Therapeutics Exam 1 (Wendt and Dykhous) PT. 2 Flashcards
(200 cards)
1
Q
Uridine Analogs:
FdUMP mimics _____ and will bind to the active site of _________
A
mimics dUMP (hint the F is the fluorouracil that is screws everything up for DNA)
active site of: thymidylate synthase
2
Q
Uridine Analogs:
FdUMP will form a ternary complex with _____ and ______
A
enzyme (synthase) and reduced folate cofactor (aka the methyl donor!!)
3
Q
Uridine Analogs:
when FdUMP is in the ternary complex – the reaction cannot go to completion because why?
A
the F present (is usually an H) prevents the reaction to completing and letting the enzyme detach – enzyme is trapped!
4
Q
Uridine Analogs:
5-FU leads to _____ depletion and leads to the inhibition of DNA synthesis (via a “_______ death”)
A
TMP depletion
thymineless death
5
Q
Uridine Analogs:
5-FU is also converted to F-UTP and will affect _______
A
RNA processin and function
6
Q
5-FU resistance can occur by what 2 mechanisms?
A
downregulation of activating enzymes
upregulation of thymidylate synthase
7
Q
Thymidine and 5-FU drug interaction:
5-FU THEN thymidine = “_____” cytotoxic effect
Thymidine then 5-FU = “______” cytotoxic effect
A
then thymidine: is rescuing
thymidine 1st = enhances effect (giving this first will cause the cell to down regulate thymidine synthase!!)
8
Q
the drug _____ can be given with 5-FU and increase the efficacy by increasing the stability of the synthase complex
A
Leucovorate
9
Q
Leucovorate is a stable _____ cofactor and gets converted to _______ intracellularly
A
folate; tetrahydrofolate
10
Q
______ breaks down 5-FU (~5% of the population has a polymorphism and has a deficiency of this enzyme)
*deficiency of this enzyme can lead to a life threatening 5-FU
A
DPD (dihydropyrimidine dehydrogenase)
11
Q
who is FUdR (fluroreoxyuridine) different than 5-FU
A
FUdR is the deoxyribonucleoSIDE of 5-FU (aka FUdR has a sugar)
12
Q
Capecitabine is a orally active prodrug of _____
A
5-FU
13
Q
benefit of Capectiabine being a prodrug of 5-FU
A
longer 1/2 life!/can build up in tissues more
prodrug strategy generates higher levels of 5-FU selectively w/in some tumors
14
Q
Cytosine analogs:
primarily inhibit _______
A
DNA synthesis
15
Q
what bases are pyrimidines?
A
C & T
16
Q
what drugs are cytosine analogs?
A
Cytosine arabinoside…
Gemcitabine
17
Q
Cytosine arabinoside
is so structurally similar to deoxycytidine but the _______ makes it wack
A
B-OH at sugar 2’ (sugar is inverted somewhere)
18
Q
Cytosine arabinoside
gets converted to _____ intracellularly and then acts as a competitive inhibitor to _________
A
Ara-CTP
DNA polymerase alpha
(Ara-CTP will also get incorporated into DNA and make it wack)
19
Q
_________ will convert cytosine arabinoside to non-toxic uracil arbinoside
A
cytidine deaminase
20
Q
Cytosine arabinoside:
cytidine deaminase is low in the ______ therefore this drug is good to use for these types of cancer: ______ and ______
A
CNS!!!
meningeal leukemia and lymphoma (aka cancers in lining of brain and spinal cord)
21
Q
resistance mechanisms to cytosine arabinoside?
A
downregulation of deoxycytidine kinase (? - apparently an activating enzyme..)
upregulation of cytidine deaminase
downregulation of transport to move drug into cells
22
Q
Gemcitabine:
gets phosphorylated to ____ and ____ intracellularly
______ will inhibit ribonucleotide reductase (inhibits DNA synthesis)
___ gets incorporated in DNA and halts further chain elongation
A
dFdCDP; dFdCTP
dFdCDP
dFdCTP
23
Q
what drugs are used to stop purine biosynthesis
A
6-mercaptopurine
6-thioguanine
24
Q
what drugs are used to stop DNA and RNA incorporation of purine analogs
A
fludarabine
Nelarabine
Cladribine
25
6-Mercaptopurine: (6-MP)
| is a thio analog of _____
adenine
26
6-Mercaptopurine: (6-MP)
| will inhibit MULTIPLE enzymes in the de novo ________ pathyway
purine biosynthesis (aka blocks synthesis of purine nucleotides -- all of them not just Adenine)
27
6-Mercaptopurine: (6-MP)
| gets converted to _____ (the active metabolite) by _____
converted to: TIMP (thiosine monophosphate)
by: HGPRT
28
6-Mercaptopurine: (6-MP)
| is inactivated by ______
TPMT!!!
29
6-Mercaptopurine: (6-MP)
TPMT polymorphism occur in about ~10% of kids --- these can result in _____ toxicity
heterozygotes need about _____ of standard dose
homozygotes need about _____ of standard dose
hematologic;
65%
10%
30
6-Mercaptopurine: (6-MP)
| is also broken down by ________ (not just TPMT)
xanthine oxidase
31
what drug can increase the risk of 6-Mercaptopurine: (6-MP) toxicity
allopurinol (xanthine oxidase inhibitor)
32
6-Thioguanine: (6-TG)
| is very similar to 6-MP but the main difference is _________
allopurinol (canthine oxidase inihibitor) DOES NOT block breakdown of 6-TG
*6-TG and 6-MP both get activated by HGPRT and get inactivated by TPMT
33
Arabino adenosine analogs will interfere with _____ and _______ aka inhibit DNA replication and transcription
*what drugs are arabino adenosine analogs
interfere with DNA polymerase and ribnucleotide reductase
| fludarabine; Nelarabine; (Cladribine - has an extra MOA but still an adenosine analog..)
34
which Arabino adenosine analogs is used to treat blood cancers because phosphorylation keeps it in the bloodstream
fludarabine (it has sugar and phosphate!! - charge)
35
Cladribine will inhibit __________ and for some reason that enzyme is critical for ___ cells
inhibit adenosine deaminase (converts adenosine to inosine...?)
critical for B cells! -- aka useful for leukemias
36
Folate is vitamin B___
9
37
Folate enters "folate pool" as ______ which is (active or inactive)
FH2 (dihydrofolate) --- inactive
38
Dihydroflate (FH2) gets converted to tetrahydrofolate by ______
DHFR (dihyrdofolate reductase)
39
Folate Cycle:
inhibit _____ will reduce FH4 pools and folate pools accumulate as the inactive dihydrofolate ----->
____ and _____ synthesis decreases
DHFR;
TMP and purine nucleotide synthesis decreases!!
40
What compounds will bind and inhibit DHFR
Methotrexate
Pralatrexate
Pemetrexed
(they all similar structures to folic acid)
41
resistance to MTX (methotrexate) can happen how?
DHFR gene is amplified or mutation in DHFR gene leads to resistance
decrease polyglutamylation = decreased intracellular MTX accumulation
42
MTX can have increased accumulation in cells if ______ occurs
polyglutamylation
43
what is the "extra benefit" of pralatrexate
*compared to MTX just inhibiting DHFR
it is designed to accumulate in tumor cells --- selectively enters tumor cells that are expressing RFC-1 (reduced folate carrier type)
RFC-1 is typically overexpressed on tumor cells over normal cells
44
what is the "extra benefit" of Pemetrexed
*compared to MTX just inhibiting DHFR
also inhibits thymidylate synthase
| glycinamide ribonucloetide formyltransferase
aka less susceptible to drug resistance
45
how is Leucovorin used when in conjuction with MTX?
used to rescue normal tissues bc it is a stable folate cofactor
46
hydroxyurea MOA?
decreases production of deoxyribonucleotides BY inhibiting ribonucleotide reductase
47
hydroxyurea MOA?
| DNA synthesis is inhibited in the ___ Phase
S
48
MOA of Actinomycin?
binds DNA and inhibits transcription by RNA polymerase
| Aromatic drugs --- slips into DNA and intercolates stuff
49
MOA of Actinomycin?
| DNA synthesis is inhibited in the ___ Phase
any phase! non cell cycle specific (unlike other antimetabolites)
50
most antimetabolites affect the _____ phase in the cell cycle
S
51
Topoisomerases provide a mechanism to reduce ______ and provide access to _________
reduce: localized supercoiling
access: to double stranded DNA
52
Topoisomerase I:
| will cut ______ DNA and relax the remaining strand and ______
cut ONE strand of double stranded DNA;
| and reanneal
53
Topoisomerase I inhibitors:
| mechanism?
the inhibitor has a strong nucleophile spot -- will bind to topo I when it is attached to DNA
prevents Topo I from religating the cut DNA
54
most cells in ____ phase are sensitive to Topo I inhibitors
S
55
most topoisomeraise inhibitors will have a polycyclic _____ motif for intercalation --- these will preferentially stack with _____
aromatic; guanine
56
Drug resistance possibilities with Topo I inhibitors
PGP overexpression
MRP overexpression (multidrug resistant protein)
GLUTATHIONE S-TRANSFERASE overexpression\
Topo downregulation or mutation to inhibit binding
57
what drugs are Topo I inhibitors
topotecan
irontecan
(the camptothecins)
58
Topo I inhibitors:
Camptothecin - natural product: low solubility/unpredictable toxicity
Topotecan: water soluble analog of camptothecin
Irinotecan: is a prodrug made into _____
Sn-38 *** related to genetic testing!!!
59
why do genes affected irinotecan?
active metab of irinotecan = SN-38;
SN38 is metabolized by UGT1A1
toxicity of irinotecan can happen if low expression of UGT1A1
60
Topo II is able to relieve ______ and ______
torsional strain; untangle DNA
61
two forms of Topo II:
Top2A and Top2B: which is most targeted? and why?
Top2A:
| is required for decatenation of cells during mitosis
62
Anthracyclines: inhibit ______
Topo II
63
what drugs are Anthracyclines:
Doxorubicin
Dauomycin
Epirubicin
Idarubicin
64
how do Anthracyclines work?
multiple mechanisms:
intercalator
FREE RADICAL causes DNA damage
Inhibit Topo II***
65
issue with Anthracyclines?
free radical damage --> cardiotoxicity
66
Topo II inhibitors - Anthracyclines:
| which one is most widely used?
doxorubicin
67
Topo II inhibitors - Anthracyclines:
| which one has a dark red color/known as red death/red devil
doxorubicin
68
Topo II inhibitors - Anthracyclines:
| which one has less cardiotoxicity than doxorubicin and faster elimination
epirubicin
69
Topo II inhibitors - Anthracyclines:
| which one has increased fat solubility and cellular uptake
Idarubicin
70
which drug can be given with anthracyclines to decrease cardiotoxicity and how does it work
Dexrazoxane;
binds to iron/blocks iron-oxygen toxicities;
cardiotoxicity of doxorubicin and daunomycin believed to be caused by iron catalyzed free radical formation!!!
71
Mitoxantrone works how?
similar to anthracyclines but NOT an anthracycline --- will intercalate and inhibit topo II buuut NO FREE RADICAL TOXICITY = less cardiotoxicity!!!!!
72
how do Topo II inhibitors - Epipodophyllotoxins work?
inhibit religation of double stranded breaks induced by Topo II but DO NOT INTERCALATE
73
what drugs are Topo II inhibitors - Epipodophyllotoxins
Etoposide and Teniposide
74
what cell phase are they effective?
Anthracyclines:
Epipodophyllotoxins:
Anthra: non cell cycle specific
Epipop: G2 block
75
drug resistance problems with Topo II inhibitors?
PGP overexpression
MRP overexpression (multidrug resistant protein)
GLUTATHIONE S-TRANSFERASE overexpression - ONLY anthracyclines
increased DNA damage repair
Topo II downregulation or mutation to inhibit binding
76
how does bleomycin work?
has charged side chain and will intercalate with DNA and then imidazole part does Fe+/O2 species generate DNA free radical
radical leads to DNA single strand/double strand breaks
77
bleomycin:
______ is dose limiting and cumulative
and myleosuppression is minimal!!
pulmonary toxicity
78
bleomycin:
| gets inactivated by _________ which is in high concentrations for everywhere but _______
by aminohydrolase
skin and lungs (why pulmonary toxicity and rash ADEs)
*resistant cancers will have elevated aminohydrolase
79
what are the two major general microtubule inhibitor drug classes
Microtubule destabilizer
and
microtubule stabilizer
80
microtubule stabilizers will make microtubules "_____"
and
microtubule destabilizers will _______
stabilzers "frozen"
destabilizers "won't form"
81
Vinca alkaloids prevent _______
| microtubule assembly or microtubule disassembly
microtubule assembly
82
Taxanes prevent _____
| microtubule assembly or microtubule disassembly
disassembly
83
Vinca alkaloids- microtubule inhibitors:
bind to _____ and leads to inhibition of microtubule _______
ADE is ________
tubulin; ASSEMBLY;
peripheral neuropathy (b/c microtubules are critical to nerve cell axon function)
84
Vinca alkaloids- microtubule inhibitors:
| are (small or large) molecules
large
85
Vinca alkaloids- microtubule inhibitors:
| main drug resistance issue?
PgP transporter
86
microtubule inhibitors work in the _____ cell cycle phase
M (because duh thats when the chromosomes separate and need microtubules)
87
Spindle Assembly Checkpoint:
_______ need to be attached to spindle microtubules;
there needs to be _______
kinetochores
kinetochore tension
88
what drugs are vinca alkaloids
vincristine
vinblastine
vinorelbine
(neurotoxicity and myleosuppression is prevalent with these)
89
what does Erubulin do?
prevents elongation of microtubules!! so prevents microtubule assembly (sorta)
and has LOW RATE OF NEUROTOXICITY compared to the the vinca alkaloids
90
what drugs are taxanes
paclitaxel
docetaxel
cabazitaxel
91
how do taxane drugs work?
promote microtubule assembly into STABLE bundles (leads to less free tubulin and prevent microtubule formation at spindle -- since stable the microtubules do not depolymerize --> mitotic arrest/sister chromatids cannot separate)
92
Taxane drugs:
| drug resistance problem?
great substrates for PGP transporter (except Cabazitaxel!!)
| and tubulin mutations
93
what are epothilones
Ixabepilone
| similar action to taxanes but more potent and are poor PGP substrates
94
taxanes:
| ADE?
neurotoxicity
95
Misc Agents:
| Aflibercept MOA?
fusion protein: VEGF parts and Fc portion of IgG
96
Types of posttranslational modification?
phosphorylation and acetylation and methylation...
97
Misc Agents:
| Romidepsin MOA?
inhibits HDAC
98
if a histone is acetylated that means the gene will or will not have transcriptional activity
will have
99
if a histone is deacetylated --- that promotes _______ and prevents ________
promotes heterochromatin
| prevents transcription
issue when tumor suppressor genes are deacetylated and then not being transcribed
100
ADE of Romidepsin
activation of infections (parts of DNA that we don't normally use can have come from viruses ---- evolution stuff --- and then now they are activated)
101
Misc Agents:
| Vorinostat MOA?
HDAC inhibitor
102
Misc Agents:
| Belinostat MOA?
HDAC inhibitor
103
methylation usually happens in the _____ area of genes and will turn the gene (on or off)
methylation happens because of the _____ enzyme
promoter; off
DNMT (DNA methylation transferase)
104
Misc Agents:
| Azacytidine MOA?
DNMT inhibitor
105
Misc Agents:
| decitabine mOA?
DNMT inhibitor
106
why would trentinoin be used?
retinoids promote differentiation and inhibit proliferation
107
Retinoids:
| _____ converts ______ into a transcriptional activator and induces differentiation of leukemic cells
ATRA (all trans retinoic acid receptor); PML-RAR (promyeloctyic leukemia - retinoic acid receptors)
108
APL (acute promyelocytic leukemia) is characteried by the fusion of what two things?
RAR and PML
| promyeloctyic leukemia - retinoic acid receptors
109
Misc Agents:
| Bexarotene MOA?
3rd gen retinoid that acts as agonist for RXR (rentinoids receptors)
110
RXRs tend to form heterodimers with what types of receptors?? and then go act as transcription factors that increase cellular differentiation/inhibit proliferation and induce apoptosis!!
RARs or vit. d receptor or thyroid receptor, or PPAR
111
Misc Agents:
| MOA of tazemetostat?
inhibits methyltransferase activity of EZH2
112
EZH2 will do the the trimethylation of lysine 27 of H3 histones.... aka will lead to the ________ of ______ genes
repression; tumor suppressor
113
Misc Agents:
Thalidomide:
strong anti-_____ activity - wil block effects of ____ and ____
anti-angiogenic activity!
| blocks VEGF!!! and bFGF
114
Misc Agents:
Thalidomide and its analog _______
is a potent ______ aka why it has a REMS program
Pomalidomide or Lenalidomide
| teratogen --- must prevent pregnancy
115
what drugs are proteosome inhibitors
bortezomib, carfilzomib, and ixazomib
| the -zomibs!!!
116
what are proteosome inhibitors helpful?
so proteosomes break down misfolded proteins...
normally a molecule called Ik-Ba will get phosphorylated and then ubiquinated --- once that happens Nf-kB can go to the nucleus and drive transcription of pro-inflammatory and proliferation genes...
long story short if the Ik-Ba cannot get degraded then Nf-Kb cant get to the nucleus
(then hella misfolded protein in cell leads to apoptosis)
117
Misc Agents:
| what drugs are used for basal cell carcinoma
Vismodegib
and
sonidegib
they will bind to and inhibit smoothened from activating GLI1
(hedgehog signaling??)
118
Components of Hedgehog signaling:
| Hedgehog binds to ______ and release the inhibition on ______ this leads to nuclear translocation of ______
binds to patched; smoothened; GLI1
119
how do vismodegib and sonidegib work?
they will bind to and inhibit smoothened from activating GLI1
120
_____ overexpression allows cancer cells to evade apoptosis by sequestering pro-apoptotic proteins
BCL-2
121
what drug selectively binds to BCL-2 which leads to apoptosis
venclexta/venetoclax
122
how does venclexta work?
BCL-2 inhibitor
selectively binds to BCL-2 --> will free pro-apoptotic proteins --> lead to apoptosis
123
what kind of molecule is venclexta the first of?
small molecule that inhibits a protein-protein interaction
124
Misc Agents:
| MOA of Omacetaxine?
inhibitor of protein translation/inhibits elongation step of protein synthesis
125
why is the drug asparaginase useful in cancer cells?
normal cells make asparagine with the asparagine synthase enzyme....
malignant cells do not have this enzyme:
if you use this drug (it decrease asparagine levels)
normal cells can adapt and increase the synthase enzyme
cancer cells cant adjust and dieeee
126
Bone metastasis:
| bisphosphonates good why?
bisphosphonates stop osteoclasts/stop breakdown of bone
when bone is broken down the remnants will actually feed tumor cells --- booooo
127
Misc Agents:
| Denosumab?
inhibitor of RANKL!
RANKL binds to RANK on osteoclasts and lead to the bone resorption process
128
_______ is a natural binder of RANKL
OPG (osteoprotegerin)
129
explain TLS
TLS = tumor lysis syndrome
| aka massive raise in uric acid in the blood because of high DNA content being released
130
TLS leads to renal issues how?
uric acid can precipitate in renal tubules ---- worse kidney function = worsening hyperkalemia and hyperphosphatemia and Ca2+ and this all precipiates in the kidneys too
(the hyperkalemia leads to cardiac rhythms and arrhythmias)
131
what drugs can be given for helping with TLS
Allopurinol (duh uric acid is a problem in TLS) - use prophylactically
Rasburicase - a recombinant urate oxidase --- breaks down uric acid (humans do not express this endogenously)
132
Tisagenlecleucel:
| MOA?
aka Kymriah
t cells are isolated from patient ---- they are grown with CAR stably expressed;
then cells grown are put back in patient
aka pt essentially gets immunized against CD-19 and
133
Kymriah leads to all ______ cells being eliminated
immature B cells
134
Provenge (Sipuleucel) is approved for _______ cancer
metastatic prostate
135
Provenge (Sipuleucel) --- how does it work
they stimulate pts own immune system to attack the cancer
take APCs from pt --- give the APCs the "drug" (PAP-GM-CSF) -- PAP = a phosphotase and GM-CSF macrophage colony stimulating factor
136
the ____ virus is associated with liver cancer
HBV (hepatitis B) virus
137
why is it hard to vaccinate against tumor proteins??
well tumors come from us..therefore it is hard to target self proteins
138
HPV cancer happens because HPV is a _____ virus that produces proteins (___ and ___) that will increase proliferation and allow for accumulation of DNA mutations
E6 and E7
139
which HPV types are the major causative agents for cervical cancer and therefore can be vaccinated against as means to prevent HPV infection
HPV 16 and 18
140
HPV vaccines can help prevent against what kinds of cancer?
most notably cervical (but also vulvular, vaginal, anal, and penile cancers)
141
Gardaisl vs Ceravarix:
| which one is quadrivalent
gardasil (has 16, 18, and types 11 and 6 covered)
142
Gardaisl vs Ceravarix:
| which one is bivalent
ceravarix (just 16 and 18 HPV types)
143
MOA of Aldesleukin?
it is a recombinant protein of Interleukin 2 and will activate T cells
(very pro-inflammatory cytokine - enhances lymphocyte mitogenesis and cytotoxicity)
VERY non specific!!
144
MOA of Interferon Alpha:
recombinant protein -- but has direct antiproliferative effect
and enhanced host immune response
145
ADE Comparisons:
Anthracyclines causes cardiotoxicity ----
rank order of toxicity issues of daunorubicin, doxorubicin, and epirubicin (lowest to highest cardiotoxicity)
epirub --> doxo --> danu
*danu is the worst one
146
ADE Comparisons:
| Mitxoantrone or Doxorubicin has worst cardiotoxicity?
doxorubicin:
| mitoxantrone does not have free radical formation -- has less cardiotox
147
most microtubule drugs are critical to _____ function (as well as normal cell function) and lead to ________
nerve cell axon; peripheral neuropathy
148
Vince Alkaloid ADE Comparisons:
Vincristine, Vinblastine, or Vinorelbine?
which one has really bad neurotoxicity
vincristine
149
Vince Alkaloid ADE Comparisons:
Vincristine, Vinblastine, or Vinorelbine?
which one has dose limiting myleosuppression
vinblastine and vinorelbine
150
Vince Alkaloid ADE Comparisons:
Vincristine, Vinblastine, or Vinorelbine?
which one can cause severeeee local inflammation because of extravasation
vincristine
151
ADE Comparisons:
| Erubulin or Vincristine has neurotoxicity worse?
vincristine
erubilin - low rate of neurotoxicity for a microtubule
152
ADE Comparisons:
| Taxanes get pumped out the cell ----except one does not -- which one?
Cabazitaxel`
153
ADE Comparisons:
| cyclophosphamide or ifosphamide has increased CNS toxicity
ifosphamide
154
ADE Comparisons:
Cisplatin, Carboplatin, or Oxaplatin?
has dose limiting neprhotoxicity
cisplatin
155
ADE Comparisons:
Cisplatin, Carboplatin, or Oxaplatin?
has dose nephrotoxicity but low bone marrow toxicity
cisplatin
156
ADE Comparisons:
Cisplatin, Carboplatin, or Oxaplatin?
has minimal nephrotoxicity
both carboplatin and oxaplatin
157
ADE Comparisons:
Cisplatin, Carboplatin, or Oxaplatin?
has significant bone marrow toxicity
carboplatin
158
ADE Comparisons:
Cisplatin, Carboplatin, or Oxaplatin?
has acute and chronic neuropathy
oxaplatin
159
Indications for Drugs:
| the hedgehog signaling drugs (Vismodegib and Sonidegib)
basal cell carcinoma
160
Indications for Drugs:
| Tamoxifen
ER+ or PR+ breast cancer
(ok for prevention of breast cancer!!)
(also ok in pre or post menopausal women)
161
Indications for Drugs:
| Fulvestrant
ER+ breast cancer -- POST menopausal women
162
ADE Comparisons:
| Aromotase inhibitors or SERMs hae increased risk for fractures
aromatase inhibitors because decrease estrogen in general (SERMs are agonists at the bones!! aka yay healthy bones)
163
Indications for Drugs:
| medroxyprogesterone
prevent endometrial cancer (post menopausal women!)
can be used in appetite stimulation/wt gain and antiemetic
164
Indications for Drugs:
| LHRH analogs
for women: premenopausal breast cancer (estrogen dependent..)
for men: prostate cancer
165
Indications for Drugs:
| abarelix
prostate cancer (LHRH antagonist)
166
Indications for Drugs:
| degarelix
prostate cancer (LHRH antagonist)
167
Indications for Drugs:
| exemestane
ER+ breast cancer in POST menopausal women
168
Indications for Drugs:
| Gefitinib
NSCLC -- have mutations on exon 19 or 21 (L858R mutation!)
169
Indications for Drugs:
| Erlotinib
NSCLC -- have mutations on exon 19 or 21 (L858R mutation!)
170
Indications for Drugs:
| Afatinib
NSCLC (covalent) and does L858R mutation (NOT T790M :( )
171
Indications for Drugs:
| Osimertinib
NSCLC that has T790M mutation!!!
172
Indications for Drugs:
| Lapatnib
tx HER2+ breast cancer
| usually used if pts progressed when on trastuzumab therapy
173
Indications for Drugs:
| Nerabitinib
tx HER2+ breast cancer
| usually used if pts progressed when on trastuzumab therapy
174
Indications for Drugs:
| Cabozantinib
it is a cMET inhibitor --- cMET is amplified in some lung cancers
ALSO thyroid cancer!!
will target RET and VEGFR too
(good when ROS1 mutations have occurred with crizotinib)
175
Indications for Drugs:
| Crizotinib
it is a cMET inhibitor --- cMET is amplified in some lung cancers
also a EML4-ALK inhibitor: 6% of NSCLC pts have this fusion gene (needs diagnostic for the fusion gene)
176
BCR-Abl is seen in about 95% of what kinds of cancer?
the Philadelphia chromosome (BCR-Abl) is found in CMLs!! (chronic myelocytic leukmeia)
177
Indications for Drugs:
| imatinib
the first kinase ever!
is indicated for CML (for the BCr-Abl fusion gene)
but also indicated for GIST because it targets c-kit as well!
178
Indications for Drugs:
| nilotinib
for CML (the BCR-Abl fusion gene) good for when there are mutations that imatinib cant take care of`
179
Indications for Drugs:
| Ponatinib
CML!
it is effective against all major mutant forms of the BCR-Abl fusion gene!
will inhibit the T3151 mutation! (aka the gatekeeper mutation?)
180
Indications for Drugs:
| Dasatinib
```
for CML (the BCR-Abl fusion gene)
does NOT do the T3151 mutation though
```
181
Indications for Drugs:
| Bosutinib
```
for CML (the BCR-Abl fusion gene)
does NOT do the T3151 mutation though
```
182
Indications for Drugs:
| Alectinib
for EML4-ALK fusion gene in NSCLC (will need genetic testing!!)
183
Indications for Drugs:
| Sorafenib
NOT melanoma because cant do the V600M mutation
can be used for renal carcinoma and hepatocellular carcinoma
184
Indications for Drugs:
| Vemurafenib
melanoma! can inhibit BRAF when V600 mutation is there
careful because can activate the wild type and lead to tumor growth :(
185
Indications for Drugs:Dabrafenib
melanoma with V600 mutation!!!
| careful because can activate the wild type and lead to tumor growth :(
186
Indications for Drugs:
| Trametinib
it is a MEK inhibitor: MEK is downstream from BRAF --- therefore melanoma?
do NOT use if pt has previous BRAF therapy
187
Indications for Drugs:
| Cobimetinib
it is a MEK inhibitor: MEK is downstream from BRAF --- therefore melanoma?
do NOT use if pt has wild type BRAF
188
what kinase inhibitors are TYPE III
the MEK inhibitors
| tramitenib and combimetinib
189
what drug is notably a TYPE II kinase inhibitor
imatinib
190
Indications for Drugs:
| Idelalisib
P13K inhibitor is for CLL (chronic lymphocytic leukemia)
191
Indications for Drugs:
| Ibrutnib
b cell leukemia
| it is targeting BTK which is downstream from b cell receptors
192
Indications for Drugs:
| Acalabrutinib
b cell leukemia
| it is targeting BTK which is downstream from b cell receptors
193
Indications for Drugs:
| Vandetanib
thyroid cancer!!
has multiple cancers (like cabozitinib)
targets VEGFR and RET, and EGFR
194
Indications for Drugs:
| Temsirolimus
renal cell carcinoma!
| mTOR inhibitors/rapalogs are good renal cell carcinoma
195
Indications for Drugs:
| Everolimus
renal cell carcinoma
196
Indications for Drugs:
| the CDK inhibitors (-ciclibs)?
ER+ but HER- breast cancer --- usually in combo with an anti-endocrine drug
197
Indications for Drugs:
| Trastuzumab
breast cancer that over expresses HER2
198
Indications for Drugs:
| Pertuzumab
breast cancer that over expresses HER2
199
Indications for Drugs:
| Cetuximab
colorectal, head and neck cancers (even though it targets EGFR... it is not for NSCLC because the lung cancer will have mutations)
200
Indications for Drugs:
| Panitumumab
colorectal cancer
| need to check for KRAS mutational status
