cancers and hepatotoxicity

which DNA synthesis inhibitors are pyrimidine analogs that are incorporated into the DNA causing termination of synthesis?

cytarabine and 5-Fluorouracil

5-Fluorouracil inhibits:

thymidylate synthetase

side effects of cytarabine and 5-FU

n/v, myelosuppression, oral and GI ulceration

which DNA synthesis inhibitor is a cytosine analog that takes the place of cytosine by incorporating into the DNA chain and eventually breaks the strands?

gemcitabine

toxicities of gemcitabine:

myelosuppresion, alopecia, n/v

which cancer drugs are miotic inhibitors?

vinca alkaloids, taxanes

vinka alkaloids inhibit:

assembly of microtubules

taxanes inhibit:

disassembly of microtubules

which drugs are vinka alkaloids?

vincristine, vinblastine

side effects of vincristine

neurotoxicity, loss of DTRs, paresthesias of fingers/toes, autonomic neuropathies

side effects of vinblastine:

myelosuppresion

list the taxanes that inhibit disassembly of microtubules in cancer cells:

paclitaxel, docetaxel, cabazitaxel

side effects of cabazitaxel

neurotoxicity

MOA of targeted anticancer drugs

inhibit specific proteins involved in tumor cell growth

major types of target anticancer drugs:

protein kinase inhibitors, monoclonal antibodies, immune therapies, endocrine therapies

imatinib is an example of a:

protein kinase inhibitor

which enzyme does imatinib inhibit? what does this result in?

deregulated bcr-abl tyrosine kinase, stops leukemic cell proliferation

the BCR-ABL is what kind of mutation? what does it cause?

translocation, constantly drives leukemic cell proliferation

MOA of monoclonal antibodies:

find cancer-cell specific antigens and grow antibodies against it and then use those antibodies to attack and kill cancer cells

examples of monoclonal antibodies:

bevacizumab, cetuximab, trastuzaumab

which monoclonal antibody is for vascular endothelial growth factor and acts as an angiogenesis inhibitor?

bevacizumab

which monoclonal antibody is for the epidermal growth factor receptor (EGFR)?

cetuximab

which monoclonal antibody is for the human epiderman growth factor-2 (HER2/neu) receptor?

trastuzumab

MOA of immune therapies:

harness the immune system, not very effective

MOA of aldesleukin

immune therapy that promotes B and T cell proliferation used for metastatic renal cell carcinoma

MOA of IFN alfa-2b

immune therapy that increases the activity of cytotoxic cells of the immune system

What kind of cancer are endocrine therapies effective for?

cancers from tissue whos growth are under gonadal hormone control, breast/prostate/endometrial cancers

Examples of endocrine therapies:

estrogen receptor antagonists, aromatase inhibitors, GnRH agonists/Androgen receptor antagonists

tamoxifen is an:

estrogen receptor antagonist used for ER+ breast cancer

anastrazole and letrozole are:

Aromatase inhibitors used for ER+ breast cancer in post-menopausal women

examples of GnRH agonists and Androgen receptor antagonists

leuprolide and flutamide

how does leuprolide work:

- initially increases production of hormones (agonist)

- eventually decreases secretion of LH and FSH --> decreased production of estrogen and testosterone

which drug is given alongside leuprolide to block the initial surge of testosterone in the 1st week of treatment acting as an antagonist?

flutamide