Brainscape's Knowledge GenomeTM


Top Flashcards (Certified)
All Flashcards

PHAR 359 > Targeted Therapies > Flashcards

Targeted Therapies Flashcards

1
Q

What is personalized medicine?

A

Development and use of targeted therapy specifically in individuals known to have the mutation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Hormone treatments are used in which cancers? (5)

A
  1. Breast
  2. Endometrial
  3. Ovarian
  4. Uterine sarcomas
  5. Prostate
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What are the major breast cancer hormonal treatment drugs to know? (5)

A
  1. Tamoxifen
  2. Aromatase Inhibitors
    - Anastrozole
    - Exemestane
    - Letrozole
  3. Goserelin acetate (Zoladex) - GnRH agonist
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What class is Tamoxifen?
How does it act in breast tissue and endometrium? (2)

A
  1. Tamoxifen is a Selective Estrogen Receptor Modulator (SERM)
  2. Estrogen antagonist in breast tissue
  3. Estrogen agonist in endometrium
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What is the MOA of Tamoxifen? (4)

A
  1. Estrogen enters the cell and binds to an estrogen receptor
  2. The receptor binds to DNA which triggers cell proliferation
  3. Tamoxifen enters a cancer cell and binds to estrogen receptors
  4. When estrogen enters the cell, it can’t bind to the receptors. Cancer cell proliferation is prevented
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What are 2 settings in which Tamoxifen is used?

A

Used in the adjuvant (curative) and metastatic (not curative) settings for hormone receptor (ER or PR) positive breast cancers

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What is the dosing of Tamoxifen?

A

20mg PO once daily
(No indication that going higher is more effective)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

How long is Tamoxifen typically used?

A

5 years - sometimes 10 years when high risk patient

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What are we using instead of Tamoxifen in postmenopausal women with breast cancer?

A

Aromatase inhibitors
(May also be used in premenopause IF ovarian function is suppressed)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What are the side effects of Tamoxifen? (8)

A
  1. Flushing, hot flashes!!!!
  2. Hypertension
  3. Skin rash
  4. Fluid retention
  5. Nausea 5-26% – recommend to take at night to sleep through; should improve as body adjusts
  6. Mood changes – depression, fatigue
  7. Arthralgia, arthritis
  8. Vaginal discharge or dryness
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What are the serious side effects of Tamoxifen? (2)

A
  1. DVT- PE - stroke
  2. Uterine cancer
    These risks were increased particularly in women on tamoxifen who were 50 years of age or older
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What CYP enzymes interact with Tamoxifen?

A

2D6 and 3A4

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What is a drug-drug interaction to be aware of with Tamoxifen?

A

Anticoagulants - increased risk of bleeds

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What is a drug-food interaction to be aware of with Tamoxifen?

A

Grapefruit juice - inhibits 3A4 which increases Tamoxifen levels

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What is the MOA of aromatase inhibitors? (2)

A
  1. A potent and selective nonsteroidal aromatase inhibitor
  2. Prevents conversion of androstenedione to estrone and conversion of testosterone to estradiol
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

AIs are considered treatment of choice for what?

A

Adjuvant hormonal therapy to lower the risk of breast cancer
recurrence in post-menopausal women with early- stage hormone receptor-positive breast cancer

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Name the 3 aromatase inhibitor drugs

A
  1. Anastrozole
  2. Letrozole
  3. Exemestane
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What are the ADEs of aromatase inhibitors? (7)

A
  1. Hot flashes and flushing
  2. Hypertension
  3. Osteopenia and osteoporosis
  4. Weakness, arthralgia
  5. Fatigue
  6. Less risk for DVT than tamoxifen (≤3%)
  7. Nausea/Vomiting
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Name the GnRH agonist drug

A

Goserelin acetate

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

When/how is goserelin acetate used in adjuvant breast cancer treatment?

A

Used for ovarian function suppression (OFS) for premenopausal women at high risk for a new breast primary (higher risk of recurrence) with hormone receptor positive disease to combine with an aromatase inhibitor rather than tamoxifen alone

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

When/how is goserelin acetate used in metastatic breast cancer treatment?

A

Use as a bridge to oophorectomy in premenopausal women

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What are the symptoms of prostate cancer? (7)

A
  1. Difficulty urinating
  2. Dribbling after finishing urinating
  3. Need to urinate often – especially at night
  4. Pain and blood during urination
  5. Difficulty having or maintaining erection
  6. Unplanned weight loss and appetite
  7. Pain or stiffness in the lower back, hips and pelvis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What are some risk factors for prostate cancer? (4)

A
  1. Older age - 65+
  2. African American higher than Caucasian men
  3. Family history
  4. Obesity
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What are our treatment options for prostate cancer? (5)

A
  1. Watchful waiting – no treatment and physician monitors growth of the cancer with blood tests, rectal exams, biopsies
  2. Radiation Therapy – external beam RT or internal RT also called brachytherapy
  3. Radical prostatectomy – surgery to remove the whole prostate gland
  4. Hormone therapy
  5. Chemotherapy
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

What are the 4 classes of hormonal treatments for prostate cancer?

A
  1. GnRH agonists
  2. GnRH antagonists
  3. CYP17 inhibitor
  4. Antiandrogens
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

Name the GnRH agonists used in prostate cancer (3)

A
  1. Leuprolide acetate (IM injection)
  2. Goserelin acetate (subcutaneous injection)
  3. Relugolix (oral)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

Name the GnRH antagonist used in prostate cancer

A

Degarelix

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

Name the CYP17 inhibitor used in prostate cancer (Need a beer to sip 17 times)

A

Abiraterone

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

Name the Antiandrogens used in prostate cancer (4)

A
  1. Apalutamide
  2. Darolutamide
  3. Enzalutamide
  4. Bicalutamide (oral)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

What is the goal of Androgen Deprivation Therapy (ADT) in prostate cancer treatment?

A

Goal is to reduce serum testosterone to castrate levels – testosterone causes the prostate tumour to grow

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

What is the MOA of GnRH agonist in prostate cancer? (3)

A
  1. Cause down-regulation of hypothalamus-pituitary axis
  2. Initial “flare” response (may be co-prescribed with bicalutamide for initial 14 to 30 days)
  3. Reduce serum testosterone almost as much as bilateral orchiectomy
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

How long are GnRH agonists used for in adjuvant treatment?
How about metastatic setting?

A
  1. Neo-adjuvant/adjuvant = max of 3 years
  2. Metastatic = indefinitely
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

What is the MOA of GnRH antagonist (Degarelix)? (3)

A
  1. Blocks receptors in pituitary decreasing secretion of LH and FSH, resulting in rapid decrease in testosterone production
  2. No initial flare – no need for bicalutamide
  3. Usually reduces testosterone level more rapidly than LHRH agonists
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

What are the ADRs of androgen deprivation? (7)

A
  1. Urinary symptoms 10-15%
  2. Gynecomastia <5%
  3. Hot Flashes (40-80%)
  4. Decreased libido, erectile dysfunction (90-100%)
  5. Fatigue, weight gain, loss of muscle mass
  6. Osteopenia and osteoporosis (3% fracture risk)
  7. Myocardial infarction (0.3%), ↑ QT
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

When is abiraterone used? What is it always combined with?

A
  • Advanced prostate cancer
  • Always combined with prednisone
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

What is the MOA of abiraterone? (CYP17 inhibitor) (3)

A
  1. Blocks androgen production in testes, adrenal glands and tumor
  2. ↓ cortisol production which ↑ACTH leading to an accumulation of mineralocorticoids
    - Hypertension, hypokalemia, edema
  3. Co-administration with prednisone is required to prevent compensatory rise in ACTH
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

Name the androgen receptor blockers (5) (Darol Eatza Apple with his friend Bical, because he has the Flu)

A
  1. Darolutamide
  2. Enzalutamide
  3. Apalutamide
  4. Bicalutamide
  5. Flutamide
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

What is the MOA of androgen receptor blockers?

A

Competitively inhibit androgen binding to receptor

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

MAB naming: -ximab means?

A

Chimeric

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
40
Q

MAB naming: -zumab means?

A

Humanized

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
41
Q

MAB naming: - mumab means?

A

Fully human

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
42
Q

MAB naming - target - ci(r) means?

A

Circulatory system

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
43
Q

MAB naming - target - li(m) means?

A

Immune system

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
44
Q

MAB naming - target - t(u) means?

A

Tumor

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
45
Q

MAB neaming - target - os means?

A

Bone

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
46
Q

Humanized MABs generally contain >__% human sequence
Chimeric MABs generally contain >__% human sequence

A

90
65

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
47
Q

How do MABs work?

A

Work by recognizing and finding specific targeted antigens on cancer cells.
Each MAB recognizes one particular protein. So different MABs have to be made to target different types of cancer. Depending on the protein they are targeting, they work in different way to kill the cancer cell or stop it from growing.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
48
Q

MAB targets are either cell surface antigens or plasma proteins.
What are the big cell surface antigens to know? (3)

A
  1. CD20
  2. EGFR
  3. HER2
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
49
Q

MAB targets are either cell surface antigens or plasma proteins.
What is the big plasma protein to know?

A

VEGF

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
50
Q

The combination of ___________ and ___________ is used in HER2-positive breast cancer, along with a ______

A

pertuzumab; trastuzumab; taxane

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
51
Q

What is a big/most common MAB ADE to be aware of?

A

Infusion reactions

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
52
Q

What are some signs and symptoms of infusion reactions? (7)

A
  1. Fever and/or shaking chills
  2. Flushing and/or itching
  3. Alterations in heart rate and blood pressure
  4. Dyspnea or chest discomfort
  5. Back or abdominal pain
  6. Nausea, vomiting, and/or diarrhea
  7. Various types of skin rashes
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
53
Q

What is a potential fatal ADE of MAB infusions?

A

Cytokine release syndrome

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
54
Q

True or False? Follicular lymphoma treatment is curative

A

False - not curative. Most of these pts will ultimately develop progressive disease

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
55
Q

Should know the anti-CD20 MABs (2)

A
  1. Rituximab
  2. Obinutuzumab
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
56
Q

What is the MOA of anti-CD20 MABs? (3)

A
  1. Antibody-dependent cellular cytotoxicity –‘effector’ immune cells such as natural killer cells and macrophages are recruited to kill the B cells, including the cancerous B cells;
  2. Complement-dependent cytotoxicity – the proteins of the ‘complement’ system are recruited, which damage the B-cell membrane leading to cell death; and
  3. Direct cell death – as rituximab binds to the B cell through the CD20 receptor, the signal causes the B cell to die
57
Q

Rituximab was the first anti-CD20 MAB to be approved for the treatment of?

A

Non-Hodgkin lymphomas

58
Q

What is the bifunctional antibody drug? (Anti-CD19/CD3)

A

Blinatumomab

59
Q

What are 2 EGFR inhibitor MABs to know? (Pani tu masz EGFR in the City)

A
  1. Cetuximab
  2. Panitumumab
60
Q

What is the MOA of cetuximab?

A

Cetuximab inhibition:
When Cetuximab binds to the extracellular domain of the EGFR, it prevents the binding of EGF to the EGFR by physically blocking the ligand binding site on the EGFR. Therefore, it blocks the activation and subsequent dimerization of the receptor, inhibition in signal transduction and anti-proliferative effects. Moreover, this agent may inhibit EGFR-dependent primary tumor growth and metastasis.

61
Q

What is cetuximab (EGFR) indicated for? (2)

A
  1. Approved for locally advanced unresectable or metastatic, non-mutated (wild-type) all RAS (NRAS/KRAS) colorectal cancer as a single agent or in combination with irinotecan
  2. Also combined with radiation as a radio-sensitizer in head and neck cancer squamous cell cancer
62
Q

Should know the name of the VEGF inhibitor used in prostate cancer

A

Bevacizumab

63
Q

What is the MOA of VEGF inhibitors?

A

Binding to all circulating VEGF prevents activation of VEGF receptors

64
Q

What are the indications of bevacizumab? (4)

A
  1. Advanced colorectal
  2. Advanced ovarian and cervical cancers
  3. Recurrent glioblastoma and
  4. In combination with Atezolizumab in advanced liver cancer
65
Q

What are the ADRs of bevacizumab? (4)

A
  1. HTN
  2. Bleeding
  3. Cerebral and myocardial infarction
  4. Proteinuria
66
Q

Name the 2 anti-HER2 breast cancer drugs

A
  1. Trastuzumab
  2. Pertuzumab
67
Q

Trastuzumab blocks HER-2 ____________, Pertuzumab blocks __________________

A

dimerization; heterodimerization

68
Q

Anti-HER2 breast cancer drugs big ADR is?

A

Decrease LVEF

69
Q

What is the MOA of trastuzumab emtansine (T-DM1 –> the DM1 part is chemo)

A

The antibody binds to HER2 on the cell surface and then is internalized. Once internalized, there is a disruption of the linker and the intracellular delivery of the cytotoxic substance (emtansine?) that eventually kills the cancer cell. The goal of treatment in all patients with cancer is to have the chemotherapy only go to those cells that need to be treated and spare normal tissue.

70
Q

Enfortumab vedotin is used in what cancer? (Playing Fornite all day makes me pee myself)

A

Advanced bladder cancer

71
Q

What is the MOA of enfortumab?

A

Antibody drug conjugate (ADC) directed at Nectin-4 (an adhesion protein located on cell surfaces). Nectin-4 is highly expressed in urothelial carcinoma

72
Q

What do epidermal growth factor receptors (EGFRs) do?

A

Regulate cell differentiation, proliferation, and survival

73
Q

There is an important family of four EGFRs to be aware of. What are they?

A

HER1
HER2
HER3
HER4

74
Q

How do tyrosine kinase inhibitors (TKIs) work? (2)

A

1.Tyrosine kinase inhibitors are a family of small molecules or peptides with the ability to inhibit either cytosolic or receptor tyrosine kinases. Inhibition by this class of agents is through direct competition for ATP binding to the tyrosine kinase
2. TKI can compete at the ATP binding site of tyrosine kinase with ATP, reduce tyrosine kinase phosphorylation, thereby inhibiting cancer cell proliferation. It has the characteristics of high selectivity, small adverse reaction and convenient oral administration - patients like the oral convenience.

75
Q

What are growth factors and how do they work? (3)

A
  1. Growth factors are chemicals produced by the body that control cell growth. There are many different types of growth factors and they all work in different ways.
  2. Some growth factors tell cells what type of cells they should become. Some make cells grow and divide into new cells. Some tell cells to stop growing or to die.
  3. Growth factors work by binding to receptors on the cell surface. This sends a signal to the inside of the cell, which sets off a chain of complicated chemical reactions.
76
Q

What are 4 types of growth factors to be aware of and what do they each control?

A
  1. Epidermal Growth Factor (EGF) – controls cell growth
  2. Vascular Endothelial Growth Factor (VEGF) – controls blood vessel development
  3. Platelet Derived Endothelial Growth Factor (PDGF) – controls blood vessel development and cell growth
  4. Fibroblast Growth Factor (FGF) – controls cell growth
77
Q

Compare how MABs work compared to a TKI to inhibit cell signaling

A
  1. MAB - MAbs stop the ligand from binding to RTKs, thus causing no dimerization, no phosphorylation, and no cell signaling. MAbs can bind to ligands or receptors, depending on the type
  2. TKI - TKIs inhibit RTK phosphorylation. The signaling transduction cascade is not started and thus cell signaling and resulting cellular activities do not occur.
78
Q

What are cancer growth blockers? (1+3)

A
  1. A cancer growth blocker is a targeted drug that blocks the growth factors that trigger cancer cells to divide and grow. Scientists are looking at different ways of doing this such as:
    - Lowering levels of the growth factor in the body
    - Blocking the growth factor receptor on the cancer cell
    - Blocking the signals inside the cell that start up when the growth factor triggers the receptor
79
Q

What are 4 types of cancer growth blockers?

A
  1. Tyrosine kinase inhibitors (TKI’s)
  2. Proteasome inhibitors (PIs)
  3. mTOR (mechanistic target of rapamycin) inhibitors
  4. Hedgehog pathway blockers
80
Q

What pharmacological class does this stem belong to: -tinib

A

Tyrosine kinase inhibitor

81
Q

What pharmacological class does this stem belong to: -zomib

A

Proteasome inhibitor

82
Q

What pharmacological class does this stem belong to: -ciclib

A

Cyclin-dependent kinase inhibitor

83
Q

What pharmacological class does this stem belong to: -parib

A

Poly ADP-ribose polymerase inhibitor

84
Q

What pharmacological class does this stem belong to: -iroliumus

A

Mammalian target of rapamycin (mTOR) inhibitor

85
Q

Which drug was the pioneer to targeted therapies (TKI)?

86
Q

All of these drugs belong to what class?
1. axitinib
2. dasatinib
3. erlotinib
4. imatinib
5. nilotinib
6. pazopanib
7. sunitinib
8. erdafitinib

87
Q

What are 4 TKI-EGFR inhibitors used specifically for NSCLC (lung cancer)?
(Drinking Merlot, Getfit? Orfat? Allsummer so FAR (EGFR))

A
  1. Erlotinib
  2. Gefitinib
  3. Afatinib
  4. Osimertinib
    TARGETING EGFR
88
Q

What mutation is osimertinib particularly effective against (lung cancer)?

A

EGFR - T790M mutation
This is the ONLY drug we use for this mutation

89
Q

TKI-ALK inhibitors used in (lung) cancer only work in what scenario?
What is the typical population that has this type of cancer?

A
  1. These drugs only work in cancer cells that have an overactive version of ALK
  2. More common in young patients who are-non smokers
90
Q

What are the TKI-ALK inhibitor drugs used in NSCLC (lung cancer) specifically? (3)
(ALK = ALB - Alect Brigitte for the Lore)

A
  1. Alectinib
  2. Lorlatinib
  3. Brigitinib
91
Q

What are some side effects to be aware of with TKI-ALK inhibitors? (3)

A
  1. ALK inhibition is most commonly associated with GI toxicities.
    - N/V/D
  2. Some laboratory abnormalities such as elevated AST and ALT
  3. Less commonly, pneumonitis.
92
Q

What are 3 TKI-HER2 drugs to be aware of (for breast cancer)?
(Tuco is Nera breast and he wants to Lap HER2)

A
  1. Lapatinib
  2. Neratinib
  3. Tucatinib
93
Q

How do TKI-VEGF inhibitors work? (3)

A
  1. Angiogenesis (VEGF is the master regulator of angiogenesis) is unregulated in many tumors, → tumor growth, invasion and metastasis.
  2. Some drugs stop the VEGF receptors from sending growth signals into the blood vessel cells. These treatments are also called cancer growth blockers or tyrosine kinase inhibitors (TKIs).
  3. Sorafenib (for example) inhibits the action of tyrosine kinase Raf and other factors involved in vasculogenesis (vascular endothelial growth factor receptor and platelet-derived growth factor receptor), which in turn inhibits activation of other downstream multikinases that are normally essential for cell growth, angiogenesis, proliferation and metastasis of HCC cells.
94
Q

TKI-VEGF inhibitors are primarily used in what type of cancer?

95
Q

What are 3 TKI-VEGF inhibitors to know?
(VEGF? Askit a question - Son or Pesos?)

A
  1. Axitinib
  2. Sunitinib
  3. Pazopanib
96
Q

What are some important ADRs of sunitinib and pazopanib (VEGF inhibitors) to be aware of? (3)

A
  1. HFSR
  2. Discoloration of nails or hair
  3. HTN
97
Q

Sorafenib and Regorafenib (VEGF inhibitors) are more so used in what type of cancer?

A

Hepatocellular carcinoma

98
Q

Most people with chronic myelogenous leukemia (CML) have an abnormal chromosome called the?

A

Philadelphia chromosome

99
Q

What is a Philadelphia chromosome?

A
  1. This happens when a gene called the ABL1 gene on chromosome 9 breaks off and sticks to a gene called the BCR gene on chromosome 22 (translocation mutation)
  2. This produces a new gene called BCR-ABL1, known as a fusion gene
100
Q

Imatinib targets what?

A

BCR-ABL (Philadelphia chromosome)
(Has a lot of drug interactions btw)

101
Q

What do RAS-RAF pathways regulate?

A

Normal cell growth and survival

102
Q

Around half of melanomas are caused by a mutation in a gene called ____

103
Q

What is the problem with BRAF inhibitors? (melanoma)

A

Resistance develops quickly

104
Q

The first BRAF inhibitor was called?

A

Vemurafenib

105
Q

Name 3 BRAF inhibitor drugs

A
  1. Vemurafenib
  2. Dabrafenib
  3. Encorafenib
    (BRAF = -fenib)
106
Q

What are BRAF inhibitors combined with for melanoma?

A

MEK inhibitors

107
Q

What is an important counseling tip regarding BRAF inhbitor + MEK inhibitor combo for melanoma?

A

Need to wear sunscreen b/c of phototoxic reactions

108
Q

Name the MEK inhibitors for melanoma (3)
(Franky’s Mech consists of TRAfalgar, Koby, and Bonney)

A
  1. Trametinib
  2. Cobimetinib
  3. Binimetinib
109
Q

Should know the usual BRAF and MEK combinations used for melanoma. There are 3 of them

A
  1. Dabrafenib with trametinib
  2. Vemurafenib with cobimetinib
  3. Encorafenib with binimetinib
110
Q

What even is the point of adding an MEK inhibitor to a BRAF inhibitor? (2)

A
  1. Addition of MEK – inhibitor to BRAF inhibition in melanoma is synergistic and delays onset of drug resistance.
  2. Tolerability is also improved
111
Q

What are proteasomes?

A

Proteasomes are tiny, barrel shaped structures found in all cells. They help break down proteins the cell doesn’t need into smaller parts. The cell can then use them to make new proteins that it does need

112
Q

What is the MOA of proteasome inhibitors (PIs)

A
  1. Treatments that block proteasomes from working are called proteasome inhibitors. They cause a build up of unwanted proteins in the cell, which makes the cancer cells die (induces apoptosis in malignant B cells).
113
Q

What are the 3 proteasome inhibitors to be aware of? What are they used to treat?
(Bort Simpson, give me a Carfil, and pickup Iza, you’ve got Multiple Miles to go ‘ma)

A
  1. Bortezomib (SC)
  2. Carfilzomib (IV)
  3. Ixazomib (PO)
    Treat multiple myeloma
114
Q

What are some ADRs of MEK inhibitors? (4)

A
  1. Fewer cutaneous squamous cell carcinomas
  2. Acneiform rash
  3. Cardiotoxicities
  4. Ocular toxicity
115
Q

What are some ADRs of proteasome inhibitors? (5)

A
  1. Neutropenia
  2. Thrombocytopenia
  3. Peripheral neuropathy
  4. Diarrhea
  5. Hepatitis B or Herpes zoster reactivation
116
Q

Because proteasome inhibitors increase risk for herpes zoster and herpes simplex virus reactivation, what is recommended for patients on a PI?

A

Antiviral prophylaxis is recommended

117
Q

The only thing you need to know about mTOR inhibitors is the name of 1 medication. What is it?

A

Everolimus

118
Q

The only thing you need to know about hedgehog pathway blockers is the name of 1 medication. What is it?

A

Vismodegib

119
Q

JK, another thing to know about hedgehog pathway blockers is who should NOT be on it. So, who is it?

A

Pregnant women because risk of embryofetal death or severe birth defects

120
Q

What is the MOA of PARP inhibitors? (4)

A
  1. Breaks of one DNA strand (single-stranded DNA) can be repaired by the poly-ADP-ribose polymerase (PARP) enzymes, while breaks of both strands (double-stranded DNA; dsDNA) can be repaired by proteins encoded by the breast cancer (BRCA) genes (BRCA1, BRCA2)
  2. If PARP enzymes are inhibited, the cancer cells lose one of the major mechanisms to repair single-stranded DNA breaks, which decreases their viability
  3. Cancer cells with mutated BRCA genes would be less able to repair dsDNA breaks, thus more likely to die. This is because the single-stranded DNA breaks left unrepaired by the PARP inhibition will turn into dsDNA breaks during DNA replication
  4. Inhibitors of PARP can stop the growth of cancer, particularly cancers that have mutated BRCA genes.
121
Q

What is the underlying mechanism by which PARP inhibitors exert their effect? (2)

A
  1. The chromosome contains two long strands of DNA wrapped around each other like a spiral staircase
  2. When one or both DNA strands are damaged (DNA breaks), repair is required in order for DNA replication to proceed and the cell to be viable
122
Q

Know the basic, one sentence MOA of PARP inhibitors

A

By inhibiting PARP, these agents form PARP-DNA complexes, resulting in DNA damage, apoptosis, and cancer cell death

123
Q

PARP inhibitors are used to treat cancers with indications specifically with ____ gene mutations

124
Q

What are 2 PARP inhibitor drugs to know? (Hola, i’m Neara PARK)

A
  1. Niraparib
  2. Olaparib
125
Q

What cancers are PARP inhibitors primarily used in? (3)

A
  1. Ovarian
  2. Breast
  3. Prostate
126
Q

Olaparib is used in breast cancer for how long?

127
Q

The progression through different phases of the cell cycle is controlled by a group of proteins called _______

128
Q

Explain how cancers and CDK4/6 are related?

A

Dysregulation of CDK 4 and CDK 6 allows cancer cells, despite their genetic damage, to progress through the G1 checkpoint to the S phase (DNA synthesis) of the cell cycle

129
Q

CDK4/6 inhibitors are always combined with what?

A

Aromatase inhibitors or tamoxifen

130
Q

What is the basic MOA of CDK4/6 inhibitors?

A

CDK4/6 inhibitors (palbociclib, ribociclib and abemaciclib) prevent the activation of CDK4/6 to cause cell cycle arrest at G1 phase.
Decrease proliferation of tumor cells, induce senscence

131
Q

What are the ADRs of CDK inhibitors? (4)

A
  1. Neutropenia
  2. Stomatitis
  3. Nausea
  4. Fatigue usually mild
132
Q

Name the 3 big CDK4/6 inhibitors (Abe is ma Pal who I like to eat Ribs with)

A
  1. Abemaciclib
  2. Palbociclib
  3. Ribociclib
133
Q

All of the CDK inhibitors can cause ________, but _________ is effective to prevent/treat it

A

alopecia; minoxidil

134
Q

Should know if the following are continuous or cyclic use:
1. Abemaciclib
2. Palbociclib
3. Ribociclib

A
  1. Abemaciclib = continuous
  2. Palbociclib = 3 weeks on 1 week off
  3. Ribociclib = 3 weeks on 1 week off
135
Q

Why are Palbociclib and Ribociclib used cyclically?

A

Because of their risk of neutropenia

136
Q

Ribociclib has two unique ADEs:

A
  1. QT-prolongation
  2. Pneumonitis
137
Q

What is the most common adult leukemia?
What gene is the biggest culprit?

A

Chronic lymphocytic leukemia (CLL)
BCL2 expression

138
Q

What is the only BCL-2 medication to know? (CLL)

A

Venetoclax

139
Q

To mitigate the risk of venetoclax causing TLS (tumor lysis syndrome), what is done?

A

Dose ramp-up period, along with prophylactic hydration and urate lowering therapy.

PHAR 359 (26 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2025 Bold Learning Solutions. Terms and Conditions