Final Exam Flashcards
(193 cards)
1
Q
What are the hallmarks of cancer?
A
-sustaining proliferative staging
-avoiding immune destruction
-enabling replicative immortality
-activating invasion and metastasis
-inducing or accessing vasculature
-genome instability and mutation
-resisting cell death
2
Q
What are the characteristics of cancer?
A
-uncontrolled cellular growth
-invasion of tissue
-metastasis
3
Q
neoplasm
A
a new growth; may be benign or malignant
4
Q
tumor
A
a lump or swelling; may be benign or malignant
5
Q
cancer
A
any malignant neoplasm
6
Q
hyperplasia
A
an increase in organ or tissue size due to an increase in the number of cells; can be physiologic, compensatory, or pathologic
7
Q
metaplasia
A
an adaptive substitution of one type of adult tissue to another type of adult tissue
8
Q
dysplasia
A
an abnormal cellular proliferation in which loss of normal architecture occurs
9
Q
anaplasia
A
a loss of structural differentiation
10
Q
carcinoma
A
malignant neoplasm of squamous epithelial cell origin
11
Q
adenocarcinoma
A
malignant neoplasm derived from glandular tissue
12
Q
sarcoma
A
malignant neoplasm with origin in mesenchymal tissues or its derivatives
13
Q
lymphoma and leukemia
A
malignant neoplasms of hematopoietic tissues
14
Q
melanoma
A
a type of cancer of pigment-producing cells (melanocytes) in the skin or eye (uveal melanoma)
15
Q
blastoma
A
malignancies in precursor cells
16
Q
teratoma
A
a germ cell neoplasm made of several different differentiated cell/tissue types
17
Q
Is p53 an oncogene or tumor suppressor?
A
tumor suppressor
18
Q
Is p16 an oncogene or tumor suppressor?
A
tumor suppressor
19
Q
Is Ras an oncogene or tumor suppressor?
A
oncogene
20
Q
Is Rbl an oncogene or tumor suppressor?
A
tumor suppressor
21
Q
What is a limitation of phase-specific drugs?
A
number of cells in specific phase at that time
22
Q
What are dose-limiting toxicities of chemotherapy?
A
-infections
-hemostasis
-anemia
-GI side effects
-N/V
-loss of appetite
23
Q
What are mechanisms of drug resistance for chemotherapy?
A
-altered drug metabolism
-changes in drug target or function
-physiological changes
-cell survival mechanisms
24
Q
How can drug metabolism be altered?
A
-increased transport of drugs out of cell through efflux pumps
-reduced transport into cell
-decreased activation of prodrug
-increased detoxification of drug molecule
25
How can drug target or function be changed?
-increased expression of drug target through gene amplification or expression
-emergence of structurally mutated target
-rewire pathway to bypass need for drug target
26
What are physiological changes that can lead to drug resistance for chemotherapy?
-refuge of cancer cells in drug-protected anatomical sites
-massive stromalization
-changes in cell state
27
What are cell survival mechanisms?
-activation of anti-apoptotic regulators
-increased repair of damage caused by chemotherapies
28
What is the suffix of androgen receptor antagonists?
-lutamide
29
What are the mechanisms of action of androgen receptor antagonists?
-prevent androgen receptor translocation to nucleus
-inhibits androgen receptor binding to DNA
30
What is the indication of androgen receptor antagonists?
metastatic and non-metastatic prostate cancer
31
What is the mechanism of action of abiraterone?
inhibits function of 17α-hydroylase and 17,20 lyase
32
What is the function of 17α-hydroylase and 17,20 lyase?
convert progestogens to androgens
33
What is a common side effect of abiraterone?
increased cholesterol
34
What type of drug is tamoxifen?
selective estrogen receptor modulator (SERM) prodrug
35
Does tamoxifen have agonist or antagonist activities?
agonist and antagonist
36
What are tamoxifen antagonist effects?
-blocks estrogen-dependent breast cancer cell proliferation
-hot flashes
37
What are tamoxifen agonist effects?
-increased incidence of endometrial cancer
-preservation of bone density in postmenopausal women
38
What population is tamoxifen effective in?
pre- and post-menopausal women
39
What are the indications for tamoxifen?
resected and metastatic ER+/PR+ breast cancer
40
What is the recommended duration of use for tamoxifen?
up to 5 years
41
What type of drug is fulvestrant?
selective estrogen receptor down-modulator (SERD)
42
Does fulvestrant have agonist or antagonist activities?
antagonist
43
What is the mechanism of action of fulvestrant?
binds to estrogen receptor and inhibits DNA binding --> rapid receptor degradation
44
What is the indication of fulvestrant?
ER+ metastatic breast cancer in postmenopausal women who have progressed on other anti-estrogen therapy
45
What is the route of administration of fulvestrant?
IM
46
What cancers do glucocorticoids have anti-cancer effects in?
-pediatric acute lymphoblastic leukemia
-multiple myeloma
-lymphoma
47
What are the most commonly used glucocorticoids in cancer treatment?
-methylprednisolone
-prednisolone
-dexamethasone
48
What is the suffix of non-steroidal aromatase inhibitors?
-trozole
49
Are non-steroidal aromatase inhibitors competitive or non-competitive?
competitive
50
What is the indication of non-steroidal aromatase inhibitors?
breast cancer in postmenopausal women
51
When should non-steroidal aromatase inhibitors be used in treatment?
first-line OR after 3-5 years of tamoxifen treatment
52
What is a side effect of non-steroidal aromatase inhibitors?
increased bone density loss
53
What are the two steroidal aromatase inhibitor drugs?
-exemestane
-androstenedione
54
What is the mechanism of action of exemestane?
-false substrate that aromatase converts to reactive intermediate
-intermediate binds irreversibly at active site and inactivates enzyme
55
What is the indication of exemestane?
ER+ breast cancer in postmenopausal women who have progressed on anti-estrogen therapy
56
What are side effects of exemestane?
-hot flashes
-occasional peripheral edema and weight gain
-increased cholesterol
57
What is the function of aromatase?
convert androgens to estrogens
58
What are two GnRH analogs?
-leuprolide
-goserelin
59
What are long-term side effects of GnRH analogs?
-hot flashes
-gynecomastia
-sexual dysfunction
60
What are the indications of GnRH analogs?
-premenopausal breast cancer
-palliative treatment of advanced prostate cancer
61
What is a clinical pearl of GnRH analogs?
temporary worsening of symptoms due to initial agonist effects
62
What drugs are given to premenopausal women with breast cancer?
-GnRH analogs
-tamoxifen
63
What drugs are given to postmenopausal women with breast cancer?
-tamoxifen
-aromatase inhibitors
-SERDs
64
What is the suffix of kinase inhibitors?
-nib
65
What is the mechanism of action of imatinib?
type II small molecule inhibitor of Abl tyrosine kinase
66
What is the mechanism of action of type II kinase inhibitors?
bind and stabilize inactive conformation of kinase
67
What is the indication of imatinib?
chronic myeloid leukemia (CML)
68
What are side effects of imatinib?
-N/V
-fluid retention and edema
-neutropenia and thrombocytopenia
69
What is the mechanism of action of ponatinib?
BCR-Abl inhibitor
70
What mutation can ponatinib inhibit that other BCR-Abl inhibitors cannot?
T315I
71
What is the mechanism of action of type I kinase inhibitors?
bind to active conformation of kinase
72
What type of FLT3 inhibitor is midostaurin?
first generation
73
Are first generation FLT3 inhibitors more broad or specific?
broad
74
What drugs are type I FLT3 inhibitors?
-midostaurin
-crenolanib
75
What is the indication of FLT3 inhibitors?
acute myeloid leukemia (AML)
76
What drug is a type II FLT3 inhibitor?
-quizartinib
77
What mutation are type II FLT3 inhibitors specific for?
internal tandem duplication (ITD)
78
What type of FLT3 inhibitor is crenolanib?
second generation
79
Are second generation FLT3 inhibitors more broad or specific?
specific
80
What is the suffix of rapamycin analogs?
-rolimus
81
What do rapamycin analogs inhibit the function of?
mTOR
82
What is the mechanism of action of rapamycin analogs?
inhibit immune response by blocking IL-2 signaling transduction
83
What is the indication of everolimus?
advanced renal carcinoma in patients who have failed sunitinib or sorafenib
84
Does everolimus inhibitor mTORC1 or mTORC2?
mTORC1
85
What is the mechanism of action of alectinib?
specific inhibitor of ALK
86
What does alectinib require before prescribing?
companion diagnostic test for fusion gene
87
What is the indication of alectinib?
ALK+ metastatic non-small cell lung cancer (NSCLC) with progression or intolerance to crizotinib
88
What is the mechanism of action of dabrafenib?
second generation BRAF-V600 inhibitor
89
What are the indications of dabrafenib?
-BRAF V600E/K-mutant metastatic melanoma
-BRAF-600+ NSCLC
90
What is the mechanism of action of trametinib?
inhibits kinase activity of MEK1 and MEK2
91
What type of kinase inhibitor is trametinib?
type III
92
What is the mechanism of action of type III kinase inhibitors?
occupy allosteric pocket outside ATP-binding pocket
93
What are side effects of trametinib?
-rash
-diarrhea
-lymphedema
94
What is the mechanism of action of acalabrutinib?
second generation covalent BTK inhibitor
95
What is the indication of acalabrutinib?
B-cell lymphoma
96
What are the EGFR inhibitor drugs?
-gefitinib
-afatinib
-osimertinib
97
What is the indication of gefitinib and afatinib?
metastatic NSCLC with EGFR exon 19 or 21 mutations
98
What are the side effects of gefitinib?
-fatigue
-rash
-diarrhea
99
What mutation is osimertinib effective against?
T790M
100
What is the mechanism of action of lapatinib?
reversible small molecule tyrosine kinase inhibitor blocking HER2 and EGFR signaling
101
What is the indication of lapatinib?
advanced metastatic cancer progressive on other therapies
102
What are side effects of lapatinib?
-diarrhea
-N/V
-reversible decrease in cardiac function
103
What is the mechanism of action of tucatinib?
small molecule tyrosine kinase inhibitor that preferentially binds HER2
104
What is the indication of tucatinib?
second-line treatment for advanced metastatic breast cancer progressive on other therapies
105
Which EGFR inhibitors bind covalently?
-afatinib
-osimertinib
106
What part of the cell cycle do antimetabolites target?
S phase
107
What is a dose-limiting toxicity of antimetabolites?
myelosuppression
108
What drugs are pyrimidine analogs?
-5-FU
-capecitabine
109
What are the mechanisms of action of 5-FU?
-conversion to FdUMP mimics dUMP --> TMP cannot be produced --> inhibition of DNA synthesis
-conversion to F-UTP --> fluorine interferes with RNA processing and function and with polyadenylation of mRNA
110
What drug is used as a rescue for 5-FU?
thymidine
111
What are resistance mechanisms of 5-FU?
-downregulation of activating enzymes that convert 5-FU to FdUMP
-upregulation of thymidylate synthaseW
112
What polymorphism increases susceptibility to 5-FU?
DPD
113
What drug is used synergistically with 5-FU?
leucovorin
114
What drugs are cytidine analogs?
-cytarabine (Ara-C)
-gemcitabine
115
What is the mechanism of action of cytarabine?
-converted to Ara-CTP intracellularly
-competitive inhibitor of DNA polymerase α
116
What cancer is cytarabine best at targeting?
meningeal leukemia and lymphoma
117
What are resistance mechanisms of cytarabine?
-downregulation of activating enzymes and transporter to move drug into cell
-upregulation of cytidine deaminase
118
What drug is used synergistically with cytarabine?
tetrahydrouridine
119
How is gemcitabine more beneficial than cytarabine?
higher potency
120
What drugs are purine analogs?
-6-mercaptopurine
-6-thioguanine
121
What is a resistance mechanism of 6-mercaptopurine?
loss of HGPRT
122
What polymorphism causes increased toxicity of 6-mercaptopurine?
TPMT
123
What is a drug interaction with 6-mercaptopurine but not 6-thioguanine?
allopurinol
124
What drug is an antifolate?
methotrexate
125
What is the mechanism of action of methotrexate?
DHFR inhibitor
126
What are resistance mechanisms of methotrexate?
-amplification of DHFR gene or mutation of DHFR to resistant form
-decreased polyglutamation
127
What is a side effect of methotrexate?
myelosuppression
128
What drug is used as a rescue for methotrexate?
leucovorin
129
What are side effects of alkylating agents?
-myelosuppression
-N/V
130
What drug class is chlorambucil in?
mechlorethamine derivatives
131
How are mechlorethamine derivatives more beneficial than mechlorethamine?
reduced reactivity and increased selectivity of nitrogen mustards
132
Are alkylating agents cell cycle phase specific?
No
133
What type of drug is cyclophosphamide?
prodrug alkylating agent
134
What are side effects of cyclophosphamide?
-bone marrow toxicity
-hemorrhagic cystitis
135
What drug is administered with cyclophosphamide to prevent hemorrhagic cystitis?
mesna
136
What type of drug is mitomycin C?
alkylating agent
137
What is a dose-limiting side effect of mitomycin C?
myelosuppression
138
What is the suffix of platinum drugs?
-platin
139
What is the mechanism of action of platinum drugs?
covalent crosslinkers
140
What type of crosslinks are formed by platinum drugs?
intrastrand
141
What type of tumors are platinum drugs highly effective for?
solid tumors
142
What are side effects of cisplatin?
-N/V
-bone marrow toxicity
-peripheral neuropathy
-ototoxicity
143
What is a dose-limiting side effect of cisplatin?
nephrotoxicity
144
What are resistance mechanisms of alkylating agents and platinum drugs?
-increased expression of DNA repair enzymes
-increased intracellular concentration of non-protein thiones
-increased expression of cellular glutathione S-transferase (GST)
145
What phase of the cell cycle are cells most susceptible to topoisomerase I inhibitors?
S phase
146
What are resistance mechanisms of topoisomerase I and II inhibitors?
-PGP overexpression
-MRP overexpression
-glutathione S-transferase overexpression
-topoisomerase downregulation or mutation
147
What is the suffix of camptothecins?
-otecan
148
What polymorphism causes increased toxicity of irinotecan?
UGT1A1
149
How many strands of DNA does topoisomerase I cut?
one
150
How many strands of DNA dose topoisomerase II cut?
two
151
Are topoisomerase II inhibitors cell cycle phase specific?
No
152
What cell cycle phase do topoisomerase II inhibitors have greater activity in?
G2/M
153
What is the suffix of anthracyclines?
-rubicin
154
What are side effects of doxorubicin?
-cardiotoxicity
-local tissue damage
155
What drug mediates cardiotoxicity associated with anthracyclines?
dexrazoxane
156
How is etoposide different than anthracyclines?
not an intercalator
157
What cell cycle phase does etoposide target?
G2
158
What is a resistance mechanism for topoisomerase II inhibitors?
increased DNA damage repair
159
What cell cycle phases does bleomycin target?
G2/M
160
What is a side effect of bleomycin?
myelosuppression
161
What is a dose-limiting side effect of bleomycin?
pulmonary side effects
162
What is the mechanism of action of vinka alkaloids?
prevent microtubule assembly
163
What is the mechanism of action of taxanes?
prevent microtubule disassembly
164
What is a side effect of vinka alkaloids?
peripheral neuropathy
165
What are side effects of vincristine?
-local inflammation
-myleosuppression
166
What is a dose-limiting side effect of vincristine?
neurotoxicity
167
How is eribulin beneficial compared to vincristine?
lower rate of neurotoxicity
168
What is the suffix of taxanes?
-taxel
169
What is a side effect of paclitaxel?
neurotoxicity
170
What is a dose-limiting side effect of paclitaxel?
myelosuppression
171
What is a clinical pearl of ixabepilone?
not cross-resistant with taxanes
172
What is the mechanism of action of pembrolizumab?
PD-1 inhibitor
173
What are the indications for pembrolizumab?
-advanced metastatic melanoma after treatment with ipilimumab and BRAF inhibitor
-PD-L1+ NSCLC
174
What is the mechanism of action of atezolizumab?
PD-L1 inhibitor
175
What is the mechanism of action of ipilimumab?
binds to CTLA-4 receptor and reverses CTL inhibition
176
What is the indication of ipilimumab?
advanced metastatic melanoma
177
What are side effects of ipilimumab?
-enterocolitis
-hepatitis
-dermatitis
-neuropathy
-endocrinopathy
178
What is the mechanism of action of trastuzumab and pertuzumab?
recombinant humanized monoclonal antibody specific for HER2
179
What is the indication of trastuzumab?
HER2+ breast cancer
180
What are side effects of trastuzumab?
-flu-like symptoms
-risk of cardiomyopathy/CHF
-risk of hypersensitivity reactions
181
What region of HER2 does trastuzumab bind to?
region IV
182
What region of HER2 does pertuzumab bind to?
region II
183
What is the mechanism of action of cetuximab?
recombinant chimeric monoclonal antibody specific for EGFR
184
What are the indications of cetuximab?
-colorectal cancer
-head and neck cancer
185
What are side effects of cetuximab?
-infusion reaction
-acneiform rash
-fatigue
-fever
186
What is the mechanism of action of bevacizumab?
recombinant humanized monoclonal antibody specific for VEGF
187
What is the indication of bevacizumab?
metastatic colorectal cancer in combination with 5-FU
188
What does bevacizumab bind?
VEGF ligand
189
What does ramucirumab bind?
VEGF receptor
190
What is the mechanism of action of rituximab?
CD20 antibody
191
What is the indication of rituximab?
B-cell lymphomas
192
What is the mechanism of action of daratumumab?
CD38 antibody
193
What is the indication of daratumumab?
multiple myeloma
