Cancer Treatment Modalities: Biotherapy (Immunotherapy and Targeted Therapy) Flashcards
1
Q
Biotherapy =
A
Any form of treatment that uses the body’s natural abilities, or made from living organisms/lab to fight invading organisms, disease processes, or effects of treatment
2
Q
Difference between biotherapy and chemotherapy =
A
Focus on body’s biologic role in tumor development or its response to a tumor or treatment (indirectly acts on immune system) vs. cytotoxic chemo affects all cells not just tumor cells
3
Q
Targeted therapy =
A
Treatment that uses drugs or other substances to identify and attack specific cancer cells with less harm to normal cells
- some block action of certain enzymes, proteins, molecules involved in growth and spread of cancer cells
4
Q
Immunotherapy =
A
Uses substances to stimulate or suppress immune system to help body fight cancer, infection, diseases
5
Q
Growth signal inhibitors, Angiogenesis inhibitors, Apoptosis inducing drugs are all examples of?
A
Targeted therapy
6
Q
Types of biotherapy (2)
A
Immunotherapy
Targeted therapy
7
Q
Immunotherapy works by? (3)
A
1) Boost immune system
2) Enable immune system to
3) Recognize and fight tumor
Stop or slow cancer growth
8
Q
Classes of immunotherapy (5)
A
1) Monoclonal antibodies
2) Vaccines
3) Cytokines
4) Adoptive cell therapy
5) Checkpoint inhibitors
9
Q
Cytokines =
A
Hormone-like proteins with low molecular weight that are secreted by various cell types, which regulate intensity and duration of immune response and mediate cell to cell communication
10
Q
Classes of Cytokines (3)
A
1) CSFs, HGFs, GCSFs
2) Interferons (IFN alpha 2a, beta 1a, beta 1b, gamma 1b)
3) Interleukins (ILs)
11
Q
Mechanism of action of Interferons (INFs) =
A
Slows growth of cancer cells and encouraging normal cell behavior (naturally occurring substances in body)
12
Q
Potential SE of Interferons (IFNs)
A
- Flu like sx
- Fatigue, Anorexia
- Neuropsychiatric sx
- Electrolyte disturbance
13
Q
Example of an interleukin
A
IL-2
14
Q
Mechanism of action of interleukins =
A
T cell growth factor
Stimulates growth of natural killer NK cells and cytotoxic T cells to enhance antibody response by binding to receptors on surface of T cells
15
Q
Potential SE of Interleukins
A
- Capillary leak syndrome
- Hypotension
- Infusion reactions, rigors, chills, muscle pain, fever, SOB, skin rash/flushing
- Cardiac arrhythmia
- Diarrhea
16
Q
Cancer Vaccines =
A
Treat existing* cancers or prevent development of cancer by boosting immune system
17
Q
Cancer prevention (prophylactic) vaccines (2)
A
Hepatitis B vaccine -> prevents liver cancer
Human papillomavirus (HPVP -> prevents cervical cancer
18
Q
Cancer treatment (therapeutic) vaccines (2)
A
Sipuleucel T -> hormone refractory prostate CA
Talimogene laherparepvec -> metastatic melanoma
19
Q
Monoclonal antibodies =
A
Antibodies made in lab that target tumor specific antigens which are proteins that some tumors have
Can make many copies of that antibody hence monoclonal (mAbs)
20
Q
What does it mean that mAbs are passive?
A
Do not result in any immunologic memory
21
Q
3 most common monoclonal antibodies
A
Rituximab
Trastuzumab
Bevacizumab
22
Q
How do mAbs work? (3)
A
1) Flag cancer cells for destruction
2) Block growth signals and receptors
3) Deliver other anticancer agents to site of tumor (when they are bound to other drugs or radiation particles, cancer cell engulfs and digests the mAb, attached chemo/radiation induces cellular death
23
Q
Where are mAbs derived from before they get to the lab? Whose antibodies?
A
Human antibodies, animal antibodies, or a combination of the two
24
Q
Types of mAbs derived from antibodies of
1) mouse
2) mouse and human
3) predominantly human
4) human only
A
1) Murine
2) Chimeric
3) Humanized
4) Human
25
Which antigens do these naked MOABS (those that can work alone) target?
1) Alemtuzumab (campath)
2) Trastuzumab (Herceptin)
3) Rituximab
4) Tositumomab
5) Obinutuzimab
6) Imatinib mesylate
1) CD52, CD20
2) HER2
3) CD20
4) CD20
5) CD20
6) Philadelphia chromosome
26
Mechanism of action of MOABS
Attaches to antigens expressed by specific cancer cells, acting as a marker for body's immune system to destroy the cells
27
Antiangiogenic (anti-vascular endothelial growth factor) VEGF naked MOab agents =
Moabs that target the vascular endothelial growth factors that affects and may cause excessive tumor blood vessel growth (angiogenesis)
28
Examples of Antiangiogenic MOABS
```
Bevacizumab (Avastin)
Pazopanib
Sunitinib
Sorafenib
Axitinib
Vandetanib
```
29
MoAb that treats CLL
Alemtuzumab (Campath) binds to CD52 antigen
30
MoAb that treats breast and stomach cancers that have antigen HER2
Trastuzumab (Herceptin)
31
Conjugated mAbs (2) =
| tagged, labeled, loaded antibodies
mAbs combined with chemotherapy or radioactive particles
Radiolabeled antibodies
Chemolabeled antibodies
32
Ibritumomab tiuxetan (Zevalin) =
Radiolabeled mAb,
Targets CD20 antigen found on B lymphocytes
Tx for refractory or relapsed B Cell NHL
made of rituximab and radioactive substance (Yttrium-90)
33
Brentuximab Vedotin (Adcetris) =
Chemolabeled mAb
Targets CD30 antigen found on lymphocytes
Tx for refractory Hodgkin Lymphoma
34
Ado-Tastuzumab emtansine (Kadcyla, TDM-1) =
Chemolabeled mAb
Targets HER2 protein for Metastatic Breast CA
Attached to chemo drug DM1
35
Bispecific monoclonal antibodies =
Made up of 2 different mAbs -> can attach to 2 different proteins at the same time
36
Blinatumomab (Blincyto)
Bispecific mAb
Targets CD19 protein found on some leukemia and lymphoma cells and CD3 found on T cells
37
Cetuximab (Erbitux) =
Chimeric mouse and human antibody
Targets cell protein EGFR (epithelial growth factor receptor)
38
Adoptive T-Cell Transfer =
CAR-T cell
Collecting T cells which play a primary role in how immune system fights cancer from a patient and engineering them to recognize specific antigens on the surface of cancer cells -> then infusing them back into patient
39
Two major side effects of CAR-T cell therapy
Cytokine release syndrome
Neuro toxicities
40
Immune checkpoints =
Traffic lights that prevent over-activation of immune response (attack on healthy cells)
Key component of a healthy immune system
41
Examples of checkpoints on the surface of immune cells (3)
1) Programmed cell death protein (PD-1)
2) Programmed death ligand (PD-L1)
3) Cytotoxic T lymphocyte-associated protein 4 (CTLA-4)
42
Checkpoint inhibitors are a subset of?
mAbs
43
How do checkpoint inhibitors work on cancer?
release breaks on the immune system making it more likely to respond to tumor cells -> enhances T cell activity against tumor cells
44
Dose reductions are not possible with what immunotherapy?
Checkpoint inhibitors
45
irAEs =
Immune related adverse events
46
Most frequently cite iRAEs in clinical trials involving what 3 drugs?
Ipilimumab
Nivolumab
Pembrolizumab
47
Adverse effects of Ipilimumab
Fatigue
Diarrhea, colitis, enterocolitis
Hepatitis
48
Adverse effects of Nivolumab
```
Fatigue/musculoskeletal pain
Pruritis
Pneumonitis**
Colitis
Hepatitis*
Endocrinopathies, hypophysitis (inflammation of pituitary gland), diabetes mellitus
```
49
Adverse effects of Pembrolizumab
Fatigue
Endocrinopathies, hypophysitis, diabetes mellitus
Pneumonitis
Hepatitis*
50
Because of the most common iRAEs what lab test should patients get?
Liver function tests
51
Risk for iRAEs may directly correlate with high level expression of what checkpoint inhibitor on tumor cells?
PD-L1
52
irAEs typically present when after initiating therapy?
6-12 weeks
53
irAES cited most frequently in dermatologic and gastrointestinal areas why?
Immune cells are most active in those areas
54
Targeted therapy =
Uses information about persons genes and proteins to target only a single or multiple abnormal protein on cancer cells without damaging normal cells
55
Targeted therapies work by (3)
1) Blocking angiogenesis
2) Blocking signals inside or outside the cell
3) Delivering toxic substances to the cell
56
Why is targeted therapy not always effective even though its suppose to work on your specific cancer?
Having the target does not mean the tumor will respond to the drug
57
Difference between targeted therapy and chemotherapy?
Chemotherapy is cytotoxic whereas targeted therapy is cytostatic (blocks tumor cell proliferation)
58
Types of Targeted therapy
```
Signal Transduction Inhibitors
Tumor Specific Antigens
Apoptosis Inducers
Angiogenesis Inhibitors
Small Molecule Agents
Targeted Therapy
```
59
Signal Transduction Inhibitors =
Targeted therapy that blocks signal transduction that regulates cell growth, function, and apoptosis
60
Cell signals that come from outside the cell =
growth factors and growth factor receptors
61
Cell signals that come from inside the cell =
tyrosine kinase receptors
62
Process of cell signaling
Signal is transmitted by _____ to the cell's control ____ (____) through a series of biochemical _____. Control center ____ these signals and produces an appropriate _____. Activation of ____ ___ triggers biochemical ____ of cell signaling events. In cancer these signals are _____ "on" and malignant cells are stimulated to _____ continuously without being prompted by outside signals.
```
proteins
center (nucleus)
reactions, reads
response
tyrosine kinases
cascade
stuck
divide
```
63
Examples of signal transduction inhibitors used in treatment of cancer (5)
```
EGFR inhibitors
HER2 inhibitors
BCR-ABL (tyrosine kinase) inhibitors
ALK (multikinase) inhibitors
BRAF inhibitors
```
64
Examples of drugs that block the following signal transduction inhibitors
1) EGFR inhibitors
2) HER2 inhibitors
3) BCR-ABL (tyrosine kinase) inhibitors
4) ALK (multikinase) inhibitors
5) BRAF (multikinase) inhibitors
1) Cetuximab, Erlotinib
2) Trastuzumab, Pertuzumab
3) Imatinib, Dasatinib
4) Crizotinib, Certinib
5) Vemurafenib, Dabrafenib
65
Tumor specific antigen =
A protein or other molecule that is unique to cancer cells or is much more abundant in them
66
Tumor specific antigens are usually found in what part of the cell?
Plasma (outer) membrane
67
For a tumor antigen to be best suited for targeted therapy it should be
1) _____ to tumor cells
2) Located on the _____ of tumor cells
3) Present in ____ numbers
4) Involved in tumor cell _____
1) Specific
2) Surface
3) large
4) survival
68
Tumor specific antigens are very important in treating what types of cancers?
Leukemia, Lymphomas
69
CD20 =
Found on normal and malignant pre-B lymphocytes and mature B lymphocytes
Tx for certain types of B cell lymphomas and leukemia
70
What drug targets and destroys B cells that have CD20?
Rituximab
71
CD33 =
Found on myeloid (myeloid specific) cells but also some lymphoid
Tx for AML
72
CD52 =
A protein present on surface of mature lymphocytes but not on stem cells from which these lymphocytes were derived; also found on monocytes and dendritic cells associated with some types of lymphoma
Tx for some types of lymphoma
73
Drug that targets CD52, marking the CD52 lymphocytes for destruction =
Alemtuzumab
74
The CD Antigens (3)
CD20
CD52
CD33
75
Apoptosis Inducers =
Cause cancer cells to undergo apoptosis
76
Proteasome inhibitor =
An apoptosis inducer that stops proteasome from breaking down proteins that cause cell death -> cell death
77
What is a proteasome?
A complex of enzymes inside a cell that helps destroy proteins no longer needed by the cell
78
Bortezomib and Carfilzomib are examples of?
Apoptosis inducers
79
Angiogenesis Inhibitors =
Block tumor angiogenesis where tumors create their own blood supply needed for growth and metastasize
80
Two ways to inhibit tumor angiogenesis
1) Inhibit the action of what protein or receptor?
2) Target ____ on the surface of ____ cells or other proteins in downstream signaling pathways that stimulate a new blood ____ growth
1) Vascular endothelial growth factor (VEGF)
| 2) receptors, endothelial, vessel
81
Popular Angiogenesis Inhibitors (3)
Bevacizumab
| Sorafenib and Sunitinib
82
Bevacizumab =
An Angiogenesis inhibitor that specifically recognizes and binds to VEGF
Tx for Metastatic Colorectal Ca
Bad for wound healing
83
Sorafenib and Sunitinib =
Angiogenesis inhibitors that bind to receptors on surface of endothelial cells or to other proteins in downstream signaling pathways, blocking their activities
84
Small molecule targeted therapies =
Developed for targets that are located inside* the cell (intracellular) because these agents are able to enter cells more easily -> disrupts function of cells, causing cell death
85
Examples of Small Molecule Agents (5)
1) Tyrosine Kinase Inhibitors (TKIs)
2) Tyrosine Kinase inhibiting MOABS
3) Kinase inhibitors
4) P13K inhibitors
5) Hedgehog pathway inhibitors
86
TKIs and Tyrosine Kinase Inhibiting MOABS
1) Which antigen is targeted?
2) Examples (7)
3) Mechanism of action:
1) Epidermal Growth Factor Receptor (EGFR)
2) END IN TINIB* for TKI
Cetuximab, Gefitinib, Erlotinib, Lapatinib, Panitumumab, Vandetanib, Zivaflibercept
3) TKIs bind to tyrosine kinase in EGFR -> inactivating or limiting its activity
87
How do monoclonal antibodies with TKI capabilities work?
They bind to extracellular component of EGFR to prevent actual substrates from binding to receptors, inhibiting EGFR activation
88
TKI drug route =
So those administering should be aware of
1) A____ to therapy
2) Interactions with:
Oral agents
1) Adherence
2) food/drug and drug/drug that influences when to take and what food/drink to avoid
89
Examples of TKIs
End in Tinib*
```
Erlotinib
Sunitinib
Ponatinib
Imatinib
Dasatinib
Ibrutinib
```
90
TKIs and the cancers they treat
1) Erlotinib
2) Sunitinib
3) Ponatinib
4) Imatinib
5) Dasatinib
6) Ibrutinib
1) Advanced NSLCA and pancreatic CA
2) Advanced RCC, GIST (gastrointestingal stromal tumors)
3) CML
4) Philadelphia chromosome + CML
5) Philadelphia chromosome + CML
6) Mantle cell lymphoma, Waldenstroms macroglobulinemia, CML
91
Kinase Inhibitors
1) What is it?
2) Target what pathway?
3) Drug names end in?
4) Nursing considerations:
1) Type of Small Molecule Agent Targeted Therapy
2) RAF/RAS/MET pathway
3) nib
4) Oral agent -> be aware of drug/food interactions, when to take, foods to avoid
92
Examples of Kinase Inhibitors
Sorafenib
Dabrafenib
Trametinib
Vemurafenib
93
P13K Inhibitors
1) What is it?
2) Targets what pathway?
3) Drug names end in?
4) Nursing considerations:
1) Small molecule agent targeted therapy
2) P13K pathway
3) Lisib
4) Oral agent -> food/drug interactions, when to take, foods to avoid
94
Idelalisib =
Treats what? (2)
P13K inhibitor
1) Follicular B cell non-Hodgkin Lymphoma
2) Relapsed CLL
95
What is the Hedgehog pathway?
Aberrant signaling of this pathway leads to?
Plays a role in brain and spinal cord development and controls cell division and differentiation in adult stem cells
Different forms of cancer
Therefore, targeting this pathway may prevent/treat cancers
96
Hedgehog pathway inhibitors
1) What is it?
2) Drug names end in?
3) Nursing considerations:
1) Small molecule agent targeted therapy
2) Gib
3) oral agent -> food/drug interactions, when to take, what foods to avoid
97
Sonidegib and Vismodegib =
What conditions do they treat?
Hedgehog pathway inhibitors
Locally advanced basal cell carcinoma
Metastatic or recurrent local advanced basal cell carcinoma
98
Targeted therapy main side effects (5)
```
Infusion reaction/hypersensitivity
Skin reactions
Cardiovascular effects
Bleeding and clotting abnormalities
Impaired wound healing
```
Other SE
N/V, diarrhea/constipation, mucositis, cough, dyspnea, fatigue, HA, edema, organ toxicity, colitis, risk for infection
99
Hormone therapy =
Treatment that adds, blocks, removes hormones from body to help slow or stop growth of cancer cells
100
What are hormones? Where are they produced?
The body's chemical messengers
Endocrine glands (thyroid, pancreas, ovaries, testes)
101
What type of cancers do hormone therapies usually treat?
Breast and Prostate
| usually used with chemo/RT
102
Hormone therapy mechanisms of action (3)
1) Block hormone receptors
2) Blocks the body's production of the hormone
3) Eliminates or changes shape of hormone receptors on cell surface
103
Examples of Hormone therapy drugs (4)
1) Antiestrogens (tamoxifen, fulvestrant)
2) Aromatase inhibitors (Anastrozole, exemestane)
3) Antiadrogens (Biculatamide, Flutamide)
4) Luteinizing hormone releasing hormone (LHRH) agonist (Goserelin, leuprolide)
