PCol of Chemo Flashcards
How do Small Molecule Inhibitors work?
A. Block the growth factor receptor at the receptor site
B. Block an allosteric site on growth factor receptors
C. Block tyrosine kinase activity at the receptor site or away from the receptor site
D. Irreversibly bind to the receptor binding site and prevent ligand interaction
C. Block tyrosine kinase activity at the receptor site or away from the receptor site
As you can see in the picture the medications are working at the level of the tyrosine kinases and NOT at the receptor binding site
How do Monoclonal Antibodies work? (Select all)
A. Directly inhibits binding site at the growth factor receptor
B. Directly inhibits tyrosine kinases within the cell
C. Directly binds to allosteric sites on growth factor receptors
D. Binds to the natural ligand of a growth factor receptor
A. Directly inhibits binding site at the growth factor receptor
D. Binds to the natural ligand of a growth factor receptor
Monoclonal antibodies can bind to the growth factor receptor site such as EGFR (Epidermal Growth Factor Receptors) or it can bind directlyl to the ligand responsible for activating the growth (factor receptor. An example of this would be VEGF (Vascular Endothelial Growth Factor) being bound to the monoclonal antibody and being unable to bind to its VEGFR receptor now.
Which of these medications is a mono-clonal antibody? (select all)
A. Gefitnib
B. Trastuzumab
C. Lapatinib
D. Panitumumab
E. Certuximab
B. Trastuzumab
D. Panitumumab
E. Certuximab
Mab= mono clonal antibody
Which of these medications is a Small Molecule Inhibitor? (select all)
A. Gefitnib
B. Lapatinib
C. Pertuzumab
D. Erlotinib
E. Trastuzumab
A. Gefitnib
B. Lapatinib
D. Erlotinib
nib= small molecule inhibitor
I think of nibble as in small bites
Which of these medications are categorized as Growth Factor Receptor Antagonists? (select all)
A. Gefitinib
B. Trastuzumab
C. Imatinib
D. Panitumumab
E. Certuximab
A. Gefitinib- EGFR kinases
B. Trastuzumab- HER-2
D. Panitumumab-EGFR
E. Certuximab- EGFR
Which of these medications competitivelyl inhibits EGFR tyrosine kinases? (Select All)
A. Gefitinib
B. Trastuzumab
C. Imatinib
D. Erlotinib
E. Lapatinib
A. Gefitinib
D. Erlotinib
E. Lapatinib
Which of the following is a mechanism of resistance to Gefitinib? (Select All)
A. Tumors that are not uniquely dependent on EGFR
B. Poor drug penetration
C. Drug efflux mechanisms
D. Tumor mutates to only rely on EGFR overexpression to achieve cellular growth
E. T790M mutation
D. Tumor mutates to only rely on EGFR overexpression to achieve cellular growth
The previous mechanisms are all mechanisms of ressitance except for this one. Gifitnib was found to be very beneficial in patients who overexpressed EGFR (mutation) because the drug works at the EGFR tyrosine kinases and blocks them from phosphorylating. So if the tumor only relies on EGFR for replication then this is not a mechanism of resistance against this particular drug, Gefitinib.
What is the MOA of Gefitinib? (select all)
A. Competitive inhibitor of EGFR tyrosine kinase
B. Prevention of ATP phosphorylation
C. Cell cycle arrest at the G0/G1 boundary
D. Binds to the EGF ligand and prevents its binding to the EGFR receptor
E. Binds to the receptor pocket of EGFR and prevents ligand binding and activation
A. Competitive inhibitor of EGFR tyrosine kinase
B. Prevention of ATP phosphorylation
C. Cell cycle arrest at the G0/G1 boundary
Remember that Gefitinib is a small molecule inhibitor meaning that it binds competitively to the EGFR tyrosine kinase. It is competeing with ATP for that tyrosine kinase binding pocket so if Gefitnib binds to that binding pocket instead of ATP then phosphorylation cannot happen. if there is no phosphorylation then the kinase pathway cannot be activated and the cell cycle will be arrested.
Gefitinib works well in patients with:
A. T790M gene mutation
B. Underexpressed EGFR
C. Overexpressed EGFR
D. Mutated EGFR with altered tyrosine kinases
C. Overexpressed EGFR
Since Gefitinib works at the tyrosine kinases of EGFR receptors then an overexpressed EGFR receptors will be succeptible to GIfitnib since it is able to block phosphorylation at the level of the kinases.
Which of these mutations can a tumor undergo that will actually increase Gefitinib activity responsiveness? (Select All)
A. L858R Tyrosine Kinase mutation
B. T790M Tyrosine Kinase mutation
C. d746:753 Tyrosine Kinase mutation
D. TLK58 Tyrosine Kinase mutation
A. L858R Tyrosine Kinase Mutation
C. d746:753 Tyrosine Kinase Mutation
T790M is actually a tyrosine kinase mutation that Gefitnib AND Erlotinib have less of an effect on. They are mechanisms of resistance.
T/F
Erlotinib is inneffective against the tyrosine kinase mutation T790M
T
Which of the following receptor tyrosine kinases is inhibited by Lapatinib? (select all)
A. ErbB1 (EGFR)
B. HER-3
C. ErbB2 (HER-2)
D. ErbB3
A. ErbB1 (EGFR)
B. ErbB2(HER-2)
Which of the following statments is true regarding HER-2 (ErbB-2)?
A. Generates a weaker signaling cascade when it dimerizes with another HER-2 receptor
B. Generates a weaker signaling cascade when it dimerizes with an EGFR receptor that is bound to an EGF.
C. Generates a much stronger signaling cascade when it binds to the ligand EGF and dimerizes with another HER-2
D. Generates a much stronger signaling cascade when it dimerizes with an EGFR receptor that is bound to an EGF.
D. Generates a much stronger signaling cascade when it dimerizes with an EGFR receptor that is bound to an EGF.
HER receptors do not bind directly with EGF. Instead they will dimerize with an EGFR receptor that already has EGF bound to it. When HER and EGFR dimerize they will produce a much stronger signaling cascade that drives cellular replication in comparison to an EGFR receptor dimerizing with another EGFR receptor. Thats what makes HER-2 receptors so dangerous and problematic.
T/F
HER-2 Receptors are constituitvelyl (always) expressed in normal cells.
False
HER-2 receptors are typically only expressed in breast tumors. In other words something has to happen to the cell that causes it to express that type of receptor.
Which of these medications is a monoclonal antibody that blocks EGFR receptor kinases? (Select All)
A. Certuximab
B. Trastuzumab
C. Pertuzumab
D. Panibumumab
A. Certuximab
D. Panibumumab
Which of these Small Molecule inhibitors blocks EGFR ONLY? (Select All)
A. Gefitinib
B. Lapatinib
C. Erlotinib
D. Certuximab
A. Gefitinib
C. Erlotinib
Lapatinib does block EGFR BUT it also blocks HER-2.
Which of these Monoclonal antibodies blocks HER-2 receptors? (Select All)
A. Certuximab
B. Trastuzumab
C. Panitumumab
D. Pertuzumab
B. Trastuzumab
D. Pertuzumab
Which of these Small Molecule Inhibitors blocks both EGFR and HER-2?
A. Gefitinib
B. Erlotinib
C. Lapatinib
D. Pertuzumab
C. Lapatinib
Which of the following Growth Factor Receptor Antagonists has the ability to block ONLY EGFR (Select All)
A. Gefitinib
B. Cetuximab
C. Erlotinib
D. Pertuzumab
E. Lapatinib
F. Panitumumab
A. Gefitinib
B. Cetuximab
C. Erlotinib
D. Panitumumab
Which of the following Growth Factor Receptor Antagonists is able to block either HER-2 receptors or HER-2 receptor kinases? (Select All)
A. Lapatinib
B. Erlotinib
C. Cetuximab
D. Trastuzumab
E. Pertuzumab
A. Lapatinib
D. Trastuzumab
E. Pertuzumab
Both Cetuximab and Panitumumab are are monoclonal antibodies that block EGFR. The advantage of Panitumumab is that it is ___.
A. Chimeric
B. Humanized
C. Human
D. Animal
C. Human
Here is a chart that summarizes how you can tell the difference between chimeric, humanized and human
T/F
The advantage of Certuximab has over Panitumumab is that a patient taking certuximab will have less of an allergic response in comparison to a patient taking Panitumumab
False
Certuximab is chimeric so it is not completely human like Panitumumab is. The more human-like the monoclonal antibody is the less likely it will produce an allergic response in the patient.
Which of the following statments is true regarding Trastuzumab? (Select All)
A. Chimeric mouse/human monoclonal antibody
B. Binds to EGFR receptors
C. Binds to HER-2 receptors
D. Can induce antibody-dependent cellular cytotoxicity
E. Can inhibit angiogenesis
A. Chimeric mouse/human monoclonal antibody
C. Binds to HER-2 receptors
D. Can induce antibody-dependent cellular cytotoxicity
E. Can inhibit angiogenesis (she mentioned this)
Antibody-dependent cellular cytotoxicity is possible because the monoclonal antibody binds to the HER-2 receptors and targets the cell for destruction by natural cytotoxic cells in the body. This is it’s additional function but its primary function is that it disrupts receptor cell signaling to stop cellular replication.
What is the main clinical toxicity of Trastuzumab that requires a baseline test before administration of the drug?
A. Nephrotoxicity
B. Hepatotoxicity
C. Neurotoxicity
D. Cardiotoxicity
D. Cardiotoxicity
This especially can occur if given with anthracyclines
Which other monoclonal antibody is Pertuzumab sometimes used in conjunction with?
A. Certuximab
B. Trastuzumab
C. Panitumumab
D. Gefitinib
B. Trastuzumab
The way I remember this is that they are the only two monoclonal antibodies that bind to HER-2 receptors so they can be used in conjunction.
Why is Pertuzumab used in conjunction with Trastuzumab?
A. Pertuzumab blocks EGFR receptors only and Trastuzumab blocks HER-2 receptors only.
B. Pertuzumab blocks HER-2 receptors only and Trastuzumab blocks EGFR receptors only.
C. Pertuzumab and Trastuzumab both bind at different target regions of the EGFR receptor and therefore complement each others activity at the receptor.
D. Pertuzumab and Trastuzumab both bind at different target regions of the HER-2 receptor and therefore complement each others activity at the receptor.
D. Pertuzumab and Trastuzumab both bind at different target regions of the HER-2 receptor and therefore complement each others activity at the receptor.
Increased toxicity is reported when giving Erlotinib or Gefitnib with CYP3A4 ___.
A. Inducers
B. Inhibitors
B. Inhibitors
CYP3A4 is the major metabolic pathway for Erlotinib and Gefitinib so blocking the enzyme will cause accumulation of the drug and cause toxicity.
Which of these Small Molecule Inhibitors is meant to block ABL? (Select All)
A. Imatinib
B. Dasatinib
C. Gefitinib
D. Erlotinib
E. Nilotinib
A. Imatinib
B. Dasatinib
E. Nilotinib
When going through the answer choices be sure to identify as much as you can about each drug that is the wrong answer to refresh your knowledge.
Which of these Small Molecule Inhibitors is meant to block ABL? (Select All)
A. Lapatinib
B. Dasatinib
C. Bosutinib
D. Erlotinib
E. Ponatinib
F. imatinib
B. Dasatinib
C. Bosubinib
E. Ponatinib
F. Imatinib
Which of these Small Molecule Inhibitors is better suited to bind to Wild-Type ABL? (Select All)
A. Imatinib
B. Bosutinib
C. Nilotinib
D. Dasatinib
E. Ponatinib
C. Nilotinib
D. Dasatinib
Which of the following is true regrding the medication Imatinib? (Select All)
A. Inhibits ABL and BCR-ABL
B. Binds at the ATP binding site on ABL
C. Stablizes the ABL in an open (inactive) conformation
D. Inhibits PDGFR
E. Inhibits KIT
A. Inhibits ABL and BCR-ABL
B. Binds at the ATP binding site on ABL
D. Inhibits PDGFR
E. Inhibits KIT
It stabilizes the ABL in the closed inactive state NOT the open state.
Which of the following statments is true regarding KIT? (Select All)
A. Its oncogene is called C-Kit
B. Its oncogene can cause higher incidence of Gastrointestinal Stromal Tumors (GIT or GIST)
C. Uses EGF as its ligand for activation
D. Kit is a cytokine receptor expressed on hematopoietic stem cells
E. Requires Stem Cell factor as its ligand for activation
A. Its oncogene is called C-Kit
B. Its oncogene can cause higher incidence of Gastrointestinal Stromal Tumors (GIT or GIST)
D. Kit is a cytokine receptor expressed on hematopoietic stem cells
E. Requires stem cell factor and its ligand for activation.
Imatinib uses CYP3A4 as its major form of metabolism. We can expect to see toxicities when this medication is given with CYP3A4___.
A. Inhibitors
B. Inducers
A. Inhibitors
Which of these are clinical toxicities of Imatinib? (Select All)
A. Neutropenia
B. Hepatotoxicity
C. Neurotoxicity
D. Thrombocytopenia
A. Neutropenia
D. Thrombocytopenia
Which of the following are advantages of Bosutinib and Ponatinib in comparison to Imatinib?
A. Bosutinib and Ponatinib have greater affinity for the Variant-Type BCR-ABL
B. Bosutinib and Ponatinib have greater affinity for the Wild-Type BCR-ABL
C. Bosutinib and Ponatinib are able to inhibit the T790 gene variant of BCR-ABL
D. Bosutinib and Ponatinib are able to inhibit VEGFR kinases as well.
A. Bosutinib and Ponatinib have greater affinity for the Variant-Type BCR-ABL
What is the distinc advantage Ponatinib has over the other BCR-ABL kinase inhibitors?
A. Inhibits the T790M Variant-gene of ABL
B. Inhibits angiogenesis
C. Inhibits the T315I mutant ABL
D. Has increase binding affinity for the Wild-Type BCR-ABL
C. Inhibits the T315I mutant ABL
What is the MOA of Everolimus?
A. Inhibition of RAF-C
B. Inhibition of RAF-B
C. Inhibition of EGFR kinases
D. Inhibition of RAS
E. Inhibition of mTOR
E. Inhibtion of mTOR
Which of the following medications is a Proteosome Inhibitor?
A. Sorafenib
B. Gefitinib
C. Trastuzumab
D. Bortezomib
D. Bortezomib
What is the overall effect of using a proteosome inhibitor? (Select All)
A. Preventing the degredation of pro-apoptotic factors
B. Increasein Neoplastic cell degredation via apoptosis
C. Increases the turnover rate of cells in the cell cycle
D. Decreases the affinity of neoplastic cell degredation
A. Preventing the degredation of pro-apoptotic factors
B. Increasein Neoplastic cell degredation via apoptosis
Which of the following stimulates the production of VEGF? (Select All)
A. Cytokines
B. Over-oxygenation
C. Body’s natural homeostasis
D. Hypoxia
E. Growth factors
F. Oncogenes
A. Cytokines
D. Hypoxia
E. Growth Factors
F. Oncogenes
Which of these proteins is responsible for regulating the amount of VEGF that is produced?
A. VHS
B. VHL
C. VEO
D. VOL
B. VHL (Von-Hippel Lindau protein)
VHL is respnosible for ubiquitination of the transcription factor HIF-1a that codes for VEGF (as well as EPO). When HIF-1a is ubiquitinated by VHL protein it is targeted for proteosome destruction.
VHL is always expressed to regulate VEGF in times of normal bodily function. VHL is not active when the stimuli for VEGF production are present (cytokines, growth factor, hypoxia, oncogenes)
What is the suspected MOA of Bevacizumab when it bids to VEGF? (Select All)
A. Induction of tumor hypoxia and starvation
B. Generates large influx of oxygen and causes tumor cell to rupture
C. Increases delivery of chemotherapeutic medications, potentiating their effects
D. Increases affinity for kinases of other medications
A. Induction of tumor hypoxia and starvation
C. Increases delivery of chemotherapeutic medications, potentiating their effects
What is the common risk that all Angiogeneisis inhibitor share
A. Risk of clotting
B. Risk of bleeding
C. Risk of DVT
D. Risk of VTE
B. Risk of bleeding
Regorafenib is an Angiogenesis Inhibitor that is a Small Molecule Inhibitor that binds to: (Select All)
A. EGFR
B. TIE2-TK
C. VEGFR-2
D. PDGFR-B
B. TIE2-TK
C. VEGFR-2
How does Ziv-aflibercept prevent Angiogenesis?
A. Binds to VEGFR receptors at the binding site
B. Binds to the ligand VEGF-A and prevents it from reaching the target VEGFR receptor.
C. Binds to VEGFR kinases and prevent phosphorylation from occuring
D. None of the above
B. Binds to the ligand VEGF-A and prevents it from reaching the target VEGFR receptor.
Which of the following statements is true regarding bFGF is FALSE?
A. Resides in the sub-endothelial extracellular matrix of blood vessels
B. Stays membrane-bound until activated
C. During wound healing heparin sulfat-degrading enzymes activate bFGF
D. bFGF mediates the formation of new blood vessels.
E. bFGF is utilized by tumor cells in order to degrade blood vessels of the body, causing extensive bleeding.
E. bFGF is utilized by tumor cells in order to degrade blood vessels of the body, causing extensive bleeding.
Which of these Immune Checkpoint Inhibitors inhibits CTLA-4 receptors on T-Cells?
A. Ipilimumab
B. Pembrolizumab
C. Nivolumab
D. Rituximab
A. Ipilimumab
What is the possible MOA of tumor-specific monoclonal antibodies? (Select All)
A. Enhance binding to tumor-specific EGFR
B. Induction of antibody dependent cell-mediated cytotoxicity
C. Induction of apoptosis of the cancer cell
D. Enhance binding to tumor-specific EGFR kinases
B. Induction of antibody depenent cell-mediated cytotoxicity
C. Induction of apoptosis of the cancer cell
Rituximab binds to ___ receptors that are located on ___.
A. CD52, B-Cells
B. CD20, B-Cells
C. CD52, T-Cells
D. CD20, T-Cells
B. CD20, B-Cells
B-Cell lymphomas express CD20 on their cell surfaces so this medication will allow the binding to that receptor and help target the cancer cell for antibody-dependent cell-mediated cytotoxicity
Alemtuzumab binds to ___ receptors on ___ and ___ .
A. CD20, T-Cells and B-Cells
B. CD54, T-Cells and B-Cells
C. CD20, T-Cells and Dendritic cells
D. CD54, T-Cells and Dendritic cells
B. CD54, T-Cells and B-Cells
