Chapter 11: Oncology Flashcards
MC cancer related death in women
Lung cancer
MC Cancer in men
Prostate cancer
Need MHC complex to attack tumor
Cytotoxic T cells
Can independently attack tumor cells
Natural killer cells
Tumor marker: colon ca
CEA
Tumor marker: liver CA
AFP
Tumor marker: pancreatic CA
CA 19-9
Tumor marker: Ovarian ca
CA 125
Tumor marker: testicular Ca, choriocarcinoma
Beta-HCG
Tumor marker: prostate CA
PSA
Prostate CA: thought to be tumor marker with the highest sensitivity, although specificity is low
PSA
Tumor marker: small cell lung CA, neuroblastoma
NSE
Tumor marker: breast CA
BRCA I and II
Tumor marker: carcinoid tumor
Chromogranin A
Tumor marker: thyroid medullary CA
Ret oncogene
Half life: CEA
18 days
Half life: PSA
18 days
Half life: AFP
5 days
Oncogenesis: time between exposure and formation of clinically detectable tumor
Latency period
Three phases of latency period
- Initiation (carcinogen acts with DNA)
- Promotion (then occurs)
- Progression (cancers cells to clinically detectable tumor)
What do retroviruses contain?
Oncogenes
Associated with Burkitt’s lymphoma (8:14 translocation) and nasopharyngeal CA (c-myc)
Ebstein-Barr Virus
Infectious agent: nasopharyngeal carcinoma
EBV
Infectious agent: Burkitt’s lymphoma
EBV
Infectious agent: various lymphomas
HIV
Most vulnerable stage of cell cycle for XRT
M phase
Radiation therapy: what causes most of the damage?
Most damage to DNA done by formation of oxygen radicals -> maximal effect with high oxygen levels
How does high-energy radiation have a skin–preserving effect?
Maximal ionizing potential not reached until deeper structures
What do fractionate XRT doses allow?
- Repair of normal cells
- Re-oxygenation of tumor
- Redistribution of tumor cells in the cell cycle
Very radiosensitive tumors
Seminomas, lymphomas
Very radioresistant tumors
Epithelial, sarcomas
Brachytherapy
Source of radiation in or next to tumor (Au-198, I-128); delivers high, concentrated doses of radiation
Chemo Agent: exhibit plateau in cell-killing ability
Cell cycle-specific agents (5FU, methotrexate)
Chemo Agent: Linear response to cell killing
Cell cycle-nonspecific agents
Chemo Agent: Decreases short-term (5 year) risk of breast CA 45%
Tamoxifen (blocks estrogen receptor)
Complications: tamoxifen therapy
1% risk of blood clots
0.1 % risk of endometrial cancer
Chemo Agent: promotes microtubule formation and stabilization that cannot be broken down; cells are ruptures
Taxol
Chemo Agent: can cause pulmonary fibrosis
Bleomycin
Busulfan
Chemo Agent: nephrotoxic, neurotoxic, ototoxic
Cisplatin (platinum alkylating agent)
Chemo Agent: bone (myelo) suppression
Carboplatin (platinum alkylating agent) and
Vinblastine (microtubule inhibitor)
Chemo Agent: peripheral neuropathy, neurotoxic
Vincristine (microtubule inhibitor)
Cyclophosphamide
Alkylating agent: transfer alkyl groups; forms covalent bonds to DNA
- Acrolein is the active metabolite.
- Side effects: gonadal dysfunction, SIADH, hemorrhagic cystitis
Tx: hemorrhagic cystitis s/t cyclophosphamide
Mesna
Chemo Agent: antihelminthic drug thought to stimulate immune system against cancer
Levamisole
Methotrexate
Chemo Agent: inhibits dihydrofolate reductase (DHFR), which inhibits purine and DNA synthesis
- Side effects: renal toxicity, radiation recall
Reverses effects of methotrexate by re-supplying folate
Leucovorin rescue (folinic acid)
5-fluorouracil (5FU)
Chemo Agent: inhibits thymidylate synthetase, which inhibits purine and DNA syntehsis
Increases toxicity of 5-fluorouracil
Leucovorin (folinic acid)
Doxorubicin
Chemo Agent: DNA intercalator, oxygen radical formation
Side effects: doxorubicin
Heart toxicity secondary to oxygen radicals at total doses > 500 mg/m^2.
Etoposide (VP-16)
Chemo Agent: inhibits topoisomerase (which normally unwinds DNA)
Chemo Agents: least myelosuppression
Bleomycin, vincristine, busulfan, cisplatin
GCSF (granulocyte colony-stimulating factor
Used for neutrophil recovery after chemo
Side effect - Sweet’s syndrome (acute febrile neutropenic dermatitis)
When to consider resection of a normal organ to prevent cancer -> breast
BRCA I or II with strong family history
When to consider resection of a normal organ to prevent cancer -> thyroid
RET proto-oncogene with family history thyroid cancer
Tumor suppressor gene: chromosome 13; involved in cell cycle regulation
Retinoblastoma
p53
Tumor suppressor gene: chromosome 17; involved in cell cycle
Normal gene induces cell cycle arrest and apoptosis; abnormal gene allows unrestrained cell growth
APC
Tumor suppressor gene: chromosome 5, involved with cell cycle regulation and movement
DCC
Tumor suppressor gene: chromosome 18; involved in cell adhesion
bcl
Tumor suppressor gene: involved in apoptosis (programmed cell death)
Chromosome: p53
17
Chromosome: APC
5
Chromosome: DCC
18
ras
Proto-oncogene: G protein defect
src
Proto-oncogene: tyrosine kinase defect
sis
Proto-oncogene: platelet-derived growth factor receptor defect
erb B
Proto-oncogene: epidermal growth factor receptor defect
myc (c-myc, n-myc, l-myc)
Proto-oncogenes: transcription factors
Li-Fraumeni syndrome
Defect in p53 gene -> patients get childhood sarcomas, breast CA, brain tumors, leukemia, adrenal CA
Colon cancer
- Gene involved in development include APC, p53, DCC, and K-ras
- APC though to be initial step in evolution
- Does not usually go to bone
Carcinogens: coal tar
Larynx, skin, bronchial CA
Carcinogens: beta-naphthylamine
Urinary tract CA (bladder CA)
Carcinogens: benzene
Leukemia
DDX: suspicious supraclavicular node
Neck, breast, lung, stomach (Virchow’s node), pancreas
DDX: suspicious axillary node
Lymphoma (#1), breast, melanoma
DDX: suspicious periumbilical node
Pancreas (Sister Mary Joseph’s node)
DDx: ovarian metastases
Breast (#1), prostate
DDx: skin metastases
Breast, melanoma
DDx: small bowel metastases
Melanoma (#1)
Clinical trials:
- Phase 1
- Phase 2
- Phase 3
- Phase 4
- Phase 1: Is it safe and at what dose?
- Phase 2: Is it effective?
- Phase 3: Is it better than existing therapy?
- Phase 4: implementation and marketing
What is induction therapy?
Sole treatment; use for advanced disease or when no other treatment exists
En bloc multiorgan resection
Can be attempted for some tumors (colon into uterus, adrenal into liver, gastric into spleen); aggressive local invasiveness is different from metastatic disease
Colon metastases to the liver: prognosis
35% 5-year survival rate if successfully resected
Prognostic indictors for survival after resection of hepatic colorectal metastases
Disease-free interval > 12 months, tumor number
One of the few tumors for which surgical debunking improves chemotherapy (not seen in other tumors)
Ovarian CA
Curable solid tumors with chemotherapy only
Hodgkin’s and non-Hodgkin’s lymphoma
T cell lymphomas
HTLV-1 (skin lesions) Mycosis fungoides (Sezary cells)
HIV related malignancies
Kaposi’s sarcoma, non-Hodgkin’s lymphoma
Causes angiogenesis; involved in tumor metastasis
V-EGF (Vascular epidermal growth factor)
