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T1 - Phase 2 - Systems Modules (I) > Neoplasia/Hematology - Pharmacology - Chemotherapy; Targeted Therapy; Cancer Immunology > Flashcards

Neoplasia/Hematology - Pharmacology - Chemotherapy; Targeted Therapy; Cancer Immunology Flashcards

1
Q

Describe the mechanism of action of chemotherapeutic alkylating agents:

binding ___ ________ positions in DNA;

causing strand _________;

________-________ing of DNA

A

Describe the mechanism of action of chemotherapeutic alkylating agents:

binding N7 guanosine positions in DNA;

causing strand breakage;

cross-linking of DNA

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2
Q

Name a few examples of alkylating agents:

BCN

CPA

A

Busulfan, cyclosphosphamide, nitrosoureas (carmustine and lomustine);

cisplatin, procarbazine, allopurinol

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3
Q

What type of chemotherapeutic agent is the following?

Busulfan

A

Alkylating agent

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4
Q

What type of chemotherapeutic agent is the following?

Cyclosphosphamide

A

Alkylating agent

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5
Q

What type of chemotherapeutic agent is the following?

Nitrosoureas (carmustine and lomustine)

A

Alkylating agents

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6
Q

What type of chemotherapeutic agent is the following?

Cisplatin

A

Alkylating agent

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7
Q

What type of chemotherapeutic agent is the following?

Procarbazine

A

Alkylating agent

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8
Q

What type of chemotherapeutic agent is the following?

Allopurinol

A

Alkylating agent

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9
Q

What is the major toxic side effect of the chemotherapeutic agent cyclophosphamide?

A

Hemorrhagic cystitis

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10
Q

What are the major toxic side effects of the chemotherapeutic agents procarbazine, cisplatin, and carboplatin?

A

Nephro- and ototoxicity

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11
Q

What are the major toxic side effects of alkylating agents in general?

A

Bone marrow depression

(leukopenia / thrombocytopenia)

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12
Q

What type of chemotherapeutic agent is the following?

Methotrexate

A

Anti-folate

(anti-metabolite)

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13
Q

What type of chemotherapeutic agents are the following?

5-fluorouracil

Cytarabine

A

Anti-pyrimidines

(anti-metabolites)

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14
Q

What type of chemotherapeutic agents are the following?

6-mercaptopurine

6-thioguanine

A

Anti-purines

(anti-metabolites)

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15
Q

What enzyme does methotrexate inhibit in its role as a chemotherapeutic agent?

A

Dihydrofolate reductase

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16
Q

What enzyme does 5-fluorouracil inhibit in its role as a chemotherapeutic agent?

A

Thymidylate synthase

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17
Q

What can be administered to reverse the inhibition of dihydrofolate reductase caused by methotrexate?

A

Leucovorin

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18
Q

What enzyme activates 6-thioguanine and 6-mercaptopurine?

A

HGPRT

(to become purine analogs)

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19
Q

How does cytarabine affect normal cellular function?

A

Its incorporation into DNA induces apoptosis

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20
Q

True/False.

Cytarabine is basically a purine analog.

A

False.

Cytarabine is basically a pyrimidine analog.

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21
Q

True/False.

The triphosphate form of cytarabine is the active form.

A

True.

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22
Q

Gemcitabine is a(n) ___-phase-specific anti-metabolite that enters cells via ______ and ______ transporters.

A

Gemcitabine is a(n) S-phase-specific anti-metabolite that enters cells via CNT and ENT transporters.

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23
Q

True/False.

Anti-metabolites have few negative side effects as chemotherapeutic agents.

A

False.

May cause hair loss, nausea, vomiting, myelosuppression, tumor lysis syndrome;

may cause neurologic, CV, GI, genitourinary, dermatologic, pulmonary, otic, ocular, and hepatobiliary toxicities;

may cause dysethesias, toxic epidermal necrolysis, and Stevens-Johnson syndrome;

etc.

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24
Q

Describe the mechanism of action of taxanes (e.g. paclitaxel and docetaxel) as chemotherapeutic agents.

A

Microtubule stabilization

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25
Q

Describe the mechanism of action of vinca alkaloids (e.g. vincristine and vinblastine) as chemotherapeutic agents.

A

Inhibition of microtubule formation

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26
Q

Describe the mechanism of action of anthracyclines and etoposides as chemotherapeutic agents.

A

Topoisomerase inhibition

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27
Q

Vinca alkaloids (e.g. vincristine, vinblastine) and taxanes (e.g. paclitaxel, docetaxel) mainly act at which phases of the cell cycle?

A

M phase

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28
Q

Name a few toxic side effects of paclitaxel.

A

Neutropenia, thrombocytopenia;

peripheral neuropathy

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29
Q

Name the main toxic side effect of vincristine.

Name the main toxic side effect of vinblastine.

A

Marrow depression;

peripheral neuritis

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30
Q

What is a common toxicity of vincristine and vinblastine (remember chemo man)?

A

Peripheral neuropathy (Chemo man’s V-shaped arms and legs)

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31
Q

What are two common toxicities of cisplatin (remember Chemo Man)?

A

Ototoxicity and kidney toxicity (both shaped like C’s on Chemo Man)

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32
Q

What is a common toxicity of bleomycin (remember Chemo Man)?

A

Pulmonary fibrosis (lungs look like B’s on Chemo Man)

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33
Q

What is a common toxicity of cyclophosphamide (remember Chemo Man)? How is it prevented?

A

Hemorrhagic cystitis (bicycle in half-pipe of Chemo Man); mesna

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38
Q

What is a common toxicity of adriamycin (doxorubicin) and daunorubicin (remember Chemo Man)?

A

irreversible, dose-dependent cardiotoxicity (heart failure)

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39
Q

Name a medication that blocks topoisomerase II.

Name two medications that block topoisomerase I.

A

Etoposide — (two supercoils at a time);

iratecan, topotecan — (one​ supercoil at a time)

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40
Q

Doxorubicin is an example of what type of chemotherapeutic agent?

A

An anthracycline

(a type of toposiomerase II inhibitor)

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41
Q

True/False.

Much of the cardiotoxicity caused by anthracyclines such as doxorubicin is due to oxidative reactions that damage DNA and mitochondrial membranes.

A

True.

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42
Q

Etoposide and teniposide are _________ alkaloids that block topoisomerase II and have a main toxic side effect of ______________ic toxicity.

A

Etoposide and teniposide are plant alkaloids that block topoisomerase II and have a main toxic side effect of hematolymphatic toxicity.

43
Q

Bleomycin is an ____________ that can exert a chemotherapeutic effect by formation of _________ _________.

A

Bleomycin is an antibiotic that can exert a chemotherapeutic effect by formation of free radicals.

44
Q

What is the main toxic effect of bleomycin?

A

Pulmonary fibrosis

45
Q

Name two antibiotics commonly used as chemotherapeutic agents.

A

Bleomycin;

dactinomycin

46
Q

___________ therapy encompasses all treatments that are administered before the primary cancer treatment, whereas ___________ therapy describes regimens administered after the primary treatment.

A

Neoadjuvant therapy encompasses all treatments that are administered before the primary cancer treatment, whereas adjuvant therapy describes regimens administered after the primary treatment.

47
Q

Adjuvant therapy encompasses all treatments that are administered ________ the primary cancer treatment, whereas neoadjuvant therapy describes regimens administered ________ the primary treatment.

A

Adjuvant therapy encompasses all treatments that are administered after the primary cancer treatment, whereas neoadjuvanttherapy describes regimens administered before the primary treatment.

48
Q

Which form of chemotherapy in addition to primary treatment has an increased likelihood of detecting micrometastases before they are clinically apparent?

(Adjuvant or neoadjuvant chemotherapy)

A

Neoadjuvant therapy

49
Q

Which form of chemotherapy in addition to primary treatment has an decreased likelihood of resulting in overadministration of unnecessary treatment?

(Adjuvant or neoadjuvant chemotherapy)

A

Adjuvant chemotherapy

50
Q

Fill in the blanks for the stages of drug testing:

  1. Does it _________
  2. Is it ________
  3. Is it ________
  4. Can it ________ in ________
A

Fill in the blanks for the stages of drug testing:

  1. Does it work?
  2. Is it safe?
  3. Is it better?
  4. Can it stay in market?
51
Q

True/False.

Alkylating agents can lead to secondary leukemias.

A

True.

52
Q

Tamoxifen can lead to what negative side effects?

A

Menopausal symptoms;

endometrial carcinoma;

thrombosis

53
Q

Name two targeted therapies that specifically inhibit estrogen receptors at the breast.

A

Tamoxifen;

raloxifen

(also, tormifen)

54
Q

True/False.

Tamoxifen and raloxifen are aromatase inhibitors that are largely cytotoxic.

A

False.

Tamoxifen and raloxifen are breast estrogen receptor inhibitors that are largely cytostatic.

55
Q

True/False.

Although tamoxifen increases risk of thrombosis, it decreases the risk of damaging cardiovascular events.

A

True.

56
Q

Name the medication most commonly used to modulate the estrogen receptor.

Name the medication most commonly used to modulate the HER-2/Neu receptor.

A

Tamoxifen;

trastuzumab

57
Q

Name a few third-generation aromatase inhibitors.

A

Anastrozole;

letrozole;

exemestane

58
Q

Name a steroidal antiestrogen medication that has a higher affinity for the estrogen receptor than tamoxifen.

A

Fulvestrant

59
Q

Do progestins typically have strong antiestrogenic or antiandrogenic effects?

A

Both!

60
Q

What medication is used for androgen antagonism at the level of the prostate?

A

Flutamide

(also bicalutamide, nilutamide)

61
Q

Name the original medication synthesized to treat CML by blocking BCR-ABL tyrosine kinase.

A

Imatinib (Gleevec)

62
Q

Name the main medication used to block the EGFR.

A

Gefitinib

(only effective in tumor cells with mutated or overexpressed EGFRs)

63
Q

Name the mechanism of action of the following medications:

Palbociclib

Abemaciclib

Ribociclib

A

Cyclin D kinase 4/6 inhibition

64
Q

_________ is a dual tyrosine kinase inhibitor that interrupts the HER-2/neu and epidermal growth factor receptor (EGFR) pathways.

A

Lapatinib is a dual tyrosine kinase inhibitor that interrupts the HER-2/neu and epidermal growth factor receptor (EGFR) pathways.

65
Q

__________ is a nitrogen-containing bisphosphonate used to prevent bone loss and treat osteoporosis.

A

Pamidronate is a nitrogen-containing bisphosphonate used to prevent bone loss and treat osteoporosis.

66
Q

Give an example of an mTor inhibitor sometimes used in cancer therapy.

A

Everolimus

67
Q

Cancer therapies that block PARP have what effect on tumor cells?

A

Inability to correct DNA damage

68
Q

Which BRCA mutation carries a higher risk of breast cancer development?

A

BRCA1 (55 - 65%)

69
Q

What medication is often given prophylactically to prevent breast cancer development in high-risk women?

A

Tamoxifen

70
Q

What medication is associated with DVT and endometrial carcinoma?

A

Tamoxifen

71
Q

What medication type is better for post-menopausal women who need adjuvant or primary therapy for breast cancer?

A

Aromatase inhibitors

72
Q

All women who have PR+ or ER+ breast cancer should be treated with anti-_________ therapy.

A

All women who have PR+ or ER+ breast cancer should be treated with anti-estrogen therapy.

73
Q

What is the first line of natural defense against tumorigenesis?

A

DNA repair

74
Q

What cell types provide some surveillance in watching out for cancer cells?

A

NK cells;

macrophages

75
Q

What in particular do macrophages secrete upon finding a tumor cell?

A

TNF

76
Q

Where are most natural killer cells in the body?

A

The bloodstream

77
Q

Macrophages need to be ______activated in order to kill tumor cells.

A

Macrophages need to be hyperactivate in order to kill tumor cells.

78
Q

What is the name for the PD-1 receptor?

A

Programmed cell Death protein 1

79
Q

In normal, healthy tissues, PD-1 interaction with PD-L1 blocks what?

A

Autoimmunity

(downplays leukocyte activity)

80
Q

Healthy tissues express what to inhibit leukocyte activity and prevent autoimmunity?

A

PD-L1

81
Q

Many tumor cells up-regulate PD-___ to evade immune responses by binding PD-___ on leukocyte surfaces.

A

Many tumor cells up-regulate PD-L1 to evade immune responses by binding PD-1 on leukocyte surfaces.

82
Q

Why do abnormal proteins expressed on tumor cell MHC (class I) not typically induce an immune response?

A

Lack of co-stimulation

(T cells that bind the MHCs without co-stimulation become anergic)

83
Q

Name two receptors found on leukocytes that inhibit immune actiivty when bound,

A

PD-1

CTLA-4

84
Q

Name a few of the ways that monoclonal antibodies can be used to modulate tumor cell activity:

Blocking _________ (e.g. trastuzumab);

inducing _________ (e.g. rituximab);

blocking _________ _________ proteins (e.g. nivolumab blocking PD-1);

conjugation of antibody to _________ or _________

A

Name a few of the ways that monoclonal antibodies can be used to modulate tumor cell activity:

Blocking receptors (e.g. trastuzumab);

inducing apoptosis (e.g. rituximab);

blocking immune regulatory proteins (e.g. nivolumab blocking PD-1);

conjugation of antibody to radioisotopes or toxins

85
Q

Name a few examples of PD-1/PD-L1 inhibitors used in cancer therapy:

_______umab (PD-1)

_______umab (PD-1)

Atezolizumab (PD-L1)

Durvalumab (PD-L1)

A

Pembrolizumab (PD-1)

Nivolumab (PD-1)

Atezolizumab (PD-L1)

Durvalumab (PD-L1)

86
Q

Name a few examples of PD-1/PD-L1 inhibitors used in cancer therapy:

Pembrolizumab (PD-1)

Nivolumab (PD-1)

_______umab (PD-L1)

_______umab (PD-L1)

A

Pembrolizumab (PD-1)

Nivolumab (PD-1)

Atezolizumab (PD-L1)

Durvalumab (PD-L1)

87
Q

Name a few toxicities seen in up to ~20% of cases of PD-1/PD-L1 administration.

A

Pneumonitis;

colitis

(also endocrinopathy)

88
Q

Name an example of a CTLA-4 inhibitor.

A

Ipilimumab

89
Q

True/False.

Use of inhibitors of PD-1, PD-L1, or CTLA-4 in cancer therapy are all associated with inflammation of any organ system.

A

True.

90
Q

What does the term ‘CAR-T cell’ stand for?

A

Chimeric antigen receptor - T cells

91
Q

CAR-T cell therapy has been FDA approved for treatment of what disease(s)?

A

B-ALL;

diffuse large B cell lymphoma

(both must be CD19+)

92
Q

True/False.

CAR-T cell therapy currently seems to be very effective, but it is also very expensive and associated with severe toxicities.

A

True.

(up to 80% response rates;

$750,000 per treatment;

cytopenias + neurotoxicities + cytokine release syndromes)

93
Q

True/False.

CAR-T cell therapy is basically an allograft of T cells that have a high affinity for the specific tumor cells found in the patient (modified in the lab to have this high affinity).

A

False.

CAR-T cell therapy is basically an autograft of T cells that have a high affinity for the specific tumor cells found in the patient (modified in the lab to have this high affinity).

94
Q

Cytokine release syndrome is a syndrome of massive inflammation mediated by IL-___ that leads to ______-like symptoms.

A

Cytokine release syndrome is a syndrome of massive inflammation mediated by IL-6 that leads to shock-like symptoms.

95
Q

What monoclonal antibody is anti-IL-6 and can be used to treat cytokine release syndrome?

A

Tocilizumab

96
Q

What are bispecific T cell engagers (BiTEs)?

A

A monoclonal antibody that connects T cells to tumor cells.

97
Q

Give an example of a monoclonal antibody that acts as a bispecific T cell engager (BiTE).

A

Blinotumomab

T1 - Phase 2 - Systems Modules (I) (27 decks)

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