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Fall 2024 > PHRM 868 (Therapeutics IV) Exam 1 > Flashcards

PHRM 868 (Therapeutics IV) Exam 1 Flashcards

1
Q

The majority of cancers are found where?

A

In the sex organs

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2
Q

Cancer occurs more in which population?

A

Older people

(age 65-74) (median age=67)

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3
Q

Why do older people develop more cancers?

A

People accumulate more genetic mutations as they age

(from more cell divisions and more exposures to toxic substances)

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4
Q

True or False: Cancer mortality is decreasing

A

True

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5
Q

Which cancer has had a massive increase in cases within recent years, making it the most common cancer?

A

Lung cancer

-due to the large increase in cigarette smoking in the 60’s

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6
Q

What is a neoplasm?

A

“New growth”

-May be benign or malignant
(can be cancerous or non-cancerous)

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7
Q

What is a tumor?

A

A nonspecific term to describe a lump or swelling

(can be cancerous or non-cancerous)

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8
Q

What is cancer?

A

Any malignant neoplasm (new growth)

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9
Q

What is hyperplasia?

A

An increase in organ or tissue size due to an INCREASE IN THE NUMBER OF CELLS

-can be physiologic, compensatory, or pathologic

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10
Q

What is metaplasia?

A

An adaptive, SUBSTITUTION of one type of adult tissue to another type of adult tissue

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11
Q

What is dysplasia?

A

An abnormal cellular proliferation in which there is LOSS OF NORMAL ARCHITECTURE

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12
Q

What is anaplasia?

A

A LOSS OF STRUCTURAL DIFFERENTIATION
(cells start to look the same)

-Cells dedifferentiate
-Frequently occurs in tumors

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13
Q

True or False: Normal epithelial cells are very organized

A

True

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14
Q

What is the site where lung cancer occurs?

A

Bronchial epithelium

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15
Q

What is a carcinoma?

A

Malignant neoplasm (new growth) of SQUAMOUS EPITHELIAL CELL origin

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16
Q

What is a papilloma?

A

A benign carcinoma

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17
Q

What is an adenocarcinoma?

A

Malignant neoplasm derived from GLANDULAR TISSUE

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18
Q

What is an adenoma?

A

A benign adenocarcinoma

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19
Q

What is a sarcoma?

A

Malignant neoplasm originating in MESENCHYMAL TISSUES or its derivatives

(ex: bone, muscle, fat)

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20
Q

Where is mesenchymal tissue found?

A

Bone, Muscle, Fat

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21
Q

What are lymphoma and leukemia?

A

Malignant neoplasms of hematopoietic tissues

(blood cells/ plasma)

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22
Q

What is melanoma?

A

Cancer of pigment producing cells

(ex: melanocytes in the skin or eye [uveal Melanoma])

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23
Q

What is blastoma?

A

Malignancies in precursor cells (AKA blasts)
-more common in children

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24
Q

What is a teratoma?

A

A germ cell neoplasm made of several different differentiated cell/tissue types

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25
Q

Leukemia is a cancer of which cells?

A

White blood cells of hematopoietic origin

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26
Q

Stage 0 in the Numerical Staging System of Carcinomas means what?

A

In situ carcinoma
*No sign of local invasion

-Has not gone outside of the tissue it is originally diagnosed in

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27
Q

Stage I in the Numerical Staging System of Carcinomas means what?

A

Microscopic invasion of surrounding tissue

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28
Q

Stage II in the Numerical Staging System of Carcinomas means what?

A

4-9 surrounding lymph nodes are involved

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29
Q

Stage III in the Numerical Staging System of Carcinomas means what?

A

10 or more surrounding lymph nodes are involved

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30
Q

The Numerical Staging System of Carcinomas is largely based on what 3 factors?

A

-Tumor Size
-Tumor Location
-Tumor Number

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31
Q

Stage IV in the Numerical Staging System of Carcinomas means what?

A

Distant metastases are detected

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32
Q

Primarily only which tumors get staged through the numerical staging system?

A

Solid tumors

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33
Q

True or False: Stage 4 cancer always means lethality

A

False

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34
Q

In the TNM staging system, what do T, N, and M stand for?

A

T: Primary Tumor
N: Regional Lymph Nodes
M: Distant Metastasis

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35
Q

What does “X” mean in the TNM staging system?

A

Cannot be evaluated

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36
Q

What does “0” mean in the TNM staging system?

A

No evidence/ No involvement

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37
Q

What does a Tis stage in the TNM staging system mean?

A

Carcinoma In Situ (CIS)

-abnormal cells are present but have not spread to neighboring tissue
-although not cancer, CIS may become cancer and is sometimes called preinvasive cancer

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38
Q

What does T1, T2, T3, T4 mean in the TNM staging system?

A

Represents the size and/or extent of invasion of the primary tumor

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39
Q

What does N1, N2, N3 represent in the TNM staging system?

A

Degree of regional lymph node involvement
(number and location of lymph nodes)

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40
Q

What does M1 in the TNM staging system mean?

A

Distant metastasis is present

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41
Q

Summary Staging includes what 5 main categories?

A

In Situ
Localized
Regional
Distant
Unknown

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42
Q

What is the In Situ Stage of summary staging?

A

Abnormal cells are present only in the layer of cells in which they developed

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43
Q

What is the Localized Stage of summary staging?

A

Cancer is limited to the organ in which it began, without evidence of spread

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44
Q

What is the Regional Stage of summary staging?

A

Cancer has spread beyond the primary site to nearby lymph nodes or tissues and organs

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45
Q

What is the Distant Stage of summary staging?

A

Cancer has spread from the primary site to distant tissues or organs or to distant lymph nodes

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46
Q

What is the Unknown Stage of summary staging?

A

There is not enough information to determine the stage

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47
Q

What is a tumor grade?

A

The description of a tumor assigned by a pathologist

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48
Q

What is a “well-differentiated” tumor?

A

The cells of the tumor and the organization of its tissue resemble those of normal cells and tissue

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49
Q

What is an “undifferentiated” or “poorly differentiated” tumor?

A

A tumor with abnormal-looking cells and which may lack normal tissue structures

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50
Q

True or False: “well-differentiated” tumors tend to grow and spread at slower rates than “undifferentiated/ poorly differentiated” tumors

A

True

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51
Q

What does a grade of GX mean?

A

Grade cannot be assessed (undetermined grade)

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52
Q

What does a grade of G1 mean?

A

Well differentiated (low grade)

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53
Q

What does a grade of G2 mean?

A

Moderately differentiated (intermediate grade)

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54
Q

What does a grade of G3 mean?

A

Poorly differentiated (high grade)

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55
Q

What does a grade of G4 mean?

A

Undifferentiated (high grade)

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56
Q

What are the 3 characteristics of cancer?

A

-Uncontrolled Cellular Growth
-Tissue Invasion
-Metastasis

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57
Q

Which characteristic of cancer is also a characteristic of benign tumors?

A

Uncontrolled cellular growth

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58
Q

True or False: For many tumors the growth of the primary tumor is not going to be life threatening

A

True

-Can become deadly when it moves out of these areas

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59
Q

What is RSV

A

Retrovirus
(integrates into the genome)

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60
Q

RSV encodes what oncogene?

A

v-Src

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61
Q

The oncogene v-Src is similar to which protein in the body?

A

Src

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62
Q

What was the first discovered example of an oncogene?

A

v-Src

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63
Q

What is a proto-oncogene?

A

Any gene in a healthy cell capable of promoting tumor growth

(not necessarily going to turn cancerous)

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64
Q

What is Alfred Knudsen’s 2-hit hypothesis?

A

For any tumor to develop, you need two mutations in a tumor suppressor gene for it to not work and to be able to develop a tumor (both alleles must be mutated). If you have one mutation you would only need one more, therefore you are more likely to develop the tumor. People with no mutations are less likely since they must develop two

-Heterozygous mutations can be inherited and families show increased susceptibility to cancers

(most tumor suppressors can be expressed from either chromosome which is why they need homozygous deletion/mutation to stop working)

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65
Q

What is retinoblastoma?

A

A childhood retinal cancer in which retinal cells do not stop dividing during development and form tumors

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66
Q

What is RB1?

A

Tumor suppressor

*this is the tumor suppressor gene affected in retinoblastoma

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67
Q

What is p16?

A

Tumor suppressor

-prevents moles from becoming cancerous

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68
Q

True or False: Carcinogen-induced cancers have lower mutation rates

A

FALSE

carcinogen-induced cancers have very high mutation rates

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69
Q

What are the two most common carcinogens that induce cancer?

A

Smoking

UV exposure

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70
Q

Mutations in the EGFR catalytic domain have what effect?

A

Increase the intensity and duration of signaling in response to ligand

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71
Q

What is “synthetic lethality”?

A

Loss of function mutations in tumor suppressor genes can predict susceptibility to chemotherapies

(if a normal cell has two genes, by targeting one the cell will still survive because the second gene is still active. If a tumor cell has already lost function of one gene, we can target the other and kill the tumor cell without killing the healthy cells)

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72
Q

What are BRCA1 and BRCA2?

A

Tumor suppressor genes

-encode for proteins involved in DNA repair

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73
Q

The nonfunctional mutant alleles of BRCA 1/2 are inherited as what?

A

Germline mutations

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74
Q

BRCA mutations in breast cancer increase susceptibility to what?

A

PARP inhibitors

(PARP repairs double-stranded DNA breaks, Base-excision repair)

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75
Q

Both PARP1 and BRCA are responsible for what?

A

DNA repair

PARP1= Base-excision repair
BRCA= Homologous Recombination

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76
Q

When both PARP1 and BRCA are blocked, what happens?

A

DNA cannot repair itself, cell dies

*this is why PARP inhibitors are useful in cancer cells that already have non-functioning BRCA genes

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77
Q

What kind of drug is Olaparib?

A

PARP inhibitor

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78
Q

What cancers is Olaparib used to treat?

A

Cancers with BRCA 1/2 mutations

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79
Q

What is the MOA of Olaparib?

A

Traps PARP to DNA
–is unable to uncouple from DNA and unable to repair strand breaks

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80
Q

What is the current 5-year cancer survival rate overall?

A

69%

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81
Q

True or False: No cancers are currently curable by chemotherapy

A

False, but only a small number are

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82
Q

What are the 2 defining features of chemotherapies?

A

Non-specific

Toxic to cells

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83
Q

What is the Central Dogma of Biology

A

DNA (replicates) -> Transcription -> RNA -> Translation -> Protein

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84
Q

What happens in G0 of the cell cycle?

A

No division

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85
Q

What happens in G1 of the cell cycle?

A

Cell is quiescent or accumulating “building blocks” required for division

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86
Q

What happens in S of the cell cycle?

A

Cell replicates DNA

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87
Q

What happens in G2 of the cell cycle?

A

Cell assembles machinery for chromosomal segregation and cytokinesis

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88
Q

What happens in M of the cell cycle?

A

Mitosis

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89
Q

The cell cycle is controlled by what?

A

Cyclins paired with cyclin-dependent kinases

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90
Q

What is the R point?

A

The restriction point, this is the critical time point when cells decide whether or not to enter the cell cycle

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91
Q

What are cell cycle checkpoints?

A

Decision points where cells decide to proceed through the cell cycle

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92
Q

The G1 to S checkpoint in the cell cycle checks for what?

A

Do you have what you need to be able to double DNA?

(ensures the integrity of the genome)

-Is there a mitogenic signal telling the cell to proceed through the cell cycle?
-Are there sufficient quantities of the required nucleotide “building blocks”?
-Is there unrepaired DNA damage?

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93
Q

The S to G2 checkpoint in the cell cycle checks for what?

A

-Has the genome been replicated?
-Are there any errors (that have been made in doubling the DNA)?

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94
Q

The G2 to M checkpoint in the cell cycle checks for what?

A

-Have sister chromatid arms been separated?

-Has the machinery required for chromosomal segregation and cytokinesis been assembled?

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95
Q

Proteins that drive the cell cycle can act as what?

A

Oncogenes

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96
Q

Proteins that halt the cell cycle can act as what?

A

Tumor suppressors

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97
Q

What is P53?*

A

Tumor suppressor

“guardian of the genome”

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98
Q

What checkpoint does P53 affect?

A

G2

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99
Q

What is the function of RAS or KRAS?*

A

Give a strong signal to divide

(common oncogenic mutation)

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100
Q

What checkpoint does RAS or KRAS affect?

A

G0

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101
Q

What is RB1?*

A

Tumor suppressor

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102
Q

What is P16?

A

Tumor suppressor

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103
Q

What are the 2 master regulators of cell cycle initiation?

A

Cyclin D

CDK 4,6

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104
Q

What are mitogens?

A

Things that promote growth

(include estrogens, tyrosine kinases, etc)

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105
Q

What is the function of CDK 4/6?

A

-Master regulator of cell cycle initiation

-Phosphorylates RB1 (tumor suppressor) causing it to no longer work, this increases cell division

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106
Q

What kind of drug is Palbociclib?

A

CDK 4/6 kinase inhibitor

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107
Q

Is Palbociclib a targeted therapy?

A

No -targets all replicating cells

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108
Q

What cancers is Palbociclib approved to treat?

A

Cancers arising due to BRCA 1/2 mutations

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109
Q

Why are common chemotherapies selective for cancer cells?

A

-Tumor cells have lost cell cycle control mechanisms
(have increased cell proliferation)
(checkpoint controls are often lost as well!)

*Cancer cells do not fully repair damaged DNA, repair damaged mitotic spindles, or finish replicating DNA before proceeding to the next stage of the cell cycle

Opportunity: loss of checkpoint control results in increased cell death with chemotherapy

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110
Q

What happens to the cell cycle in cancer cells treated with chemotherapy that have lost G1/S checkpoint control?

A

-Cells do not halt in G1 and attempt to replicate damaged DNA

-This can trigger apoptosis

-If the cell has lost its apoptotic response, the cell replicates the damaged DNA and acquires lethal genetic damage that results in necrosis (cell death resulting in lysis and inflammation)

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111
Q

DNA alkylating agents are able to target cells in which stage of the cell cycle?

A

DO NOT REQUIRE CELLS TO BE CYCLING

-Are effective against cancer cells resting in G0 AND cells progressing through the cell cycle

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112
Q

What are some examples of cell cycle non-specific drug classes?

A

-Alkylating agents

-DNA intercalation agents

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113
Q

What does it mean for a drug to be cell cycle non-specific?

A

-They are most effective when the tumor cells are progressing through the cell cycle
-These drugs are not dependent upon the cell being in a specific phase of the cell cycle
-Many of these agents have some efficacy against cells resting in G0, but are more effective against cells progressing through the cell cycle

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114
Q

What does it mean for a drug to be phase-specific (or schedule-dependent)?

A

-They are most effective against tumor cells in a specific phase of the cell cycle
-They affect cellular events that occur within a specific phase of the cell cycle (ex: DNA synthesis, mitosis)

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115
Q

What is a limitation associated with phase-specific (or schedule-dependent) drugs?

A

The number of cells killed is limited to the number of cells present in the appropriate phase of the cell cycle

Higher doses of the drug may not result in greater tumor cell killing

Increased cell killing requires prolonged drug exposure

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116
Q

What are the major dose-limiting toxicities associated with chemotherapies?

A

Hematopoietic: WBC (granulocytes)- infections, Platelets- hemostasis, RBC- anemia

Gastrointestinal: Nausea & vomiting, loss of appetite

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117
Q

Cancer chemotherapy kills a constant ____, not a constant _______, of tumor cells

A

Cancer chemotherapy kills a constant fraction, not a constant number, of tumor cells

(it is impossible to kill all tumor cells with a single dose of drug, it will select for cells resistant to drug)

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118
Q

What is the Norton-Simon hypothesis for chemotherapy?

A

Give as dose-intensive and as early as possible
-Give chemotherapy at shorter intervals
-Use combination drugs with distinct mechanism of action

Why:
-Chemotherapy selects for cells resistant to the drug
-As tumor cells grow, their doubling time slows (remember most anticancer agents work on cycling cells)
-When the tumor burden decreases, the remaining cells re-enter exponential growth
-Diminishing returns: resistant and/or intolerable side effects

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119
Q

What factors increase the success rates of chemotherapies?

A

-Small tumor size
-Early diagnosis
-Increased drug intensity

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120
Q

True or False: Individual drugs in combination should be used at maximal doses

A

True

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121
Q

What is a commonly used combination of drugs in combination chemotherapy?

A

CHOP

-Cyclophosphamide (alkylating agent)
-Doxorubicin (anthracycline)
-Vincristine (microtubule inhibitor)
-Prednisone (steroid)

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122
Q

What are the advantages of combination chemotherapy?

A

-No additive toxicity for drugs with non-overlapping toxicities

-Increased cell killing

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123
Q

What are the possible ways that tumors initially sensitive to chemotherapy can become resistant?

A

-Altered drug metabolism
-Changes in drug target or function
-Physiological changes that promote resistance

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124
Q

What are the ways that tumors can alter drug metabolism to become resistant to chemotherapy?

A

-Increased transport of drugs out of the cell through efflux pumps
-Reduced transport into the cell
-Decreased activation of prodrug
-Increased detoxification of drug molecule
-Cell survival mechanisms

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125
Q

How can changes in drug target or function lead to tumors becoming resistant to chemotherapy?

A

-Increased expression of drug target through gene amplification or expression (upregulation of target makes it harder to inhibit)
-Emergence of mutant, structurally altered target (mutants are still active but do not bind the drug)
-Emergence of cells bearing alterations in genes whose products are functionally redundant with the drug target (cells can rewire pathways to bypass the need for the drug target)

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126
Q

What physiological changes can occur to tumors that make them more resistant to chemotherapy?

A

-Refuge of cancer cells in drug-protected anatomical sites (ex: metastasis to the brain where drugs do not cross the blood-brain barrier)

-Massive stromalization (structure impedes drug transport)

-Changes in cell state such as EMT (epithelial mesenchymal transition) (slows cell cycle, increases drug efflux pumps and increases anti-apoptotic proteins)

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127
Q

What cell survival mechanisms may allow a tumor to become resistant to chemotherapy?

A

-Activation of anti-apoptotic regulators (prevent cell death)
-Increased repair of damage caused by chemotherapies (most commonly the repair of drug-DNA adducts or DNA damage)

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128
Q

True or False: Chemotherapy is a narrow therapeutic index drug

A

True

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129
Q

What are the roles of glucocorticoids in cancer treatment?

A

-Have anti-cancer effects in the treatment of blood cancers
-Used as palliative care to: reduce inflammation, edema, and manage pain during chemotherapy
-Reduce hypersensitivity reactions, nausea, vomiting, and immune-related adverse effects

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130
Q

What are the 3 commonly used glucocorticoids?

A

Methylprednisolone
Prednisolone
Dexamethasone

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131
Q

What are the roles of hormonal therapies in cancer treatment?

A

*Disease specific- only for hormone-dependent cancers

(ex: breast, prostate, endometrial cancer)

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132
Q

Hormonal therapies target what?

A

Estradiol (breast, endometrial) and Dihydrotestosterone (prostate)

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133
Q

Where are the hormones targeted by hormonal therapies produced?

A

Adrenal glands
Ovary
Testis
Adipocytes

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134
Q

True or False: Hormonal cancers are considered more treatable cancers

A

True
-because we can target these cancers

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135
Q

What are the 2 strategies for endocrine therapy?

A
  1. Stop steroid receptor function
  2. Decrease production of steroids
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136
Q

Where is Gonadotropin-Releasing Hormone (GnRH) produced?

A

Hypothalamus

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137
Q

Where is LH/FSH produced?

A

Anterior pituitary gland

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138
Q

If a patient has measurable estrogen receptors (ER) or progesterone receptors (PR) in their tumor, what does this mean for their prognosis?

A

It is a better prognosis because these receptors can be targeted
(high correlation between the presence of estrogen receptors and the likelihood of response to hormone therapy)
(Even stronger for ER+/PR+ tumors)

139
Q

Which tumors are more likely to have estrogen receptors (ER+): poorly differentiated or well differentiated tumors?

A

Well differentiated tumors

-poorly differentiated tumors have higher growth fractions and are generally more sensitive to cytotoxic agents (chemotherapy)

140
Q

True or False: Hormone therapy in breast cancer is generally limited to ER+/PR+ tumors

A

True

141
Q

P450scc changes cholesterol to what?

A

Pregnenolone

142
Q

Which enzyme creates dehydroepiandrosterone?

A

17, 20 lyase

143
Q

Which enzyme converts testosterone to dihydrotestosterone?

A

5a-reductase

144
Q

Which enzyme converts Androstenedione to Estrone and Testosterone to Estradiol?

A

Aromatase (CYP19)

(converts androgens to estrogens)

145
Q

What is the first line treatment for ER+ tumors?

A

Endocrine therapy

146
Q

What range of ER positivity is usually considered for endocrine therapy?

A

10%

(ER status can be heterogeneous)

147
Q

Breast cancer is made up of 4 distinct diseases, what are they?

A

Luminal A/B
HER2-enriched
Basal-like
Claudin-low

148
Q

ER+ tumors typically fall into which disease of breast cancer?

A

Luminal A/B

149
Q

HER2 amplicon normally fall into which disease of breast cancer?

A

HER2-enriched

150
Q

BRCA1 mutations normally fall into which disease of breast cancer?

A

Basal-like

151
Q

Triple Negative Cancers (no estrogen, progesterone, or HER2) typically fall into which disease of breast cancer?

A

Claudin-low

152
Q

Triple Negative Cancers (no estrogen, progesterone, or HER2) are typically treated with what?

A

Cytotoxic therapy (chemotherapy)

153
Q

What common ending do the SERMs have?

A

“fene”

154
Q

What are the 4 SERMs? (selective estrogen modulators)

A

Tamoxifen
Toremifene
Clomiphene
Raloxifene

155
Q

What common ending do the SERDs have?

A

“trant”

156
Q

What 2 drugs are SERDa?

A

Fulvestrant
Elacestrant

157
Q

What kind of drug is Tamoxifen?

A

SERM

158
Q

True or False: Tamoxifen is a prodrug

A

True

159
Q

What must Tamoxifen be metabolized to in order for it to work? (must be metabolized to non-prodrug state)

A

4-OH-TAM

160
Q

Which enzyme is responsible for the conversion of Tamoxifen to the high-affinity metabolite 4-OH-TAM?

A

CYP2D6

161
Q

How does being a CYP2D6 poor metabolizer affect Tamoxifen use?

A

Do not recommend Tamoxifen for these patients because they will be metabolized to a much less powerful form and the drug will not be as strong

162
Q

Tamoxifen binding to estrogen receptors will affect what?

A

Translocation

DNA binding

*in a tissue-specific manner

163
Q

Tamoxifen has both antagonist and agonist effects, what are its antagonist effects on estrogen?**

A

-Blocks estrogen-dependent breast cancer cell proliferation
-Hot flashes (due to anti-estrogen effects)

164
Q

Tamoxifen has both antagonist and agonist effects, what are its agonist effects on estrogen?

A

-Increased incidence of endometrial cancer
-Preserved bone density in postmenopausal women

165
Q

Can Tamoxifen be used in premenopausal, postmenopausal, or both women?

A

Both!

166
Q

What tumors are Tamoxifen primarily used to treat?

A

ER+/PR+ breast cancer

*Also metastatic ER+/PR+ breast cancer

First drug approved for breast cancer prevention in high-risk patients***

167
Q

What is a benefit to using the SERM Raloxifene over Tamoxifen?

A

No endometrial hyperplasia

168
Q

What kind of drugs are Fulvestrant and Elacestrant?

A

SERDs (Selective Estrogen Receptor Down-modulator)

169
Q

Do Fulvestrant and Elacestrant act as antagonists or agonists?

A

Antagonists

(no agonist effects)
(full antagonist at high doses)

170
Q

Which SERD is taken po and which is taken IM?

A

Fulvestrant= IM

Elecestrant= PO

171
Q

What are SERDs approved to treat?

A

ER+ metastatic breast cancer in postmenopausal women who have progressed on other antiestrogen therapy

172
Q

Can SERDs treat premenopausal, postmenopausal, or both women?

A

Postmenopausal only

173
Q

What cells act as a source of estrogen in postmenopausal women?

A

Adipocytes

174
Q

Aromatase inhibitors that block the conversion of androgens to estrogens target what?

A

Peripheral tissue (adipose tissue)

NOT THE OVARY

175
Q

What is the primary application of aromatase inhibitors and who is this used in?

A

Application: Estradiol suppression in postmenopausal women

176
Q

What are the 2 imidazole-based non-steroidal aromatase inhibitors?

A

Anastrozole
Letrozole

177
Q

What is the MOA of Letrozole and Anastrozole?

A

Potent and selective COMPETITIVE inhibitors of aromatase activity

178
Q

Are Letrozole and Anastrozole used in premenopausal, postmenopausal, or both women?

A

Postmenopausal

179
Q

What are Letrozole and Anastrozole used to treat?

A

Breast cancer

-either first line or can be started after 3-5 years of tamoxifen

*Note that these drugs show increased bone density loss compared to tamoxifen

180
Q

What is the steroidal aromatase inhibitor drug?

A

Exemestane

181
Q

Exemestane is structurally related to what?

A

Androstenedione (“suicide inhibitor”)

182
Q

What is the MOA of the steroidal aromatase inhibitor Exemestane?

A

Acts as a false substrate that aromatase converts to a reactive intermediate

This intermediate binds irreversibly at the active site and inactivates the enzyme

183
Q

What is the indication for Exemestane?

A

Treats estrogen-responsive breast cancer in postmenopausal women who have progressed on antiestrogen therapy

184
Q

Is Exemestane used in premenopausal, postmenopausal, or both women?

A

Postmenopausal women only

185
Q

LH activates which enzyme?

A

Chol-SCC

*this converts cholesterol to progesterone to corticosteroids

186
Q

FSH activates which enzyme?

A

Aromatase (CYP19)

187
Q

How do the Gonadotropin Releasing Hormone analogs work? (GnRH analogs)

A

They are peptide analogs of the neurohormone GnRH with modified amino acids to increase potency and reduce degradation

Create chronic stimulation of the GnRH receptors in the pituitary which eventually shuts them off leading to decreased aromatase and decreased estrogen

*Get a “flare” for 2-3 weeks at the beginning where estrogen increases before shutting off (originally increases tumor size)

Available in a depot formulation suitable for slow-release

188
Q

What are the GnRH analogs?

A

Leuprolide acetate
Goserelin

189
Q

What are the side effects of Leuprolide acetate and Goserelin?

A

-Transient worsening of symptoms due to initial increase in estrogen

Long term:
-Hot flashes
-Sexual dysfunction

*side effects are typical of antiestrogenic effects (menopausal)

190
Q

Are GnRH analogs used in premenopausal, postmenopausal, or both women?

A

PREMENOPAUSAL

191
Q

What is the indication for Leuprolide acetate and Goserelin?

A

Premenopausal breast cancer

192
Q

What are the treatment options for premenopausal women with breast cancer?

A

GnRH agonists
Tamoxifen (SERM)
Surgical oophorectomy

193
Q

What are the treatment options for postmenopausal women with ER+ breast cancer?

A

Tamoxifen (SERM)
Nonsteroidal aromatase inhibitors
Steroidal aromatase inhibitors
Pure anti-estrogens (SERDs)

194
Q

What is the Gleason Score used for in prostate cancer and what does a higher or lower score mean?

A

Used to stage prostate cancer based on how well differentiated or undifferentiated the cancer is

Lower number= Well differentiated (1)

Higher number= Poorly differentiated/More cancer cells (5)

195
Q

*Which enzyme is responsible for the conversion of testosterone to dihydrotestosterone (DHT)?

A

Type II 5-a reductase

196
Q

Where does dihydrotestosterone bind in prostate cells?

A

Androgen Receptor (AR)

*note: this binding results in translocation to the nucleus and activates genes that drive cell growth

197
Q

Where is the androgen receptor (AR) located?

A

Cytoplasm

198
Q

How can prostate cancer affect the androgen receptor (AR)?

A

AR can be amplified in prostate cancer

199
Q

What range of Prostate Specific Antigen (PSA) indicates prostate cancer?

A

> 6.5 ng/ml

200
Q

Besides breast cancer, what other indication do the GnRH analogs Leuprolide acetate and Goselerin have?

A

-Palliative treatment of advanced prostate cancer
-Chemical castration within 3-4 weeks

201
Q

What are the side effects of GnRH analogs (Leoprolide acetate and Goselerin) in men?

A

Gynecomastia
Decreased sexual dysfunction

*Get a flare of symptoms at start of treatment

202
Q

What are the GnRH antagonists used in prostate cancer?

A

Degarelix
Relugolix

203
Q

What are the GnRH antagonists (Degarelix and Relugolix) used for?

A

Advanced prostate cancer with need for androgen deprivation therapy

204
Q

What is a benefit to using GnRH antagonists (Degarelix and Relugolix)?

A

Will not cause a flare of testosterone production like the analogs do

205
Q

What is the main goal of treatments for prostate cancer?

A

To stop the production of dihydrotestosterone (DHT)

206
Q

Which drug functions as a steroid analog?

A

Abiraterone

207
Q

What is the MOA of Abiraterone?

A

Inhibits the function of 17 a-hydroxylase and C17,20 lyase

(CYP17 catalyzes the conversion of pregnenolone and progesterone to DHEA and androstenedione)

208
Q

What is a common side effect of Abiraterone?

A

Increased cholesterol levels

209
Q

What are the mechanisms of resistance to endocrine therapy seen in prostate cancer?

A

-Mutations in androgen receptors (AR) can result in androgen independent activation and prevent binding of AR antagonists

(referred to as Castration Resistant Prostate Cancer (CRPC))

210
Q

What affect does signal transduction through kinases have on cancer?

A

Drives cancer proliferation

*kinases= mitogenic signaling (tell cells that they should divide)
*we want to target kinases with kinase inhibitors

211
Q

What is the substrate that ALL kinases use?

A

ATP

212
Q

What gets tested via PCR from lung biopsies to determine if a patient has a particular mutation of EGFR?

A

Genomic DNA

*if positive, these patients go on anti-EGFR therapies

213
Q

Cell signaling is largely driven by what?

A

The transfer of phosphates

(ATP is the major source of the phosphate group that will be transferred by a kinase to a target protein)

214
Q

What are the common targets for phosphorylation by kinases?

A

*Tyrosine
Serine, Threonine, Lipids

(nucleophilic substances)

215
Q

What do phosphatases do?

A

Have the opposite action of kinases

*Remove phosphorylation

Note: cancers often show deletion of phosphatases

216
Q

What is included in the general structure of a kinase?

A

N- and C- lobes connected by a hinge region

Activation loop that controls access to the active site

217
Q

How many types of reversible kinase inhibitors are there?

A

3

218
Q

What is a Type I kinase inhibitor?

A

Binds to the active conformation of the kinase

219
Q

What is a Type II kinase inhibitor?

A

Binds to and stabilizes the inactive conformation of the kinase

220
Q

What is a Type III kinase inhibitor?

A

Occupy an allosteric pocket outside of the ATP-binding pocket

(is the only one that does not bind to the ATP-binding pocket)

221
Q

How do competitive kinase inhibitors work?

A

They bind the kinase in a reversible fashion and must compete with ATP for binding

222
Q

How do covalent kinase inhibitors work?

A

They bind covalently with a reactive nucleophilic cysteine residue proximal to the ATP-binding site

-this results in blockage of the ATP site and irreversible inhibition

223
Q

What patients will likely respond well to EGFR inhibitors?

A

Those with mutations in EGFR that cause it to be constitutively activated

224
Q

How does EGFR affect cancer?

A

-Functions through tyrosine kinase
-EGFR signaling induces cell proliferation
-EGFR is over expressed and has higher signaling activity in many cancers
-Overexpression of EGFR correlates with a poor prognosis

225
Q

What is the MOA of Gefitinib/ Erlotinib?

A

Small molecule reversible inhibitors of EGFR tyrosine kinase

-Competitively inhibit the enzyme by binding to the ATP binding site in the kinase domain
-Inhibition of the kinase activity turns off the signal to proliferate

226
Q

What are Gefitinib/Erlotinib used to treat?

A

Patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have EGFR exon 19 or 21 mutations

227
Q

What is Afatinib?

A

Covalent inhibitor of all ErbB receptors

228
Q

What does Afatinib treat?

A

EGFR mutant non-small cell lung cancer (NSCLC) with EGFR mutations

Therascreen Kit has been approved for detection of EGFR exon 19 deletions or exon 21 (L858R) substitution mutations

229
Q

Mutations in what can cause resistance to Geftinib?

A

T790M

230
Q

When a T790M mutation occurs, and Gefitinib can no longer be given to treat NSCLC, what drug can be used in its place and act like a new “key” to fit this change?

A

Osimertinib

231
Q

What is Osimertinib?

A

3rd generation EGFR inhibitor

Covalent kinase inhibitor

Effective against the T790M mutant EGFR that makes Gefitinib no longer work

232
Q

What are the two ErbB molecules?

A

EGFR (ErbB1)

HER2 (ErbB2)

233
Q

How is HER2 affected in breast cancer?

A

Genomically amplified in breast cancer

-Forms hetero/homo dimers that activate signal transduction without a ligand binding
*note: forms a heterodimer with EGFR

234
Q

What is the normal function of HER2?

A

Growth Factor

-sends signals to cells telling them to grow and divide (Same as EGFR)

235
Q

What is Lapatinib?

A

Small molecule, reversible, tyrosine kinase inhibitor that blocks both HER2 and EGFR signaling

(these molecules often work together so this is good)

236
Q

What is Lapatinib used to treat?

A

HER2+ breast cancer

Combination with capecitabine: Treatment of advanced metastatic breast cancer in patients who have progressed on other therapies

237
Q

What is the action of Tucatinib?

A

Small molecule tyrosine kinase inhibitor

*Preferentially binds HER2

238
Q

What is Tucatinib used to treat?

A

HER2+ breast cancer

239
Q

What is a benefit of using Tucatinib over Lapatinib?

A

Reduced adverse reactions

(potentially due to increased HER2 specificity)

240
Q

What mutation is common in acute myeloid leukemia?

A

FLT3 mutations

either an internal tandem duplication (ITD, more common) or an activating mutation in the tyrosine kinase domain (less common)

*These mutations lead to increased proliferation and decreased apoptosis

241
Q

What is FLT3?

A

A ligand that is a cytokine receptor important for hematopoietic cell survival and proliferation

242
Q

What is Midostaurin?

A

First generation FLT3 inhibitor
(broad kinase inhibitor)

-Used to treat FLT3 mutations in Acute Myeloid Leukemia

243
Q

What is Crenolanib?

A

Second generation FLT3 inhibitor

(more specific)

-Used to treat FLT3 mutations in Acute Myeloid Leukemia

244
Q

What is Quizartinib?

A

Type II FLT3 inhibitor

**Specifically used for internal tandem duplication (ITD) mutations of FLT3 in Acute Myeloid Leukemia

245
Q

What critical part of tumor formation is VEGFR involved in?

A

Angiogenesis

(and it drives tumor cell growth)

*important possible target

246
Q

What is the Philadelphia chromosome (Ph1) and how does it contribute to cancer formation?

A

Part of one protein is combined (translocated) with part of another protein (“Frankenstein protein”), this leads to cancer

The 5’-portion of the Bcr gene combines with the 3’-portuon of the Abl gene

A chimeric transcript is produced called Bcr-Abl

247
Q

What % of chronic myeloid leukemia is the Philadelphia chromosome (Ph1) found in?

A

95%

248
Q

How does Bcr-Abl cause cancer?

A

It is a chimeric protein that is constitutively active

*note that Abl is a tyrosine kinase

249
Q

What is Imatinib?

A

Type II small molecule inhibitor of the Abl tyrosine kinase

250
Q

What is the result of inhibiting the Abl tyrosine kinase?

A

Reduced proliferation

Enhanced apoptotic cell death

251
Q

What is Imatinib used to treat?

A

Chronic Myeloid Leukemia (CML)

252
Q

Which type of medication must patients be on for life?

A

Abl inhibitors

*note that resistance is a lifelong battle

253
Q

What is Ponantinib?

A

BCR-Abl inhibitor

-Effective against all major mutant forms of BCR-Abl

254
Q

What mutation is considered the “gatekeeper” mutation and is resistant to all but one BCR-Abl compound?

A

T315I

255
Q

What drug can be used to inhibit the T315I mutation?

A

Ponatinib

256
Q

What role does the EML4-ALK translocation play in cancer?

A

Wild type ALK is a transmembrane receptor tyrosine kinase similar to EGFR

When ALK and EML4 inappropriately fuse, it becomes cytoplasmic and constitutively active

*Occurs in non-small cell lung cancers

257
Q

What is Dabrafenib?

A

Second generation BRAF-V600 inhibitor

257
Q

What is Alectinib?

A

Specific inhibitor of ALK

258
Q

What is Alectinib indicated to treat?

A

Patients with anaplastic lymphoma kinase (ALK+) metastatic non-small cell lung cancer (NSCLC) who have progressed on or are intolerant to crizotinib

259
Q

What drug is Dabrafenib commonly used in combination with and what do they treat?

A

Used in combination with Trametinib to treat BRAF V600E/K mutant metastatic melanoma

*combination seems to stem induction of squamous cell carcinomas by activated wild type BRAF

*Also used for NSCLC that have BRAF-600 mutations

260
Q

What type of cancer with Ras and GRAF-V600 mutations does not tend to respond o Dabrafenib?

A

Colorectal cancer

261
Q

What is Trametinib?

A

Type III allosteric inhibitor (first approved)

Inhibits the kinase activity of MEK1 and MEK2

262
Q

What is a limitation to the use of Trametinib?

A

Not indicated for treatment of patients who have received prior BRAF inhibitor therapy

263
Q

What is the most common side effect of Trametinib?

A

Rash

264
Q

How does Acalabrutinib work?

A

Covalent BTK inhibitor

-Also targets Cys481

*More potent and selective than 1st generation ibrutinib

265
Q

What is Acalabrutinib indicated for?

A

B-cell lymphoma

266
Q

What is Sirolimus?

A

Inhibits the function of mTOR (a serine-threonine kinase)

267
Q

What is the role of Sirolimus in cancer treatment?

A

Inhibits the immune response by blocking IL-2 signal transduction

(immunosuppressant -such as with organ transplants)

268
Q

True or False: Kinase inhibitors cure patients

A

FALSE

-resistance is a major problem with these medications

-keep a patient in remission and the hope is they will die of something else before the cancer comes back

269
Q

How do antimetabolites work?

A

Mimic the natural cellular substrates/cofactors (metabolites) that enzymes act on (they are analogs)

*Most of these are enzyme inhibitors

Block production of nucleotide building blocks required for DNA replication and transcription
-Target intermediary metabolic pathways involved in synthesis of essential molecules in proliferating cells

*Most require biotransformation to nucleotide analog (sugar and phosphate) to generate active species

270
Q

Which part of the cell cycle do antimetabolites target?

A

S

(DNA replication)

271
Q

*What is the most common dose-limiting side effect of drugs that are toxic to rapidly proliferating cells?

A

Myelosuppression

272
Q
A
273
Q

What is a nucleobase?

A

Just a single base

274
Q

What is a nucleoside?

A

Base + Sugar

275
Q

What is a nucleotide?

A

Base + Sugar + Phosphate

276
Q

Most antimetabolites are nucleobases or nucleosides even through many enzymes use nucleotides. Why is this?

A

The phosphate group on the nucleotide cannot go through cell membranes

Therefore, antimetabolites are normally nucleobases or nucleosides that get converted to nucleotides inside of the cell

277
Q

Which two nucleobases are purines (big molecules)?

A

Adenine
Guanine

278
Q

What are the 2 functions of pyrimidine analogs?

A

-Interfere with pyrimidine nucleotide synthesis
(5-FU + Capecitabine)

-Inhibit DNA polymerase
(Ara-C + Gemcitabine)

*note: can also incorporate into DNA and RNA and interfere with function and replication

279
Q

What is the primary function of uridine analogs?

A

Inhibit thymidine synthesis from uracil

(blocking this step causes you to have no thymidine and ultimately no DNA)

280
Q

What kind of drug is 5-Fluorouracil (5-FU)?

A

Fluorinated uracil analog

-Uridine analogs inhibit thymidine synthesis from uracil

281
Q

What active species is 5-Fluorouracil (5-FU) converted to?

A

Fluorodeoxyuridine monophosphate (Fdump)

*note: this is a nucleotide

282
Q

How is thymidine normally synthesized?

A

When folates are present:
-Thymidylate synthase synthesizes thymidine monophosphate (TMP) from deoxy uridine monophosphate (dUMP)

-The hydrogen on dUMP gets replaced with a methyl on TMP

*Note: folate acts as a methyl donor
*Note: this mechanism is dependent on being able to pull a hydrogen off of dUMP and exchange it with a methyl to make TMP
*Note: Urine gets converted to thymine

283
Q

How does FdUMP inhibit thymidine synthesis?

A

-Fdump mimics dUMP
-Binds the active site of thymidylate synthase
-The hydrogen is replaced with a Fluorine and cannot be pulled off to replace with a methyl
-The reaction cannot go to completion and thymidylate synthase is trapped
-TMP cannot be produced and DNA synthesis is inhibited “thymineless death”

284
Q

How can toxicity with FdUMP be overcome?

A

Use thymidine treatment as rescue therapy

(because FdUMP depletes thymine levels)

285
Q

What kind of inhibitor is FdUMP?

A

Covalent

286
Q

What genetic variability makes some patients more susceptible to toxicity with use of 5-Fluorouracil (5-FU)?

A

Deficiency of the enzyme dihydropyrimidine dehydrogenase (DPD) which breaks down 5-FU

287
Q

What drug has synergy with 5-Fluorouracil (5-FU)?

A

Leucovorate

(folate cofactor converted to tetrahydrofolate in cells)

(more tetrahydrofolate means that there is more covalent ternary complex with thymidylate synthase for the drug to bind)

288
Q

What is the main function of cytosine analogs?

A

Inhibit DNA synthesis

289
Q

What active species is Cytarabine converted to and how does it work?

A

Ara-CTP

-competitive inhibitor of DNA polymerase a

290
Q

What genetic variability can lead to toxicity of Cytarabine?

A

Cytidine deaminase converts cytarabine to non-toxic uracil arabinoside

*Decreased levels of cytidine deaminase in the CNS increase toxicity in the brain and spinal cord

291
Q

Which molecule has synergy with Cytarabine?

A

Tetrahydrouridine

-acts as a cytidine deaminase (CDA) inhibitor, preventing drug conversion to a non-toxic form

292
Q

What is the main function of purine analogs?

A

Inhibit purine biosynthesis

293
Q

What is 6-Mercaptopurine?

A

Purine analog

(adenine analog)

294
Q

What is the function of 6-Mercaptopurine?

A

Inhibits multiple enzymes in de novo purine biosynthesis

blocks synthesis of purine nucleotides

295
Q

Loss of function of which molecule can lead to 6-Mercaptopurine toxicity?

A

Thiopurine methyl transferase (TPMT)

(this molecule inactivates 6-MP)

296
Q

What drug does 6-mercaptopurine interact with and what is the interaction?

A

Allopurinol

-Drug used to treat gout
-Xanthine oxidase is the enzyme that breaks down 6-MP
-Allopurinol is a xanthine oxidase inhibitor
-Leads to toxicity of 6-MP, cannot take these drugs together

297
Q

What is the role of folate?

A

-Essential vitamin (B9)
-Used in synthesis of thymidine from uridine
-Acts as a methyl donor
-Reduced to tetrahydrofolate by dihydrofolate reductase (DHFR)
-DHFR inhibition inhibits thymidine monophosphate (TMP) synthesis

298
Q

How does Methotrexate work?

A

Folate analog

-binds and inhibits DHFR to inhibit thymidine monophosphate synthesis

-this inhibits RNA and protein synthesis + purine and pyrimidine synthesis

299
Q

What medication can be used to rescue from a methotrexate overdose?

A

Leucovorin

(serves as folate)

300
Q

What are the 2 roles of Leucovorin?

A

Increases effects of 5-FU

Rescue for Methotrexate toxicity

301
Q

What is the basic function of alkylating agents?

A

Generate electrophilic (electron deficient) intermediates that react with nucleophilic (electron rich) groups on DNA and proteins

-Attach alkyl group to DNA and protein

-Alkylate purine bases in DNA

302
Q

What is the most common site of alkylation in purines by alkylating agents?

A

Guanine N7

303
Q

What were the earliest alkylating agents?

A

Mustard Gas

304
Q

What are alkylating agents used to treat?

A

Leukemia and Lymphoma

(because they kill off the immune system)

305
Q

What are the effects of DNA alkylation?

A

Intrastrand linking between two bases on the same strand

Interstrand cross-linking of two separate strands

*these effect the double helix shape of DNA and cause it to no longer be recognized by enzymes for replication/transcription

306
Q

What molecule in the body acts as a good nucleophile and can therefore cause resistance to alkylating agents by quenching their activity?

A

Glutathione

307
Q

What are the side effects associated with alkylators?

A

-Mutagenic: cause lots of DNA damage and may form other cancers (second malignancies)
-Target rapidly dividing cells
-Myelosuppression
-Nausea
-Vomiting
-Carcinogenic
-Teratogenic

308
Q

What is Chlorambucil?

A

Alkylating agent with additional aryl group to decrease the nucleophilicity of the nitrogen
(stabilized)

309
Q

What is Cyclophosphamide?

A

Alkylating agent that is a prodrug and requires hydrozylation

310
Q

What enzyme hydroxylates Cyclophosphamide?

A

CYP P450

311
Q

What enzyme inactivates Cyclophosphamide?

A

Aldehyde dehydrogenase

*note: there are higher levels of this present in the bone marrow which results in lower toxicity here and less myelosuppression overall

312
Q

What harmful substance is produced from the activating hydroxylation reaction of Cyclophosphamide?

A

Acrolein

313
Q

What harmful reaction can acrolein cause?

A

Hemorrhagic cystitis

-toxic to bladder mucosa

314
Q

What substance is administered to counteract acrolein in the bladder?

A

Mesna

(accumulates in the urine)
-free thiol (nucleophile) on mesna reacts with and inactivates the acrolein metabolites (electrophile)

-adding a charged group to the acrolein prevents it from going into cells

315
Q

What is Mitomycin C?

A

Alkylating agent
(aziridine-containing natural product)

*can form bifunctional adducts (crosslinks)

316
Q

What are platinum drugs?

A

Covalent crosslinkers that do not alkylate (do not have alkyl groups)

317
Q

What is cisplatin?

A

Platinum drug, the original prototype

318
Q

What are the resistance mechanisms to alkylators and platinum compounds?

A

-Increased intracellular concentration of non-protein thiols, especially glutathione
(react with electrophilic drugs)

-Increased expression of cellular glutathione S-transferase (GST)

319
Q

What is the function of topoisomerases?

A

-Provide a mechanism to reduce localized supercoiling
-Provide access to double stranded DNA by enzymes responsible for replication, transcription, and repair

320
Q

What is the function of Type 1 Topoisomerases?

A

Cut one strand of double stranded DNA
-relax the remaining strand and reanneal

321
Q

How do Topoisomerase I inhibitors work?

A

Covalently bind Top1 ad blocks the re-ligation of DNA from happening

*Top 1 is not just inhibited, it is stuck onto DNA covalently

-Results in inactive Top 1, broken DNA, and a glob stuck to DNA (DNA cannot function)

322
Q

Cells in what phase are most sensitive to Topo 1 cleavage?

A

S

323
Q

What are Topotecan and Irinotecan?

A

Topoisomerase 1 inhibitors

-semisynthetic analogs of natural product camptothecin

324
Q

Which Topoisomerase 1 inhibitor is a prodrug?

A

Irinotecan

325
Q

Before being prescribed Irinotecan, patients must be genetically tested for what?

A

Low expression of UGT1A1
-this can lead to increased toxicity

326
Q

What is the function of Topoisomerase II ?

A

Relieves torsional strain and untangles DNA

-by catalyzing double-stranded DNA breaks

327
Q

How do Topoisomerase II inhibitors work?

A

Bind TOP after it has broken DNA and prevent the re-ligation of DNA

This causes the double-stranded breaks in the DNA to be stuck

Topoisomerase II is stuck covalently to DNA

328
Q

Which topoisomerase inhibitors are considered chemotherapies?

A

ONLY those that produce double-stranded DNA breaks

329
Q

What is Doxorubicin?

A

Topoisomerase 2 inhibitor

330
Q

Which drug is used to prevent patients from developing cardiotoxicity associated with free radicals formed with Doxorubicin?

A

Dexrazoxane

331
Q

What is Etoposide?

A

Topoisomerase 2 inhibitor

*blocks religation of double stranded breaks but does not intercalate

332
Q

What is Bleomycin?

A

Glycopeptide antibiotic

333
Q

What is dynamic instability?

A

Proteins build up microtubules (polymerization) until they get to a point where they just fall apart

-Growing and shrinking of microtubules happens on its own

334
Q

What are the 2 requirements for the spindle assembly checkpoint?

A

Kinetochores need to be attached to the spindle microtubules

Needs to be kinetochore tension (need kinetochores to be attached to both sides so they can pull the sister chromatids apart)

335
Q

What is a Vinca Alkaloid?

A

Prevent microtubule assembly

(cannot build the microtubule)

336
Q

What is a Taxane?

A

Prevent microtubule disassembly

(stabilize the microtubule, cannot pull chromosomes apart, cannot search for chromosomes, eventually run out of tubulin monomers)

337
Q

What was the first immunotherapy?

A

Coley’s toxin

338
Q

What is the function of B cells?

A

Produce antibodies

339
Q

If the stem of all monoclonal antibodies is -mab, what are the 4 possible substems?

A

-o = mouse
-xi = chimeric
-zu= humanized
-u = fully human

340
Q

What was the CLEOPATRA trial?

A

Clinical
Evaluation
Of
Pertuzumab
And
Trastuzumab

341
Q

What is the function of CD20?

A

-Regulates an early step in the activation of the cell cycle and differentiation

-Works with B-cell receptor to drive proliferation of B-cells

-Role in proliferation of B-cell lymphoma

-Binding to this with antibodies induces antibody-dependent cytotoxicity

342
Q

What cells express CD20?

A

Normal B lymphocytes

Immature pre-B cells

B-cell non-Hodgkins lymphoma cells

Fall 2024 (16 decks)

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