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PHAR 123* > Cancers > Flashcards

Cancers Flashcards

1
Q

What are the lab tests for the diagnosis of cancer?

A

Complete blood count
Blood protein staining
Tumor marker tests
Circulating tumor cell (CTC) tests - uncommon

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2
Q

Explain the complete blood count test

A

Counts the number of different types of cells in the blood
Abnormality in number and morphology: possibility of blood cancer (leukemia, lymphoma, myeloma)
Use a bone marrow biopsy to confirm a blood cancer

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3
Q

Explain the RBC test

A

RBC count, hemoglobin (carrying prot for O2 and CO2), hematocrit (volume of blood that consist of RBC) and reticulocyte count (immature RBCs)

Use a bone marrow biopsy to confirm a blood cancer

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4
Q

Explain the WBC test

A

WBC number and differential of the groups of WBC
Monocytes, lymphocytes, neutrophils, basophils, eosinophils
- They all show up at different times during cancer
Look for abnormal numbers and shapes, and confirm with a bone marrow biopsy

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5
Q

What is the platelet (PLT) test?

A

Platelet count, mean platelet volume (avg size of platelets), and platelet distribution width (platelet uniformity)

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6
Q

Explain blood protein staining. How is it performed? What does it determine? Which cancers can it detect?

A

Serum electrophoresis
Test protein abnormality and loss of proteins
Aids in the diagnosis of lymphoma, chronic lymphocytic leukemia and multiple myeloma

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7
Q

What are the electrophoretic zones of blood protein staining?

A

Albumin (transports many molecules and drug molecules)
alpha-1 antitrypsin
alpha-2 macroglobulin
beta-1 and beta-2 transferrin (some myeloma and leuk)
gamma globulin (some myeloma and lymphoma)

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8
Q

What is the cancer type, sample, and purpose of the following markers: CA-125, CD25, EGFR gene mutation, Estrogen receptor.

A

CA-125: Ovarian cancer, blood, diagnosis and treatment
CD25 (surface protein): Non-Hodgkin lymphoma, blood, targeted therapy
EGFR gene mutation: Non-small cell lung cancer, tumor, treatment and prognosis (this one has a lower survival rate, no diagnosis purpose)
Estrogen receptor: Breast cancer, tumor, hormone therapy and targeted therapy

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9
Q

What is seen in CA-125 and ovarian cancer?

A

Cancer antigen 125 is a glycoprotein with a molecular weight greater than 200 kD
It is tested by immunoassay
Normal range in the blood is less than 46 U/mL
Cancer patients have higher than normal ranges due to ovarian cancer

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10
Q

What can be said about high CA-125 numbers?

A

The higher the number the more likelihood to be advanced stage cancer and prognosis

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11
Q

Ture or False: Ovarian cancer is the only reason for high CA-125 levels in the blood

A

False, can also be caused by other diseases that can increase levels (but not as much as cancer)

Examples include:
Endometriosis, liver disease, menstruation, pregnancy, uterine fibroids

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12
Q

What is the use of 70-gene signature and what stages of breast cancer are involved? What does it test?

A

Predicts metastasis and recurrence of breast cancer
It aids in early-stage breast cancer tx (stage 1 and 2)

It tests the activity of 70 different genes in the breast cancer tissue (<3 infected lymph nodes)
(cancer is defined by many proteins, not just one)

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13
Q

Explain the three liquid biopsy tests approved by the FDA

A

CTC test for breast, colorectal, and prostate cancer

Ferrofluid nanoparticle-based technology

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14
Q

What are the types of cancer diagnostic imaging?

A

Breast mammogram, CT scan, PET scan, MRI imaging

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15
Q

Explain the breast mammogram

A

Low dose x-ray imaging
Two images of each breast taken at approx 0.4 millisilverts
It shows abnormal areas in the breast based on images
Used for screening of breast cancer

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16
Q

Explain CT, PET, and MRI

A

Computerized Tomography (CT) = X-ray scan from different angles and computer-processed cross-sectional images

Positron Emission Tomography (PET) = use a radioactive drug as a tracer. Ex) fluorodeoxyglucose

Magnetic Resonance Imaging (MRI): uses magnetism, radio waves, and a computer to produce images (avoid wearing metal jewelry)

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17
Q

What is the main way to diagnose most types of cancer? Explain and provide examples

A

Cancer biopsy = Remove a piece of tissue from a pt’s body and analyze it in a lab
Biopsy analysis: confirmation of cancer, cancer grade (differentiated = low grade; undifferentiated = high grade), targets for targeted therapy

ex) bone marrow biopsy, endoscopic biopsy, needle biopsy, skin biopsy, surgical biopsy

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18
Q

What is the major therapy for cancer?

A

Surgery

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19
Q

Explain surgery for cancer tx

A

Remove the entire tumor (esp. early phase). It is to ease cancer sx that cause pain and pressure

Debulk a tumor = remove some but all of a tumor because entire tumor removal might damage organ. When removing a tumor we need to remove extra, healthy tissue to reduce the residual cancer cells (ex. breast tissue + surrounding fatty tissue).

Smaller residual tumor volume may be associated with longer survival for cancer patients

Breast cancer 2cm vs 20cm: smaller one has pt living two years longer

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20
Q

What are the types of surgery? Explain each

A

Open surgery -> cut open (usually done in early stages)
Minimally invasive surgery -> thru tiny incisions, non-robotic and robotic surgery
Cryosurgery -> use liquid nitrogen to tx skin cancers and retinoblastoma
Laser surgery -> on surface tumors on body, laser beam it
Hyperthermia -> radiofrequency ablation

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21
Q

Explain the da Vinci XI robotic surgery system

A

Dr uses the remote control unit, while the robotic armed unit is with the patient allowing the surgeon to be able to perform surgeries overseas

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22
Q

What isradiation therapy?

A

Apply high doses of radiation to kill cancer cells and reduce tumor size

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23
Q

Whats the purpose of radiation therapy?

A

Treatment and palliative care

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24
Q

What types of radiation therapy do we have available to us?

A

External and internal radiation therapy beam

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25
Q

Explain radiation therapy beam

A

photons - protons and electrons
3D conformal radiation therapy
Intensity-modulated radiotherapy

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26
Q

What is 3D conformal radiation therapy?

A

Allows doctors to direct radiation beams to conform the shape of the tumor.
CT scan is used to provide the 3D dimension of the tumor and nearby organs
Beams are arranged to avoid normal organs and target the tumor

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27
Q

What is 3D conformal radiation therapy?

A

Allows doctors to direct radiation beams to conform the shape of the tumor.
CT scan is used to provide the 3D dimension of the tumor and nearby organs
Beams are arranged to avoid normal organs and target the tumorWhat

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28
Q

What is intensity modulatedd radiotherapy?

A

CT scan can be used to provide the 3D dimension of the tumor and nearby organs.
Multiple beams are positioned for the therapy.
Each beam is divided into small beams

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29
Q

When do we use intensity modulated radiotherapy?

A

Used for hard to treat areas

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30
Q

What is brachy therapy?

A

a sealed container of radioactive material into the therapy

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31
Q

What is radioisotope therapy?

A

Reduce the size of the tumor such as I-131 for thyroid cancer

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32
Q

What is radioimmuno therapy?

A

Combination of radioisotopes and monoclonal antibodies

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33
Q

What is radioembolization?

A

Radioactive beads along with emobolization ( reduced blood to an organ)

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34
Q

True or false.
Chemotherapy is used alone or in combination with other therpais

A

True

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35
Q

What is adjuvent chemotherapy?

A

Often used after primary treatments sucha as surgery or radiotherapy
destroy micro-metastasis
prevent or reduce cancer reccuring

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36
Q

What is neoadjuvent chemotherapy?

A

Given before the main treatment such as surgery or radiotherapy
reduce tumor size to make primary treatment easier is more effective

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37
Q

What are the differnet types of chemotherapy?

A
  • DNA-damaging agents
  • Alkylating agents
  • Antimetabolites
  • Purine antagonists
  • Pyrimidine antagonists
  • Antimitotics
  • Taxanes and vinca alkaloids
  • Antitumor antibiotics
  • Intercalating agents (anthracyclines) – doxorubicin and
    daunorubicin
  • DNA-repair enzyme inhibitors
  • PARP inhibitors 29
38
Q

What functional groups do alkylating agents work on?

A

N7 and O6 of the guanine

39
Q

What are the alkylating agents?

A
  • Nitrogen mustards
  • Melphalan, Cyclophosphamide, Ifosfamide, Chlorambucil and
    Estramustine
  • Nitrosoureas
  • Carmustine, Lomustine, Nimustine and Streptozocin (Streptozotocin)
  • Platinum drugs
  • Carboplatin, Cisplatin, and Oxaliplatin
  • Miscellaneous alkylating drugs
  • Busulfan, Procarbazine, etc.
40
Q

What replaces the two clorine functional groups on the nitrogen mustard alkylating agents?

A

Two guanines

41
Q

What functional group gets cleaved on the Streptozocin?

A

Methyl group attached to the nitrogen

42
Q

How do the platinum alkylating agents work?

A

Alkylate and crosslink DNA (intra and inter)
cell cycle non specific

43
Q

True or false
DNA-protein cross links are very common with platinum alkylating agents

A

False
They are not common

44
Q

Explain busulfan MOA?

A

remove mesylate(CH3 SO3-) to form R-CH2+ ( non specific alkylating agent

45
Q

What conditions do we use busulfan to treat?

A

Chronic myelgenous leukemia

46
Q

Explain procarbozine MOA?

A

The methyldiazonium ion (CH 3-N+≡N) and methyl cation (CH 3+) gets dealkylated
Non specific alkylating agent which methylates guanine at O6

47
Q

What type of synthesis does procarbozine inhibit?

A

Protein - RNA - DNA

48
Q

In what conditions do we use procarbozine?

A

Hodgkin’s lymphoma (stages III and IV), non-hodgkins lymphoma and gliomas

49
Q

What are antimetabolites?

A

prevent the biosynthesis of normal cellular metabolites

50
Q

What are some types of antimetabolites?

A

Pyrimidine a. - purine a. - fulic acid analouges …

51
Q

What is the main antimetabolite?

A

Uracil

52
Q

What is the MOA of antimetabolite Cytrabine?

A

Inhibit the conversion of cytidylic acid to 2’-deoxycytidylic acid
DNA dependent DNA polymerase
Miscoding due to incorporation into DNA/RNA
Effective during S-Phase -> cell apoptosis

53
Q

Name two types of antimitotics and their site of action?

A

Paclitaxel = breast, lung, and ovarian cancers
Docetaxel = breast, lung, stomach, prostate, and head and neck
cancers

54
Q

What is the mechanism of action of antimitotics?

A

bind to free tubulin
produce stable microtubules
inhibit microtuble disassembly (major function)
microtubules arrange in a parallel fashiom rather than a spindle

55
Q

What are some vinca alkaloids?

A

Vinblastine, vincristine, vindesine and vinorelbine

56
Q

What do vinca alkaloids prevent?

A

Microtube polymerization

57
Q

True or false.
Vinca alkolides have the opposite MOA of taxanes

A

True

58
Q

what conditions do vinca alkaloids treat?

A

Hodgkin’s lymphoma, non-small cell lung
cancer, bladder cancer and melanoma

59
Q

What is the dosage form of vinca alkolides?

A

IV

60
Q

What are some antitumor antibiotics?

A

Daunorubicin, doxorubicin, epirubicin, idarubicin and
mitoxantrone

61
Q

What do anthracyclines do ?

A

DNA intercalating agents

62
Q

What’s the MOA of anthracyclines?

A
  • Intercalate with DNA perpendicular to its longitudinal axis
  • Cause single and double stranded DNA cleavage
63
Q

What are PARP and PARP inhibitors? Provide the drug MOA

A

PARP = Poly(ADP-ribose) polymerase
-> its main fxn is involved in DNA repair

PARP inhibitors are DNA repairing enzyme inhibitors
-> they block DNA repair in cancer cells and cause cancer cell death (PARP is overexpressed in many cancers)

64
Q

What happens to our normal cells in the body during PARP treatment?

A

Nothing, the drug only targets PARP which is only in cancer cells
Our cells have different repair systems

65
Q

What is targeted therapy and what are the goals of targeted therapy?

A

To slow down cancer growth, kill cancer cells, and relieve sx caused by cancer
We can use small molecule agents and monoclonal antibodies to do this

66
Q

What are the four main examples of targeted therapy agents?

A

Tyrosine kinase inhibitors (TKIs) -tinib
Monoclonal antibodies -mab
Apoptosis-inducing agents (bortezomib and oblimersen)
Angiogenesis inhibitors (bevacizumab and sunitinib)

67
Q

What is the TK domain?

A

The tyrosine kinase domain is present in growth factor receptors, such as epidermal growth factor receptor (EGFR) and vascular endothelial growth factor receptor (VEGFR), and signaling protein kinases such as Ras and Raf

68
Q

What does imatinib treat? How does it work?

A

Treats chronic myelogenous leukemia (CML) and acute lymphocytic leukemia (ALL)

It inhibits BCR-ABL tyrosine kinase and inhibits proliferation and induces apoptosis in BCR-ABL positive cells

69
Q

What is gefitinib prescribed for? How does it work?

A

It is for non-small cell lung cancer (NSCLC) with EGFR exon 19 deletion or exon 21 L858R mutation

It inhibits epidermal growth factor receptor (EGFR). Blocks it

70
Q

What does EGF-EGFR signaling promote?

A

DNA synthesis, proliferation, migration, and survival of cells

From the image: proliferation, invasion, angiogenesis, metastasis, resistance to apoptosis

71
Q

What does the monoclonal antibody trastuzumab target? Explain the significance of the target

A

Her2
Her2 is highly expressed in breast cancer patients

72
Q

Where does trastuzumab bind to?

A

Binds to the subdomain IV of Her2 protein (the protein helps with the dimerization of Her2)

73
Q

What type of drug is pertuzumab and where does it bind to? What is the function of the drug?

A

It is another monoclonal antibody
Binds to the subdomain II of Her2 protein

Blocks homodimerization of Her2 and heterodimerization of Her2-Her3
Inhibits Her2-singalling pathway and decreases cells growth

74
Q

What can be used for metastatic and recurrent Her2+ breast cancer?

A

Trastuzumab + pertuzumab + docetaxel

75
Q

What is T-DM1?

A

Ado-trastuzumab emtansine, it is a conjugate of trastuzumab and emtansine

it treats Her2+ metastatic breast cancer and early-stage Her2+ breast cancer after surgery

76
Q

What is Emtansine of T-DM1?

A

It is a potent cytotoxic agent, it cleaved from T-DM1 and release inside breast cancer cells

77
Q

What are apoptosis-inducing agents? Provide an example

A

Proteasome inhibitor and apoptosis-inducing agent
Binds to 26S proteasome, prevent proteosome-mediated degradation of pro-apoptotic factors and induce apoptosis (we are keeping/saving the proteins that induce apoptosis)

Ex) Bortezomib

78
Q

What can apoptosis-inducing agents treat?

A

Treat multiple myeloma and mantle cell lymphoma (B-cell non-Hodgkin lymphoma)

the difference bet Hodgkin and non-Hodgkin is the presence of Reed-Sternberg cells (lymphocytes with 2-3 nuclei inside)

79
Q

What do angiogenesis inhibitors do? Provide an example

A

Block vascular endothelial growth factor (VEGF)
VEGF and its receptors can induce and promote angiogenesis

The ultimate goal here is to starve cancer cells

Ex) bevacizumab

80
Q

What can angiogenesis inhibitors treat?

A

Various types of cancer such as colon cancer and lung cancer

81
Q

What is sunitinib?

A

Multiple-targeted tyrosine kinase inhibitor

Inhibits VEGFR (receptor), platelet-derived growth factor receptor (PDGFR), colony stimulating factor receptor (CSFR) and tyrosine-protein kinase KIT (CD11&)

Angiogenesis inhibitor

82
Q

What can sunitinib be used to treat?

A

Prescribed for renal cell carcinoma, imatinib-resistant gastrointestinal stromal tumor and metastatic pancreatic cancer

83
Q

What is immunotherapy?

A

Stimulate immune system to fight cancer

84
Q

What are the immune system components?

A

Surfaces - protect body against foreign substances
- Skin, mucous memb, tonsils

Internal organs
- Spleen, thymus, bone marrow, lymph nodes

85
Q

Compare and contrast the innate immune response and the adaptive immune response

A

Innate:
nonspecific immune response
response is immediate
recruit immune cells to infxn site to release chemical factors such as cytokines
send antigens to adaptive immune sys

Adaptive:
create immunological memory
recognize specific antigen
takes 4-7 days to respond

86
Q

What are the cells that overlap between the innate and adaptive responses?

A

T cell and Natural killer T cell

87
Q

What is PD-1?

A

PD-1 = programmed cell death protein 1
Surface protein on T-cells
Prevents T-cells from other cells upon binding PD-L1
Check immune responses

88
Q

What are PD-L1 cells?

A

Programmed cell death ligand 1
Prevents T-cells from killing PD-L1 containing cells (ex. pregnant woman - we don’t want immune sys to attack the baby)
upregulated in cancer cells

89
Q

Explain hormonal therapies

A

Hormones can bind estrogen receptor (ER) and progesterone receptor (PR) to promote cancer cell growth
Hormonal therapies are used for breast cancer cells with the expression of ER and PR

90
Q

What is Tamoxifen?

A

It is a hormonal therapy

Blocks ER and inhibits breast cancer cell growth
May slightly increase the chance of getting uterine cancer

91
Q

Name the three PD-1 inhibitors

A

Pembrolizumab
Nivolumab
Cemiplimab

92
Q

Name the three PD-L1 inhibitors

A

Atezolizumab
Avelumab
Durvalumab

PHAR 123* (11 decks)

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