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Review / Wrong Answers > DIT review - Oncology 1 > Flashcards

DIT review - Oncology 1 Flashcards

1
Q

Describe the role of Cyclin D in cell replication

A

o Cyclin D activates CDK4 (kinase complex)

o This kinase complex will phosphorylate Rb protein

o Phosphorylated Rb becomes unbound from transcription factor E2F, allowing cell to progress from G1 to S phase

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2
Q

What is the most common oncogene?

A

RAS

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3
Q

What cancers are associated with RAS mutation?

A

Pancreatic adenocarcinoma

Cholangiocarcinoma

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4
Q

What is the most common tumor suppressor mutation?

A

p53 mutation

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5
Q

Is RB a tumor suppressor or an oncogene, and what tumors is it associated with>

A
  • Tumor suppressor
    • Blocks transition from G1 to S phase and G2 to M phase
    • Causes apoptosis by inducing the transcription of pro-apoptotic genes (such as BAX)
  • Associated with:
    • Retinoblastoma
    • Osteosarcoma
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6
Q

What is the oncogene and tumor suppressor associated with breast cancer

A

Oncogene = Her2

Tumor suppressor = BRCA1/2

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7
Q

What cancer is associated with c-MYC mutation

A

Burkitt lymphoma

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8
Q

What cancer is associated wth BCR-ABL mutation?

A
  • BCR-ABL
    • Oncogene
    • t(9;22) – Philadelphia chromosome
    • Associated with
      • Chronic myelogenous leukemia (CML)
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9
Q

What tumor will be CEA+

A

Colon cancer

Pancreatic cancer

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10
Q

What cancer will be CA 19-9+

A

Pancreatic cancer

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11
Q

What cancer will be alpha-fetoproteion (AFP)+

A

Hepatocellular carcinoma

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12
Q

What cancer will be CA-125+

A

Ovarian cancer

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13
Q

What cancer will be S-100+

A

S-100 = marker of neural crest

Melanoma

Schwannoma

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14
Q

What cancer will be alkaline phosphatase +

A

Metastasis to bone

Biliary disease

Paget disease of the bone

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15
Q

In what diseases will you see Psammoma bodies?

A

Papillary thyroid carcinoma

Serous cystadenocarcinoma of the ovary

Mesothelioma

Meningioma

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16
Q

What tumors secrete erythropoietin

A
  • Potentially Really High Hematocrit
    • Pheochromocytoma
    • Renal cell carcinoma
    • Hepatocellular carcinoma
    • Hemangioblastoma
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17
Q

Describe the synthesis of the pyrimidine, thymidine

A
  • Glutamine + CO2 + ATP converted to carbamoyl phosphate via carbamoly phosphate synthetase II
  • Carbomoyl phosphate converted to orotic acid
  • Orotic acid converted to UMP via UMP synthase
  • UMP to UDP
  • UDP to dUDP via ribonucleotide reductase
  • dUDP to dUMP
  • dUMP methylated to dTMP via thymidilate synthase
    • THF is what provides the carbon needed for methylation (THF to DHF)
    • Thymidylate synthase catalyzes the transfer of methyl group
    • DHF gets converted back to THF via dihydrofolate reductase
    • THF is then re-methylated to continue the cycle
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18
Q

MOA of Methotrexate

A
  • Folate analog that competitively and irreversibly binds to dihydrofolate reductase, preventing convserion of DHF into THF
  • Inhibition of DHF reductase leads to a build-up of DHF
  • This means you have no THF to create dTMP
    • Interferes with the synthesis of DNA, RNA, and other rapidly dividing cells
    • Rapidly dividing cells are the ones that are preferentially targeted
    • Most effective during S phase (when cells are undergoing synthesis of new DNA)
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19
Q

Uses of Methotrexate

A
  • Multiple malignancies
    • E.g. leukemias, lymphomas, breast cancer, head and neck cancer, lung cancer
  • Other diseases characterized by abnormal cellular proliferation:
    • Abortifacient (MTX + Misoprostol)
      • Inhibits trophoblast cellular division, hindering implantation and encouraging expulsion
    • Early, unruptured ectopic pregnancy
    • Molar pregnancy trophoblastic tumors, choriocarcinoma
    • Psoriasis (hyperproliferation of epidermis)
  • Chronic inflammatory conditions (can inhibit proliferation of immune cells)
    • Rheumatoid arthritis (disease modifying antirheumatic drug – DMARD)
    • Immunosuppressive thereapy (e.g. IBD, lupus, vasulitits, dermatomyocytis)
20
Q

Adverse effects of Methotrexate

A
  • Folate deficiency
  • Megaloblastic anemia
  • Myelosuppression and Pancytopenia
  • Increased risk of infection due to immunosuppression
  • Pulmonary fibrosis (restrictive lung disease)
  • Hepatotoxicity (should monitor LFTs)
  • Alopecia
  • Mucositis
21
Q

How do you reverse the toxicity of Methotrexate

A
  • Leucovorin (folinic acid – reduced form of folate)
    • Sketchy = lucky feline (cat statue)
    • Can be used to reverse the toxicity effects of MTX (“leucovorin rescue”)
    • Folinic acid does not require DHF reductase
22
Q

MOA of 5-Fluorouracil (5-FU)

A
  • 5-FU is a cytotoxic pyrimidine analog
    • 5-FU is metabolized by intracellular reaction to it’s active form FDuMP
    • FDUMP forms a complex with THF and inhibits thymidylate synthase (conversion of dUMP to dTMP using carbon from THF)
    • Inhibition of thymidylate synthase by 5-FU will lead to a build-up of dUMP
23
Q

Adverse effects of 5-FU

A
  • Diarrhea (cytotoxic damage to rapidly dividing cells of intestinal mucosa)
  • Photosensitivity
  • Myelosuppression and Pancytopenia
  • Increased risk of infection due to immunosuppression
24
Q

MOA of hydroxyurea

A
  • Recall:
    • The precursor of all pyramidine nucelotides is UMP, which is then phosphorylated to UDP
    • Ribonucleotide reductase will convert UDP to dUDP
    • dUDP can then be de-phosphorylated into dUMP
  • Hydroxyurea works by inhibiting ribonucleotide reductase so that UDP cannot be converted to dUDP, thus blocking the de novo synthesis of thymidine
25
Q

MOA of Azathioprine

A
  • Is a prodrug of the cytotoxic purine analog 6-mercaptopurine (6-MP)
  • AZA must be activated to 6-MP via hypoxanthine-guanine phosphoribosyl transferase (HGPRT)
  • AZA/6-MP act by blocking the synthesis of IMP = decreased de novo purine nucleotide synthesis = blocked DNA and RNA synthesis
  • Decreased GMP = decreased B- and T-cell proliferation + decreased antibodies
26
Q

MOA of Mycophenolate Mofetil

A
  • Is an IMP dehydrogenase inhibitor, preventing conversion of IMP to GMP
  • Activated lymphocytes are dependent on de novo synthesis of purine nucleotides
27
Q

MOA of Cladribine

A
  • Sketchy:
    • caveman clad in bear skin
  • Cytotoxic purine analog (–> purine stone hammer)
    • Is resistant to adenosine deaminase, enzyme that normally degrades purine analogs
  • Can incorporate into DNA causing
    • DNA breaks
    • Inhibition of DNA synthesis and repair by inhibiting DNA polymerase alpha and beta
28
Q

Uses of Cladribine

A

Hairy cell leukemia

Other leukemias and lymphomas

29
Q

MOA of Cytarabine

A
  • Sketchy = saber toothed tiger
  • Cytotoxic pyrimidine analog (hexagon spots on tiger)
  • Inhibits DNA pol alpha and beta
30
Q

Uses of Cytarabine

A

Only useful against hematologic malignancies (not solid tumors)

31
Q

MOA of Gemcitibine

A
  • Sketchy = geods with gems inside
  • Mechanism of action
    • Cytotoxic pyrimidine analog
    • After being converted to triphosphate form, it inhibits DNA pol alpha and beta, blocking DNA synthesis and repair
32
Q

Uses of Gemcitibine

A
  • Active against both hematologic malignancies AND solid tumors
33
Q

Adverse effects of all drugs that block DNA polymerase (Cladribine, Gemcitibine, Cytarabine)

A

Myelosuppression

Increased risk of infection

34
Q

What are the alkylating agent anti-neoplastics?

A

Cyclophosphamide - cyclops

Busulfan - beautiful sirens

Nitrosoureas - centaurs (“-mustine” - mustang)

35
Q

MOA of Cyclophosphamide

A
  • Mechanism of action:
    • Works by attaching an alkyl group to the guanine base of DNA at the #7 nitrogen atom
    • This leads to intra- and inter-strand cross-links
    • Cell division halts and the cell undergoes apoptosis
    • This is cell cycle NON-specific
36
Q

Uses of Cyclophosphamide

A
  • Hematologic and solid malignancies (e.g. leukemias and lymphomas, breast cancer, ovarian cancer
  • Immunosuppressive (e.g. nephrotic syndrome, nephritic syndrome, vasculitis, autoimmune hemolytic anemia)
37
Q

Adverse effects of cyclophosphamide

A
  • Myelosuppression (leading to cytopenias)
  • Hemorrhagic cystitis
    • Cyclophosphamide is metabolized by the kidney into a molecule that is toxic to uroepithelial cells if in contact with the cells for too long
  • Increased risk for bladder cancer (high grade transitional cell carcinoma)
  • Hyponatremia due to SIADH
  • Toxic to ovaries and testes
    • Can cause infertility and premature menopause
    • Can cause decrease in sperm count and irreversible azoospermia
38
Q

How do you prevent hemorrhagic cystitis from use of Cyclophosphamide

A
  • Prevent with aggressive hydration and co-administration with 2-mercaptoethanesulfonate (MESNA), which will bind and inactivate the toxic metabolite
    • Cyclophosphamide is metabolized by the kidney into a molecule that is toxic to uroepithelial cells if in contact with the cells for too long
39
Q
A
40
Q

MOA of Busulfan

A
  • Sketchy = beautiful sirens
  • Alkylating agent that forms DNA intra-strand cross-links, preventing DNA replication and leading to apoptosis
41
Q

Uses of Busulfan

A
  • Used as a conditioning agent prior to bone marrow transplant – aka significantly depletes the bone marrow
42
Q

Adverse effects of Busulfan

A
  • Lung toxicity (e.g. acute lung injury, interstitial fibrosis, alveolar hemorrhage)
  • Skin darkening (“busulfan tan”)
43
Q

Names of nitrosourea drugs

A

Sketchy = centaurs

  • Drugs:
    • “-mustine**” suffix (e.g. **Carmustine, Lomustine)
        • centaur is a mustang horse
    • Streptozotocin
        • striped zebra centaur
44
Q

MOA of nitrosoureas

A
  • Alkylating agents that form DNA cross links, preventing DNA replication and leading to apoptosis
45
Q

Uses of nitrosoureas

A
  • Brain tumors (e.g. glioblastoma multiforme)
    • Are highly lipophilic so can cross the BBB
46
Q

Adverse effects of nitrosoureas

A
  • Neurotoxicity (e.g. convulsions, dizziness, atazia)

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