Pharm: anti-cancer pt 2

What are the BCR-ABL kinase inhibitors (a type of tyrosine kinase)

imatinib and ponatinib

What drug’s MOA is:

binds tytosine kinase and prevents ATP from binding and activating the kinase

imatinib and ponatinib (the BCR-ABL kinase inhibs)

What drug can we use to treat CML Ph+, ALL Ph+, and CML when the kinase domain has the T315I ABL1 residue?

ponatinib

What drug so we use to treat ALL Ph+, and CML Ph+ as long as it doesn’t have the T315I in ABL1 residue

imatinib (ponatinib is the only one that is effective against the T315I mutation)

What drug’s AE include class effects and periorbital edema and skin rashes?

imatinib

What is the EGFR inhibitor?

cetuximab

What is the VEGF inhibitor?

bevacizumab

What drug’s MOA is that it is a competitive inhibitor of EGFR which: inhibits cell growth, induces apoptosis, decreases metrix metalloproteinase, and decreases VEGF

it also induced antibody dependent cellular cytotoxicity (where the NK cells fuck shit up)

cetuximab

What drug’s MOA is:

binds and neutralizes VEGF-A and prevents it from binding to the VEGF receptors: this prevents vascular permability and the formation of new blood vessels

bevacizumab

What drug is used to treat colorectal cancer that is KRAS wild-type / colorectal cancer KRAS

cetuximab and bevacixumab can treat colorectal cancer KRAS wild type (don’t have the KRAS gene)

they cannot treat the KRAS oncogene

cetuximab is ineffective against tumors with what mutation?

KRAS

What are the monoclonal antibodies that are used fro the treatment of HER-2-positive breast cancer?

trastuzumab and pertuzumab

What are the 4 drugs that we can use to treat HER-2-positive breat cancer

trastuzumab, pertuzumab, ado-trastuzumab emtansine, and lapatinib

What drug’s MOA:

binds to HER2 domain IV: prevents ligand-independent dimerization and induces receptor MAb internalization and degradation, and induces ADCC

trastuzumab

What drug’s MOA:

binds HER2 domain II: inhibits ligand-depepndent heterodimerization with other HERs and induces ADCC

pertuzumab

What drug’s MOA:

inhibits HER2 signaling and delivers the DM1 in the cancer cells and inhibits microtubule assembly and results in cell cycle arrest and apoptosis

ado-trastuzumab emtansine

What is the combo therapy for the tx of HER2-positive tumors?

taxane ± doxorubicin, cyclophasphamide, trastuzumab ± pertuzumab

What drug’s AE include cardiac failure, infusion reactions, pulmonary toxicity, and embryo-fetal death in pregnancy?

trastuzumab and pertuzumab

What drug’s MOA:

reversibly binds EGFR and HER2 and blocks the autophosphorylation of tyrosine residues and blocks the activation of second messengers Erk1/2 and Akt (intracellular)

lapatinib

mechanistically, how do trastuzumab and pertuzumab work together?

they target different domains on the HER2 receptor and together can do complete inactivation

Wha drug do we use for the treatment of hormone-receptor positive (usually estrogen) HER-2 negative breast cancer?

palbociclib

What drug’s MOA:

reversible inhibitor of CDK4 and CDK6 which prevents the progression from G1 to S cell cycle phase, leading to cell cycle arrest

palbociclib

Why is an aromatase inhibitor usually given with palbociclib?

An aromatase inhibitor is given with palbociclib to enhance the effectiveness of hormone therapy by lowering estrogen levels, which is crucial for the growth of hormone-receptor positive breast cancer.

What drug do we use for the oral treatment of BRCA-mutated advanced cancers?

olaparib

What drug’s MOA:

inhibits the PARP which inhibits the DNA strand break repair system

olaparib

What drug do we use to treat CD20-positive B cell malignancies?

rituximab

What drug’s MOA:

binds to the extracellular loop of CD20 and activated compleent-dependent B-cell cytotoxicity and mediates cell killing through antibody-dependent cellular toxicity

rituximab

What is a standard therapy for diffuse large B cell lymphoma?

R-CHOP: rituximab, cyclophosphamide, doxorubicin, and prednisone

rituximab also has function to treat ____ as well as B cell malignancies

certain autoimmune diseases such as rheumatoid arthritis.

When giving a pt rituximab, we should screen for what?

HBV, TB, Hep C, and HIV

What drug’s MOA:

binds cereblon (needed to tag proteins for degredation via ubiquitin-proteosome pathway)

also prevents the release of NFKB

lenalidomide

What are the 3 drugs we can use for multiple myeloma?

lenalidomide, bortezomib, and darutumumab

What drug’s AE include: SJS/TEN/DRESS, thromboembolic events, peripheral neuropathy, etc.?

lenalidomide

What drug is contraindicated in pregnancy and both males and females should use condoms if they are taking the drug due to it causing phocomelia?

lenalidomide

What drug’s MOA:

binds 20S core of 26S proteasome and inhibits it, inducing apoptosis and preventing the degredation of IKB which prevents the activation of NFKB

bortezomib

What drug’s MOA:

anti CD38: induces complement-dependent cytotoxicity, ADCC (NK cells), and apoptosis

daratumumab

What drug’s AE incude latent HBV infection and herpes zoster prophylaxis?

daratumumab

What drug decreases ingflammation, supresses neutrophil migration, and decreases the production of inflammatory mediators?

dexamethasone (a glucocorticoid)

What drug’s MOA:

blocks CTLA-4 and allows for enhaced T cell activation and proliferation

ipilimumab

What drug can we use to treat melanoma?

ipilimumab

What drug’s MOA:

PD-1 inhibitor that blocks the PD-1:PD-L1 interaction which prevents the ligand binding and leads to an immune response against the tumor

nivolumab

What drug’s MOA:

blocks PD-L1 and prevents the PD-ligand-mediated T cell suppression

atezolizumab

What drugs are associated with immune-related adverse effects like: ingflammarotry skin reactions, diarhea and colitis, heptotoxicityt, endocrinopathies, pneumonitis, autoimmune hemolytic anemia, and hemophagocytic lymphohistiocytosis

the immune checkpoint inhibitors: ipilimumab, nivolumab, and atezolizumab

What drug is a CAR-T cell therapy where the T cells are genetically engineered to direct the patient’s own cells against their own tumor cells

tisagenlecleucel

What drug targets CD19 (B cells)

tisagenlecleucel

What drug’s adverse effects include a cytokine release syndrome and immune effector cell neurotoxicity syndrome?

tisagenlecleucel