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Pharm-Cancer Unit 1 > Molecular Targeted Therapy > Flashcards

Molecular Targeted Therapy Flashcards

1
Q

Imatinib MOA

A

binds to Bcr-Abl at ATP binding site, blocking its tyrosine kinase activity; Bcr-Abl fusion protein created by t(9;22)

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2
Q

Imatinib TU

A

first-line therapy for CML; also approved for unresectable and metastatic GI stromal tumors (most common mesenchymal tumor of GI tract; KIT and PDGFRA mutations)

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3
Q

Imatinib Toxicity

A

minimal - nausea, vomiting, myalgia, arthralgia, myelosuppression

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4
Q

Imatinib Intrinsic Resistance

A

mutations in Bcr-Abl making it insensitive; enhanced binding to proteins in circulation and/or drug efflux

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5
Q

Imatinib relapse after initial response

A
  1. mutations in Abl kinase making it less sensitive
  2. Bcr-Abl amplification
  3. persistent inhibition of Bcr-Abl; other molecular abnormalities take over
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6
Q

Second Generation TKIs

A

nilotinib and dasatinib

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7
Q

all trans-retinoic acid (RA) MOA

A

induces terminal differentiation of malignant promyelocytes in APL; PML-RAR(alpha) fusion protein from t(15;17) cannot induce normal differentiation at physiological RA conc.and possibly acts as an oncoprotein

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8
Q

all trans-RA TU

A

APL (acute promyelocytic leukemia)

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9
Q

all trans-RA Tox

A

if used alone, 1/3 pts develop ‘leukocyte activation syndrome’ = inc white count; fever, resp distress, weight gain, pleural or pericardial effusion, occasional renal failure
***can avoid this by giving corticosteroids with RA Tx
other side effects = skin and lip dryness, nausea, headache, arthralgias, bone pain

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10
Q

all-trans RA resistance

A

induction of cytochrome P450 to enhance RA catabolism; alterations in level of cytosolic RA binding protein II (CRBP II) that could affect RA transport to target

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11
Q

trastuzumab (herceptin) MOA

A

humanized mAb against HER2 (Erb-B2) growth factor receptor; prevents transduction of proliferation and survival signals

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12
Q

trastuzumab TU

A

HER2 positive breast cancer; works best in combination with paclitaxel or doxorubicin

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13
Q

trastuzumab Tox

A

hypersensitivity reaction
cardiotoxicity (ventricular dysfunction and CHF)
can enhance cardiotoxic effects of doxorubicin

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14
Q

cetuximab (erbitux) MOA

A

competes with ligands for binding to EGFR and inhibits its TK activity, blocking growth promoting and survival signals

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15
Q

cetuximab TU

A

colorectal (w/ irinotecan or FOLFIRI), squamous cell carcinoma of head and neck; works best in combination with cisplatin or other chemo drugs
FOLFIRI = leucovorin, 5-FU, irinotecan

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16
Q

rituximab MOA

A

binds to CD20 antigen (which is present on all B cells); eliminates CD20 positive follicular lymphoma by: direct activation of apoptosis, complement activation, cell-mediated cytotoxicity

17
Q

rituximab TU

A

non-Hodgkins lymphoma (particularly follicular lymphomas - relapsed or refractory)

18
Q

cetuximab Tox

A

allergic rxn, cardiac events, skin problems, renal failure, PE, hypomagnesemia, hypocalcemia, hypokalemia

19
Q

rituximab Tox

A

hypotension, flushing, fever and chills, asthenia, nausea, hypersensitivity rxn

20
Q

vemurafenib MOA

A

BRAF inhibitor; blocks its constitutive activity to decrease cell proliferation and survival

21
Q

vemurafenib TU

A

BRAF mutation positive metastatic melanoma; BRAF is a serine threonine kinase downstream of RAS and RTKs, most commonly mutated at V600 in cutaneous melanomas not associated with sun damage

22
Q

vemurafenib Tox

A

arthralgia, fatigue, photosensitivity, alopecia, nausea, diarrhea
cutaneous squamous cell carcinoma, keratoacanthoma
QT prolongation, enhancing risk of ventricular arrhythmias
new primary cutaneous melanoma

23
Q

vemurafenib contraindications

A

wt BRAF melanomas, electrolyte abnormalities, long QT syndrome, pts on durgs that will cause QT prolongation

24
Q

dabrafenib MOA and TU

A

BRAF inhibitor for BRAF mutation positive metastatic melanoma

25
Q

dabrafenib Tox

A

cutaneous squamous cell carcinoma, keratoacanthoma, melanoma
serious febrile drug rxn
uveitis, iritis
hyperglycemia
hyperkeratosis, headache, pyrexia, arthralgia, papilloma, alopecia, palmar-plantar erythrodyesthesia, rash, back pain, cough, constipation, myalgia, nasopharyngitis
may inhibit fertility in men

26
Q

trametinib MOA and TU

A

inhibits MEK (extracellular signal-related kinase) in BRAF mutation positive metastatic melanoma

27
Q

trametinib Tox

A 
cardiomyopathy
retinal pigment epithelial detachment
retinal vein occlusion
interstitial lung disease
serious skin toxicity
normal side effects
may inhibit fertility in females
28
Q

ipilimumab (yervoy)

A

CTLA-4 inhibitor, expected to stimulate immune system; approved for melanoma

29
Q

IL-2

A

modulate immune system; used to treat melanoma

Pharm-Cancer Unit 1 (9 decks)

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