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51 Cards in this Set
- Front
- Back
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Hallmarks of Cancer
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Genomic Instability
Inappropriate Cell Proliferation Angiogenesis Invasion Metastasis |
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Recurrence risks of translocations
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Maternal t(14:21) = 10%
Paternal t(14:21) = 5% t(21:21) = 100% |
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Angiogenesis
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Tumours >2mm
Positive regulators - VEGF (regulated by ras oncogene) - bFGF (basic fibroblastic growth factor) Negative regulators - thrombospondin-1 (regulated by p53) |
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Cell adhesion molecules (CAMs)
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Mediate cell interaction with ECM
1 - Integrins: interact with outside env., regulates prolif and apopt 2 - Cadherins: cell-to-cell interaction. Reduced E-cadherin leads to cell detachment |
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Hybrid dysplasia / carcinoma in situ
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Cancer that has not invaded. Does not kill patients.
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Tumor doubling time
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Time for tumor to double in size:
1 - Growth fraction: % of cells in cycle (only 3-15%) 2 - Cell death fraction (75-90% die) |
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Tumor doubling time
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Time for tumor to double in size:
1 - Growth fraction: % of cells in cycle (only 3-15%) 2 - Cell death fraction (75-90% die) |
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Neoplasia
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Abnormal mass of tissue, persisting even after stimulus is removed.
Benign OR malignant. |
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Cancer
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A malignant neoplasm.
Note: cancers that spread to different organs retain characteristics (etiology, pathology, behavior and treatment) and name of organ of origin. |
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Hypertrophy
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Increase in size of cells within an organ. Returns to normal when stimulus is removed.
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Hyperplasia
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Increase in number of cells within an organ.
Returns to normal when stimulus is removed. |
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Atrophy
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Reduction in size or number of cells within an organ.
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Dysplasia
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Pre-malignant - disordered growth and morphology.
Graded as low, medium or high grade (1, 2, 3) depending on severity. |
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High-grade dysplasia
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Synonymous with carcinoma-in-situ.
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CYP Inducers
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St. John's Wort
Phenytoin Rifampin Ethanol Carbamazepine Cigarette Smoke |
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CYP Inhibitors
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Fluoexetine
Erythromycin Ketoconazole Grapefruit Juice |
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Epithelial Neoplasms
Squamous Glandular Transitional Liver Skin |
sq. papilloma / sq. cell carcinoma
adenoma / adenocarcinoma trans. papilloma / trans. carcinoma adenoma / hepatocellular carcinoma papilloma / sq. or basal cell carcinoma |
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Connective Tissue Neoplasms
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Bening: -oma
Malignant: -sarcoma |
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Hemopoeitic and Lymphoid Neoplasms
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Malignant: - lymphoma / leukemia / myeloma
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RB-1
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Tumor suppressor involved with retinoblastoma
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bcr-abl
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'Philadelphia chromosome'
Translocation that inappropriately increases expression of abl oncogene |
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bcl-2
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Reduces apoptosis and supports tumor growth.
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bax
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Promotes apoptosis and may be upregulated, thus slowing cancer.
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Curative cancer treatment
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Surgery: main modality
Radiation: curative for some cancers Systemic: not usually curative on its own, except for some cancers |
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Adjuvant cancer treatment
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Increase probability of cure - kill microscopic disease. Types:
Systemic: (common) - chemotherapy - hormone therapy - biological therapy Radiation: (less common) Surgery: (uncommon) |
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Maintenance cancer treatment
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Delay or prevent relapse
Low dose chemotherapy Molecularly targeted therapy *only used in child cancers |
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Palliative cancer treatment
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Relief of symptoms
Systemic (hormone, chemo) Radiation Surgery (bowel obstruction) Ancillary drugs (eg analgesics) |
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Radiation cancer therapy
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1. Teletherapy or external beam
x-ray generator delivers radiation to a prescribed anatomic site 2. Brachytherapy Radiation source placed in contact with tumor (radioactive seeds inside tumor) 3. Isotope therapy Radioactive isotopes that are used by a particular cell type |
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When to expect hereditary cancers
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>2 close relatives
early age at diagnosis multiple primary tumors bilateral or multiple rare cancers constellation of tumors evidence of dominant transmission |
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BRCA
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Breast cancer gene. Risks:
Breast cancer by 70 yrs: - BRCA1: 50-85% - BRCA2: 50-85% Ovarian cancer by 70 yrs: - BRCA1: 20-50% - BRCA2: <20% |
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HNPCC
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Hereditary Nonpolyposis Colon Cancer
Criteria: a) 3 family members, two of whom are 1st degree b) two successive generations c) one relative diagnosis at <50 yrs |
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FAP
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Familial Adenomatous Polyposis
- dominant - APC gene on chromosome 5 - 100% risk of colon cancer by age 40 - Associated with 100s of polyps - Colonoscopy at 10-16 yrs of age |
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6 Hallmarks of Cancer
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Self-sufficiency in growth signals
Sustained Angiogenesis Insensitive to anti-growth factors Evasion of apoptosis Limitless replicative potential Tissue evasion and metastasis |
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Apoptosis
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Highly organized:
- internals condense and nucleus fragments - PM blebs but stays in tact. - no inflammation - triggered by pro-apoptotic stimuli (cytotoxic drugs) |
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Necrosis
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Highly disorganized:
- uncontrolled cell lysis - complete PM disruption - inflammatory response and damage to neighbours - triggered by cell injury/trauma |
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Common toxicities to cancer treatment
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1. Bone marrow supression
a) neutropenia b) thrombocytopenia 2. Gastrointestinal a) nausea and vomiting 3. Cardiotoxicity a) multiple manifestations - congestive heart failure - ischemia - coronary artery spasm 4. Hair and nails (alopecia, onycholysis) 5. Pulmonary (pneumonitis) 6. Nervous system (peripheral neuropathy) 7. Infertility 8. Secondary Cancers |
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Cyclophosphamide
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Alkylating Agent
Damages DNA by covalently adding alkyl groups to crosslink DNA |
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Cisplatin
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Platinum Comound
Crosslinks DNA and blocks replication |
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Bleomycin
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Antitumor Antibiotic
Binds DNA and Fe2+ -> Generates free radicals that damage DNA |
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Methotrexate
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Antimetabolites: Folate Analogues
Inhibits DHFR to reduce folate in cell. Blocks DNA synthesis |
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5-Fluorouracil (5-FU)
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Antimetabolites - Pyrimidine Analogue
Inhibits Thymidilate Synthase (TS) Depletes cell of thymidine Blocks DNA synthesis |
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Thioguanine
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Antimetabolites - Purine Analogues
Guanine derivative incorporates into DNA. Inhibits replication and transcription. |
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Doxorubicin
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Topoisomerase inhibitors
Stabilize topo-induced DNA strand breaks Intercalates into DNA to interfere w/ DNA synth and txn Damage by oxygen free radicals |
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Etoposide
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Topoisomerase inhibitor
Stabilize topo-induced DNA strand breaks |
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Paclitaxel
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Antimitotic agent - Taxanes
Binds microtubules and inhibits depolymerization. |
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Vincristine
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Antimitotic agent - Vinca alkaloids
Bind cytoplasmic tubulin and prevent microtubule polymerization. |
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ACT Therapy
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Doxorubicin
Cyclophosphamide Paclitaxel |
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Anastrozole
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Hormone - Aromatase inhibitors
Blocks aromatase that converts testosterone to estradiol. Prevent breast cancer. |
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Tamoxifen
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Hormone - Anti-estrogen
Compete with estrogen receptor binding. Blocks txn of growth and prolif signals. |
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Goserelin
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LHRH Analogue
Blocks testosterone production via pituitary |
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Flutamide
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Antiandrogen
Block action of testosterone in prostate cells |
