Presentation on theme: "Cancer—Principles and overview By Robert A. Weinberg"— Presentation transcript:
1 Cancer—Principles and overview By Robert A. Weinberg Chapter 13Cancer—Principles and overviewByRobert A. Weinberg
2 13.1 Tumors are masses of cells derived from a single cell Cancers progress from:a single mutant cellto a tumorthen to metastasisTumors are clonal.Tumors are classified by cell type.
3 13.2 Cancer cells have a number of phenotypic characteristics Cancer cells are characterized by several distinct properties.Unlike normal cells, cancer cells do not stop dividing when they contact a neighboring cell when such cells are propagated in a Petri dish.
4 13.2 Cancer cells have a number of phenotypic characteristics Cancer cells have a greatly reduced requirement for growth factors to sustain growth and proliferation.Unlike normal cells, cancer cells in culture do not require attachment to a physical substrate in order to grow.The trait of anchorage independence
5 13.2 Cancer cells have a number of phenotypic characteristics Unlike normal cells in culture, which halt division after a certain number of growth-and-division cycles:cancer cells are immortalthey do not stop dividing after a predetermined number of generationsCancer cells often have chromosomal aberrations, including changes in chromosome number and structure.
6 13.3 Cancer cells arise after DNA damage Agents that cause cancer may do so by damaging DNA.Mutations in certain genes cause a cell to grow abnormally.
7 Cancers usually arise in somatic cells. 13.3 Cancer cells arise after DNA damageAmes devised a test to determine the carcinogenicity of chemical agents.Cancers usually arise in somatic cells.
8 13.4 Cancer cells are created when certain genes are mutated Oncogenes promote cell growth and division.Tumor suppressors inhibit cell growth and division.
9 Cellular genomes harbor multiple proto-oncogenes. 13.4 Cancer cells are created when certain genes are mutatedCellular genomes harbor multiple proto-oncogenes.Tumor viruses carry oncogenes.Genetic alterations can convert proto-oncogenes into potent oncogenes.
10 13.5 Cellular genomes harbor a number of protooncogenes Gain-of-function mutations can activate protooncogenes.Overexpression of proto-oncogenes can cause tumors.Translocations can create hybrid proteins that are oncogenic.
11 13.6 Elimination of tumor suppressor activity requires two mutations Both copies of a tumor suppressor gene must usually be inactivated to see a phenotype.
12 13.6 Elimination of tumor suppressor activity requires two mutations Mechanisms that result in loss-of-heterozygosity are often responsible for the loss of the remaining normal copy of the tumor suppressor gene.Cancer susceptibility can be caused by the inheritance of a mutant copy of a tumor suppressor gene.
13 13.7 The genesis of tumors is a complex process Cancer is a multistep process that requires four to six different mutations to reach the tumor state.Tumorigenesis progresses by clonal expansion, where increasingly abnormal clones of cells outgrow their less mutant neighbors.
14 13.8 Cell growth and proliferation are activated by growth factors Cell signaling requires extracellular factors, receptors, and other proteins that transmit the signal to the nucleus.
15 Extracellular signals may be: 13.8 Cell growth and proliferation are activated by growth factorsExtracellular signals may be:growth promoting orgrowth inhibitingMany genes encoding cell signaling molecules are proto-oncogenes and tumor suppressor genes.
16 13.9 Cells are subject to growth inhibition and may exit from the cell cycle Cells that have differentiated have reached their final specialized form.Differentiated cells are usually postmitotic.Thus, differentiation reduces the pool of dividing cells.
17 Cells can commit suicide by apoptosis. 13.9 Cells are subject to growth inhibition and may exit from the cell cycleCells can commit suicide by apoptosis.Apoptosis eliminates healthy cells during development and at other times in an organism’s lifetime.
18 13.9 Cells are subject to growth inhibition and may exit from the cell cycle Apoptosis eliminates damaged cells that can pose a threat to the organism.Mutations that compromise a cell’s ability to carry out apoptosis can result in malignancy.
19 13.10 Tumor suppressors block inappropriate entry into the cell cycle Cells decide whether or not to divide at the restriction point.pRb is a tumor suppressor that can prevent passage through the restriction point.
20 pRb can be inactivated by: 13.10 Tumor suppressors block inappropriate entry into the cell cyclepRb can be inactivated by:mutationssequestration by oncoproteinshyperactivity of the Ras pathway
21 13.11 Mutation of DNA repair and maintenance genes can increase the overall mutation rate DNA repair proteins keep the spontaneous mutation rate low.Defects in DNA repair genes increase the basal rate of mutation in the cell.Mutations in checkpoint proteins compromise chromosome integrity.
22 13.12 Cancer cells may achieve immortality Cancer cells avoid senescence by inactivating tumor suppressor genes.Cancer cells reach a crisis point at which many of them die off.
23 Cells that survive the crisis are immortalized. 13.12 Cancer cells may achieve immortalityCells that survive the crisis are immortalized.Telomeres become shorter each generation unless telomerase is activated.
24 13.12 Cancer cells may achieve immortality When telomeres become too short to protect the chromosomes, the chromosomes fuse.This provokes crisis.Most cancer cells activate telomerase transcription, thereby escaping death.
25 13.13 Access to vital supplies is provided by angiogenesis Tumor growth is limited by access to nutrients and waste removal mechanisms.Tumors can stimulate blood vessel growth (angiogenesis), which enables them to expand.
26 13.14 Cancer cells may invade new locations in the body Some cells from a primary tumor can gain entrance to blood and lymphatic vessels (intravasation).The process of intravasation often requires breaking through barriers of neighboring tissue.
27 13.14 Cancer cells may invade new locations in the body Cells that survive the trip through the blood vessels may colonize other organs.Metastasis, or colonization of other tissues, usually results in death of the individual.