Cancer and metastasis – Flashcards
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Cancer
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a microevolutionary process where individual mutant clones begin by prospering at expense of neighbors. They reproduce in defiance of normal restraints and invade and colonize other tissues.
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Clonal origin
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evidence from lack of X c-some mosaicism in females.
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Cancer progression
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includes three basic parameters—mutation rate, number of cells reproducing and rate of reproduction.
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Cancer stem cell hypothesis
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a population of rare self-renewing "stem cells" maintain tumor and are responsible for metastasis.
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Oncogenes
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have a gain of function. Examples are myc, ras, src.
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Tumor suppressor genes
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loss of function. Need both copies gone. Examples are Rb, p53, PTEN.
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PI3 kinase/Akt pathway
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often abnormally activated in cancer cells because they are dependent on glycolysis and have abnormal metabolism.
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P53
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tumor suppressor gene mutated in about half of all cancers. Important prognostic tool for cancer. Rb and p53 are targets for viral oncoproteins like human papilloma virus.
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Rb
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tumor suppressor gene. Inhibits E2F which launches cell into S phase. It is inhibited by cyclin D Cdk4 complex which is in turn inhibited by p16.
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Ionizing radiation
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used to kill cancer cells. Damage can induce p53 if it is present causing apoptosis or be sufficient enough to cause mitotic failure and cell death.
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Chemotherapy
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used to treat cancer. Can damage DNA or arrest mitosis.
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Anit-angiogenesis drugs
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arrest vascularsation of tumors causing death. Eg Bevacizumab.
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Gleevec
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used to treat chronic myelogenous leukemia. The Philadelphia c-some causes bcr and abl to fuse and form active deleterious kinase. The drug inhibits this kinase specifically.
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Loco-regional metastasis
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nearby extension from primary organ and spread to draining lymp nodes.
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Distant metastasis
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hematogenous dissemination of cancer cells.
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Metastasis assessments
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include histopathology from primary tumor biopsy, detection of metastasis to regional lymph nodes, biomarkers, diagnostic imaging and clinical signs.
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Metastatic cascade
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process from which primary tumor cells travel to and proliferate and secondary site. Angiogenesis, lymphangiogenesis, invasion and intravastation, travel through circulatory system, lodgement in capillary bed, extravastation, survival and growth at secondary site and angiogenesis.
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Anti vascular endothelial growth factor (VEGF)
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first approved drug to interfere with angiogenesis.
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Invasive cancer cells
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lose normal cell-cell contacts (E-cadherin), have altered adhesion to ECM (integrins), have enhanced motility and secrete ECM degrading enzymes.
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Matrix metalloproteases
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degrading Enzymes that destroy ECM and are secreted in high amounts by invasive cancer cells.
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Epithelial mesenchymal transition EMT
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normally occurs in development when epithelial cells change cadherins and move. In cancer cells happens by mutations (rare) or epigenetic events (more common).
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Metastatic inefficiency
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only a tiny fraction of cells shed into circulation may produce a clinically detectable metasis. A tumor may shed millions to billions of cells into circulation daily but shear forces and immune system destroy most.
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Dormancy
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some cancer cells are dormant after lodgement and extravastation for a period. This may be due to immune system.
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Survival and growth at secondary site
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reciprocal signaling between cancer cells and new environment may create 'vicious cycle' promoting tumor growth.
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Organ site specific metastasis
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some cancers show preference to metastasize in specific locations. May be due to blood flow, biological interactions or both. Seed and soil hypothesis.
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Genetics of metastasis
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any step may be rate limiting and cells from primary tumor have varying fitness for each step. Could lead to clonal selection. Alternatively some cancers may be destined for metastasis from early on in development due to specific mutations.
