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Pharmacology > Exam3Lec5CancerChemotherapyI > Flashcards

Exam3Lec5CancerChemotherapyI Flashcards

1
Q

What is squamous cell carcinoma of the lung caused by?

A

Cigarette smoking and keratin pearls

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2
Q

Is adenocarcinoma caused by smoking?

A

NO

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3
Q

What is malignant melanoma?

A

Local invasion and lymph node metastasis. The deeper it is, the worse the prognosis.

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4
Q

What are the most new cases of malignant cancer for males and females?

A

Males: prostate
Females: breast

pancreatic cancer is very rare but one of the most lethal caners

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5
Q

Which cancer(s) have the highest death rate?

A

Lung and Bronchus

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6
Q

What induces mesothelioma directly?

A

Abestos

mesothelima=cancer covering outside lung

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7
Q

Abestos incr the risk of what cancer?

A

increases the risk of Squamous cell carcinoma in conjunction with cigarette smoking

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8
Q

Does smoking increase the risk of mesothelioma?

A

NO

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9
Q

What are key disposing factors of Heptacellular carcinoma?

A
  1. Chronic Hepatitis B
  2. Chronic Hepatitis C
  3. Alcoholism
  4. Aflatoxin exposure

epithelium have a glandualr appearance,

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10
Q

Most cancer therapies are designed to be ____ toxic to malignant tumor cells

A

directly

try to kill tumor cells w/o injuring good normal cells

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11
Q

What do most cancer therapies affect?

A
  • affect** DNA or RNA synthesis** and protein synthesis dowstream to affect tumor cell proliferation or survival.
  • also affect normal cells and thus, both abnormal and normal cell proliferation is blocked, leading to toxicities
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12
Q

Basic Principles of Cancer Chemotherapy

Definition of each:
Adjuvant chemotherapy
Neoadjuvant chemotherapy
Maintenance chemotherapy

A
  • Adjuvant chemotherapy: chemo as a supplemental therapy following/after surgery and/or radiation
  • Neoadjuvant chemotherapy: chemo given prior to surgery
  • Maintenance chemotherapy: chemo given in lower doses to facilotate long term remission
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13
Q

True or false: rapidly dividing cells are generally more sensitive to chemo and radiation therapy

A

true

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14
Q

Tumor cells can find sanctuary in tiscues such as the?

A

CNS-necessitating treatment there

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15
Q

What is a major goal of cancer therapy?

A

to remove or destroy all malignant cells and convert the malignancy into a chronic disease (i.e. palliation)

chronic disease could be HTN, diabetes, etc

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16
Q

What is a big problem with chemotherapy?

A

Tumor cell resistance

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17
Q

Because of tumor cell resistance how is chemotherapy given?

A

pt given a combination of chemotherapeutic regimens

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18
Q

Tumor cells acquire additonal ____ to resist drugs

A

mutations

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19
Q

Multidrug resistance from tumor cells can occur by what?

A

amplification of P- glycoprotein (MDR1) that pumps drug out of the cell.

This is an ABC family co-transporter, that induces efflux of drugs from cells in an ATP-dependent manner

hy

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20
Q

Because tumor cells acquire additional mutation to resist drugs, what is done to minimize that?

A

resistance is minimized by short-term, intermittent therapy with drug combinations

try to treat with alternative combinations of drugs so you can try and kill the mutated tumor early on

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21
Q

What are 4 key complication of cancer therapeutics?

A
  1. Bone marrow suppression
  2. Stomatitis (ulcers in mouth)
  3. Nausea and severe vomiting
  4. Hair loss
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22
Q

What are 3 specific complications (side effects) of cancer therapeutics?

hy

A
  1. Cyclophosphamide- severe cystitis
  2. Doxorubicin- cardiotoxicity
  3. Bleomycin- pulmonary fibrosis

hy

cystis: inflammation of bladder and hemorrhage

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23
Q

Which drugs causes major and mild myleosuppression?

A

Major: Cyclophsphamide and Doxorubucin
Mild: Bleomycin

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24
Q

Side effects of Cisplatin

A
  1. Ototoxicity
  2. Nephrotoxicity
  3. Nausea/vomiting
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25
Q

Side effects of Doxorubucin

A

cardiotoxicity

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26
Q

Side effects of Bleomycin

A

Pulmonary toxicity

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27
Q

Side effects of Cyclophosohamide

A

Hemorrhagic cystitis

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28
Q

Side effects of Oxaliplatin/Vincrisitne/ Taxanes

A

peripheral neuropathy

taxol for breast cancer
microtubule inhibitor, can change stability of the tubule

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29
Q

What are the hallmarks of cancer? (what a malignant cells need to have

A
  1. Sustaining proliferative signaling ( K-RAS)
  2. Evading growth supressors (cell cycle-P53)
  3. Activating invasion and metastasis
  4. Enabling replicative immortality ( Telomerase/TERT)
  5. Inducing angiosgenesis (VEGF)
  6. Resisting cell death
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30
Q

True or false: Tumor cells interact w/ host

A

True, normal cells play a role and how they are responding to tumor cells

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31
Q

What is the greatest focus of therapeutic intervention?

A

Avoiding immune destruction

32
Q

Adenoma to Carcinoma Sequence in Colon Cancer development

A
  1. Mutates in the APC gene 1st
  2. APC gene 2nd
  3. K-RAS third and serves as the driver, where it becomes an adenoma (overgrowth w/polyps, still benign)
  4. Loose P53 (loss of inhibition) turns into carcinoma
  5. You can get additional mutations of telomerase
33
Q

What is Adenomatous polyposis?

A

A precursor for colonic adenocarcinoma

colonoscopy: look for polpys

34
Q

What is familial polyposis?

A

A genetic cause of colonic adenocarcinoma. Mutation of APC gene: 5q-autosomal dominant disease

mutation of APC, 100% will get colon cancer bc its 1 allele

35
Q

Conversion of normal human fibroblasts and epithelial cells into malignant tumor cells requires 4 genes. What are they?

turning fibroblasts into tumor cells

A

The 4 genes activated:
1. Ras
2. SV40 large T antigen
3. SV40 small t antigen
4. TERT (telomerase)

when these 4 are mixed, in turns into tumor cells

36
Q

Chronic myelegenous leukema (CML)
Transolocation
Affected genes

A

Transolocation: (9;22) (q34;q11)
Affected genes: ABL9q34, BCR22q11

37
Q

Acute Myeloid Leukemia (AML)
Transolocation
Affected genes

A

Transolocation: (8;21) (q22;q22) (15;17) (q22;q21)
Affected genes: AML8q22, ETO21q22, PML1q22, RARA17q21

38
Q

Burkitt Lymphima (Epstein Barr)
Transolocation
Affected genes

A

Transolocation: (8;14) (q24;q32)
Affected genes: MYC 8q24, IGH14q32

39
Q

Follicular Lymphoma
Transolocation
Affected genes

A

Transolocation: (14;18) (q32;q21)
Affected genes: IGH 14q32, BCL2 18q21

40
Q

List how each of these genes play a role in being converted into a malignant state
1. Ras
2. SV40 large T antigen
3. SV40 small t antigen
4. TERT (telomerase)

A
  1. Ras:stimulates signal transduction
  2. SV40 large T antigen: blocks the cell cycle inhibitors p53 and Rb
  3. SV40 small t antigen: blocks the activity of protein phosphatase 2A (PP2A)
  4. TERT (telomerase): allows for cell replicative immortality

Transduction of 4 individual genes into normal human cells can convert them into a malignant state.
most cancers have activated RAS and elevated TERT

41
Q

What are specific chromosomal translocation leading to malignancy for Chronic Myleogenous leukemia (CML)?

A

Chr:9:22 Bcr-Abl Philadelphia chromosome
Classic finding: Spenomegaly

42
Q

What are specific chromosomal translocation leading to malignancy for Burkitt’s Lymphoma?

A

Chr:8:14
Myc amplification, pro growth

43
Q

Chemoterapeutic agents

What is a treament for Chronic Myleogenous leukemia (CML)

A

Imatinib: an inhibitor of Abl kinsae

has profound ability to induce remission

44
Q

Imatinib MOA

A

Binds to Abl kinase in its inactive conformation and prevents its activation thus it has less toxciity

leukemic cells can becomen resiisntant to Imatinb through new mutations in Abl in the Bcr-Abl fusion protein

45
Q

What are the new generations of Abl inhibiotrs to treat CML?

A

Dasatinib and Nilotinib (more potent and efficacious than Imatininb in treating CML)

46
Q

What is breast cancer?

A

Invasic ductal carcinoma (invades lymph nodes very easily)

47
Q

What are key genetic changes that underlie the development of breast carcinoma?

A
  • Luminal-> ER+ and HER2-=BRCA2 and PIK3CA mutation
  • HER2 enriched->HER2+= TP53 mutation and HER2 amplification
  • Basal like-> ER- and HER2-= TP53 mutation and BRCA1 inactivation
48
Q

What can identify metastatic carcinoma to a lymph node?

A

immunostaining can identify the malignant cells

how pathologists find tumor and characterize what it is

49
Q

Explain therapeutic targeting of EGF receptor in epithelial cancers.
1. EGFR inhibitors are used for what cancers?
2. EC domain of EGFR?
3. IC domain of EGFR?

A

1.EGFR inhibitors are particularly utilized in breast, lung, and colon cancers.
2.Blocking monoclonal antibodies directed to the extracellular domain of EGFR
3.Chemical inhibitors of the tyrosine kinase activity of the EGFR intracellular domain

-resistance has been observed to both the antibody and chemical EGFR inhibitors

50
Q

Examples of Combination Chemotherapeutic regimens

slide 24

A

Combination Chemotherapeutic regimens are usually different drugs that inhibit diff things + antibodies mixed together

51
Q

Key chemotherapeutic agents: targets and mechanism of action

Protein kinase inhibitors antibodies MOA

ly

A

block activites of signaling pathways

52
Q

Key chemotherapeutic agents: targets and mechanism of action

Immune checkpoint inhibitors MOA

ly

A

block immune evasion

53
Q

Key chemotherapeutic agents: targets and mechanism of action

Hormone antagonits MOA

ly

A

inhibits receptor fxn and expression

54
Q

Key chemotherapeutic agents: targets and mechanism of action

Expothilones,Taxanes, Vinca Alkaloids, Estramustine MOA

ly

A

Inhibit fxn of microtubules

55
Q

Key chemotherapeutic agents: targets and mechanism of action

ATRA, Arsenic trioxine, Histone Deacetylase inhibitors MOA

ly

A

induce differentiation

56
Q

How do chemotherapeutic agents target the cell cycle?

A
  1. Messes up DNA, RNA, and protein synthesis
  2. Trap cells in S-phase where DNA is replicated
  3. Blocks M phase with tubulin (tubulin is needed for chromosome segmentation and for cells to divide)
57
Q

What are the cell cycle specific drugs?

A
  • Antimetabolites
  • Bleomycin
  • Etoposide
  • Vinca alkaloids
58
Q

What are the cell cycle non-specific drugs?

A

Alkylating agents
Antibodies
Cisplatin
Nitosoureas

59
Q

Anti-metabolites chemotherapeutic agents are structurally related to what? What do they interfere with and how?

A
  • Compounds are structurally related to normal compounds
  • Interfere with the availability of purine or pyrimidine nucleotide precursors
  • This interference occurs by inhibiting synthesis or by competing with normal precursors during DNA or RNA synthesis.

enzymes picks them up thinking they are normal cmpds

60
Q

Anti-metabolites chemotherapeutic agents have maximal cytotoxic effecs during what phase of the cell cycle?

A

S-phase (dna replication)

61
Q

True or false: Methotrexate (MTX) is usually used in combination regimens

A

True

mtx is a folate related molecule impt in preganny and closing the neural tube. low folate-anema (nned for RBC production)

62
Q

MTX is used in which cancers?

A

ALL, Burkitt’s lymphoma, breast cancer and other solid tumors

63
Q

-5-FU anti-metabolite is used for which cancer(s)?

A

used in slowly growing tumors including colon, breast, ovarian, pancreatic and gastric cancers

64
Q

-5-FU is coadministered with what?

A

leucovorin to enhance inhibition of thymidylate synthase

65
Q

MOA of MTX anti-metabolites

A

MTX targets dihydrofolate reductase, which is necessary to create reduced folate isoforms, FH2, FH4, and N5, N10- methylene-FH4 that are required to generate dTMP

blocks synth if folate isoforms that are requires to generate dTMP

66
Q

-5-FU anti-metabolite MOA

A

5-FU targets thymidylate synthase which generates dTMP from dUMP, a reaction that also requires N5, N10-methylene-FH4

TS generates dTMP from dUMP) requires requires N5, N10-methylene-FH4

67
Q

Leucovorin (N5-formyl-FH4) anti-metabolite MOA

A

converted to N5, N10- methylene-FH4 and bypass the effects of MTX, which can cause key side effects including megaloblastic anemia

68
Q

Capecitabine (anti-metabolite)

A

Metabolized to 5-FU can show less toxicity due to more selective conversion to 5-FU within the tumor.

69
Q

Cytarabine (anti-metabolite) MOA

A

acts as pyrimidine antag. inhibits DNA polymerase, used to treat AML

70
Q

Azacitidine (anti-metabolite) MOA

A

acts as a pyrimidine analog, inhibits RNA processing, used to treat AML

71
Q

Gemcitabine (anti-metabolite) MOA

A

Used in pancreatic cancer and non-small cell lung cancer therapy, metabolites block DNA synthesis

72
Q

Which of the following is repsonsible for the multidrug resistance exhibited by some cancers?
A. p-glycoprotein
B. CDK4
C. RAS
D. MYC

A

A. p-glycoprotein

73
Q

Ototoxicity, nephrotoxicity, nausea, and vommiting are side effects of which chemotherapeutic?
A. Bleomycin
B. Doxorubicin
C. Taxanes
D. Cisplatin

A

D. Cisplatin

74
Q

Translocation of the BCR-ABL genes is characteristic of which cancer?
A. AML
B. Burkitt Lymphoma
C. CML
D. Follicular Lymphoma

A

C. CML

75
Q

Anti-metabolites maximally effect which phase of the cell cycle?
A. G1
B. S
C. G2
D. M

A

B. S

76
Q

Tumor cells can find sanctuary in tisues such as the?

A

CNS-nesessitating treatment there

Pharmacology (26 decks)

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