suicide pact?????

formula for BSA

use total body weight

Which of the following structures can serve as an intermediate in the activation of nitrogen mustards?

(tell me what the intermediate is and what to look for)

aziridinium (look for triangle)

Mustargen is a potent vesicant. In case of accidental skin contact, which of the following solutions should be applied? AND WHY

2% sodium thiosulfate solution;

bc it makes it water soluble so it can be washed off the skin

sodium thiosulfate MOA

reacts with mustargen to make inactive, highly ionized, water soluble ester that can be washed off

ifex can form what toxic metabolite(s)

acrolein

chloroacetaldehyde

temozolomide is converted to the active metabolite _____

MTIC

AZT MOA

incorporated into RNA to decrease tRNA methyltransderase, leads to inhibited methylation and then apoptosis

cyclophosphamide undergoes ______ via _____ to form what three metabolites?

C-4 hydroxylation via CYP2B6 

acrolein, phosphoramide mustard, and carbolamine

Chlorambucil undergoes ____ to form active ________

beta-oxidation rxn; phenylacetic acid mustard

The _______of guanine reacts with the ___ of Lurbinectedin to form an adduct

N2 of the minor groove; iminium intermediate

Which reactive species does Carmustine generate in situ to interact with DNA?

Vinyl cation and isocyanate

6MPMP:

1. what does it stand for

2. function

2. what drugs are CI with it and why

1. 6-thioinosinate or 6-methylthioinosinate

2. inhibits the first step of purine synthesis and the conversion of inosinic acid to xanthylic acid

3. xanthine oxidase inhibitors because they inhibit the enzyme that metabolizes it so it stays in the body unmetabolized

toxic effects of acrolein include…

hemorrhagic cystitis and bone marrow suppression

how does Mesna treat acrolein exposure

given before chemotherapy with Cytotoxan or Ifex

neutralizes metabolites by binding to -SH (sulfhydryl) moieties

increases urinary excretion of cysteine

lurbinectedin:

MOA

covalently binds to N2 of guanine minor groove to alkylate it

inhibits RNA polymerase II

how does lurbinectedin exert its alkylating effects

by its iminium intermediate

DOX MOA:

1. intercalation leads to ____ due to topo II inhibition

2. produces ______ that lead to cellular DNA damage and cardiotoxicity

3. can be reduced to a _____ by CYP450, which can lead to…

1. single or double strand DNA breaks

2. reactive oxygen species

3. semiquinone radical; reaction with oxygen —> make a superoxide radical —> form hydrogen peroxide and a hydroxyl radical

taxanes MOA

prevent mitosis by altering normal MT organization, preventing proper dissolution of spindles leading to cell cycle arrest

paclitaxel:

1. class

2. solubility

1. taxane MT targeting agent

2. highly lipophilic and poorly water soluble

docetaxel:

1. class

2. formulation

1. MT targeting taxane

2. must be strategized to improve solubility

How is docetaxel structurally different from paclitaxel?

Modifications increase tubulin binding affinity

What functional group allows vinca alkaloids to form water-soluble salts?

tertiary amine

What is the mechanism of vinca alkaloids? and what is the result?

Inhibit microtubule polymerization; Prevent mitotic spindle formation → mitotic arrest

What enzyme do epipodophyllotoxins inhibit? and what is their MOA?

(etoposide for example)

Topoisomerase II

Stabilize DNA–topoisomerase complex → prevent DNA religation —> DNA fragmentation —> cell death

SERMs:

1. MOA

2. exhibit ____ dependent activity

1. Modulate estrogen receptor signaling

2. tissue

Aromatase MOA

converts androgens to estrogens

aromatase inhibitors MOA

reduces circulating estrogen levels sometimes by mimicking the natural substrate

exemestane:

1. structure and class

2. reversible or irreversible enzyme inhibition?

3. requires consideration of the pts ____

1. steroidal aromatase inhibitor

2. irreversible

3. hormonal status

kinase inhibitors:

1. what do they mimic?

2. where do they bind and how?

3. what determines selectivity adn potency?

1. ATP binding

2. Hinge regions via hydrogen bonding

3. structural features

MOA:

1. type I tyrosine kinase inhibitors

2. type II tyrosine kinase inhibitors

1. bind to the active kinase conformation at the ATP binding site

2. target the inactive DFG out conformation, exposing an adjacent hydrophobic pocket

dexrazoxane:

1. what is it?

2. what it do?

1. iron chelating agent

2. reduce anthracycline associated cardiotox; limit free radical formation through metal chelation

Leucovorin:

1. when is it used?

2. what does it do?

3. structure / formulation

1. Rescue therapy after antimetabolites

1. Restores normal folate pathways

2. Racemic mixture with active L-isomer

why is platinum used?

electrophile that forms a VERY stable covalent bond with the DNA

idk

WHY does pomalidomide (thalidomide analog) has enhanced potency and improved pharmacological properties?

additional amino group on the 4th carbon of the phthaloyl ring

therapeutic vax stimulate ______ of tumor antigens

immune recognition

immunotherapy definition

using the patient's immune system to fight cancer

ability to activate the immune system and destroy cancer cells

what is the primary defense against cancer

immune system

define innate immunity

first response

does not increase or change in response to repeated exposure

non specific

define adaptive immunity

slower and antigen specific response

consists of B and T cells

increased immunity on repeated antigen exposure

creates long term memory

activation of naiive T cells will not occur in the absence of ____

costimulation

deletion of T cells that react strongly with self

negative selection

behavior of cells that have survived negative selection

interact weakly with antigens and fail to become activated

decreased response

immunotherapy approaches

1. specific and active

2. specific and passive

3. non specific and active

4. non specific and passive

specific and active immunotherapy approach example

vaccines that include long lasting memory and immunity

specific and passive immunotherapy approach examples

monoclonal antibodies and T cell based therapy

includes herceptin and mebtera

nonspecific and active immunotherapy approache examples

bacterial products and biological response modifiers (cytokines)

nonspecific and passive immunotherapy approach examples

LAK (lymphokine activated killer cells) and TIL (tumor infiltrating lymphocytes)

autologous vaccine definition

vaccine created by removing tumor cells from the patient's own body

allogenic vaccine definition

vaccine created by removing tumor cells from someone other than the patient

dendritic cell vaccines description

vaccine in which dendritic cells are generated outside that body that, through gene therapy, are able to recognize antigens

antigen vaccines description

peptide vaccines that are specific for one epitope

anti-idiotype vaccines description

vaccines that are antibodies

cause a patient to elicit an immune response after injection into the cancer

DNA vaccines description

vaccine that introduces a tumor gene

antigens are made on a continuous basis

CAR T cell therapy description

engineered molecules that can be introduced into T cells to enable them to target specific tumor antigens

T cells are removed, components are added, then programmed T cells are returned to the patient

website for searching ongoing clinical trials

go to home page at NIH then access clinicaltrials.gove

name the alkylating agents subgroups

nitrogen mustards

nitrosoureas

alkyl sulfonates

triazanes

platinum compounds

examples of nitrogen mustards

cytoxan

ifex

melphalan

chlorambucil

cytoxan is a nitrogen mustard AND an ____

immunosuppressant

nitrogen mustard MOA

forms reactive intermediate that attacks N7 of guanine to cause inter and intra strand cross links resulting in DNA strand breakage and inhibition of replication and transcription

cytoxan toxicity

hemorrhagic cystitis

nitrogen mustard toxicity

bone marrow suppression

N/V

alopecia

infertility

name a nitrosourea

carmustine

what makes carmustine / nitrosoureas unique

cross BBB

carmustine toxicity

delayed bone marrow suppression

name an alkyl sulfonate

busulfan

busulfan toxicity

tonic clonic seizures

dose limited bone marrow depression

triazene examples

dacarbazine

darcarbazine MOA

decompose spontaneously and methylate the N7 and O6 positions of G in DNA

how is resistance to alkylating agents developed?

quickly, the cancer cells increase the amount of repair proteins

what website can you find updates of clinical trials on?

clinicaltrials.gov

immunotherapy definition

activation of the immune system to destroy cancer cells using the pts immune system to fight cancer

RF of breast cancer for women (4)

***on test 3, select all that apply***

extended length of hormone exposure

getting period before 13 yrs old

starting menopause after 55 yo

nulliparity (not having kids)

what things can increase the risk of BC? (3)

***on test 3***

ionizing radiation

increased BMI (in postmenopausal women)

lifestyle choices

name 3 things that can decrease the risk of BC

***on test 3***

breast feeding

exercise

increased BMI (premenopausal)

when should the following age ranges have mammogram screening if they are asymptomatic for BC?

1. ages 40-44

2. ages 45-54

3. ages 55+ AND have 10+ yr life expectancy

1. optional

2. yearly

3. every 2 years

a 52 yo woman comes into the clinic and has average risk for all cancers, which of the following screenign can she have done today?

a. self breast exam

b. mammogram

c. chest X ray

d. low dose helical CT

e. colonoscopy

b and e

(self exams are not reccomended, does not meet requirements for either a chest x ray or a low dose helical CT)

is it recommended to get a yearly breast exam?

nah

pts who DO NOT HAVE BC, but are high risk for developing it should be started on what preventative measure?

endocrine therapy

endocrine therapy is given to prevent BC in high risk pts.

1. what is the drug of choice for premenopausal pts

2. what are the options for post menopausal pts

1. tamoxifen

2. tamoxifen, raloxifene, aromatase inhibitor

how long should a pt be on endocrine therapy if they DO NOT have BC but are at high risk?

5 yrs

What receptor statuses are assessed in nonmetastatic breast cancer diagnosis?

Hormone receptors (estrogen/progesterone), HER2/neu, BRCA1/2 germline

TX for Ductal Carinoma in Situ:

local treatment options

lumpectomy and XRT

TX for Ductal Carinoma in Situ:

if the pt had a lumpectomy or XRT and is ER+, they should then be started on _____ (drug) if they are premenopausal for _____ (duration)

tamoxifen x 5 yrs

TX for Ductal Carinoma in Situ:

if the pt had a lumpectomy or XRT and is ER+, they should then be started on _____ (drug) if they are postmenopausal for _____ (duration)

tamoxifen or aromatase inhibitor

5 years

what are the systemic therapy options for non metastatic BC

endocrine

chemo

biologic

immuno

what immunotherapy agent is indicated for non-metastatic BC

pembrolizumab

what chemotherapy agents are indicated for non metastatic BC

anthracyclines (DOX)

carboplatin

cyclophosphamide

taxanes

pts with high risk BC qualify for…

chemotherapy

what is considered high risk diseases when it comes to BC?

When do HR+/HER2− patients get chemotherapy?

1. pts with HR+ / HER2 - with high risk of relapse (based on additional testing)

2. HER2+

3. HR- and HER2- (triple negative)

a pt is triple negative, what treatment would you reccomend

a. TCH

b. TCHP

c. TH

d. TC

***on test***

d

(idk if its right but i think it is)

pts with the following criteria all qualify for…

1. pts with HR+ / HER2 - with high risk of relapse (based on additional testing)

2. HER2+

3. HR- and HER2- (triple negative)

chemotherapy

what does ddAC stand for

dose dense doxorubicin and cyclophosphamide

what does TC mean

docetaxel and cyclophosphamide

what does T mean

paclitaxel or docetaxel

adjuvant chemotherapy for HER2- BC:

what are the three options?

1. ddAC x 4 cycles then T q2w x 4 cycles

2. ddAC x 4 cycles then weekly T x 12 cycles

3. TC q21 days x 4 cycles

Which adjuvant chemo regimens for HER2- require growth factor support?

all but weekly T (paclitaxel)

anthracycline ADE

red urine and body fluids

mucositis

cardiac dysfunction (usually permanent)

heart failure (irreversible)

anthracyclines are CI in which pts

low LVEF

pts on anthracyclines require an ECHO every ____ while on tx

3 months