2. The Cell Cycle and Mitosis

3. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Going from egg to baby…. the original fertilized egg has to divide… and divide… Getting from little to big…

4. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings For reproduction – asexual reproduction one-celled organisms For growth – from fertilized egg to multi-celled organism For repair & renewal – replace cells that die from normal wear & tear or from injury Why do cells divide? amoeba

5. Concept 12.1: Cell division results in genetically identical daughter cells Cell division requires the distribution of identical genetic material—DNA—to two daughter cells. What is remarkable is the fidelity with which DNA is passed along, without dilution, from one generation to the next. A dividing cell duplicates its DNA, allocates the two copies to opposite ends of the cell, and then splits into two daughter cells. A cell’s genetic information, packaged as DNA, is called its genome. – In prokaryotes, the genome is often a single long DNA molecule. – In eukaryotes, the genome consists of several DNA molecules.

6. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Getting the right stuff What is passed on to daughter cells? – exact copy of genetic material = DNA mitosis – organelles, cytoplasm, cell membrane, enzymes cytokinesis chromosomes (stained orange) in kangaroo rat epithelial cell  notice cytoskeleton fibers

7. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Overview of mitosis interphaseprophase(pro-metaphase) metaphaseanaphasetelophase cytokinesis I.P.M.A.T.

8. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Organizing DNA DNA is organized in chromosomes – double helix DNA molecule – wrapped around histone proteins like thread on spools – DNA-protein complex = chromatin organized into long thin fiber – condensed further during mitosis DNA histones chromatin duplicated mitotic chromosome ACTGGTCAGGCAATGTC double stranded chromosome

9. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Copying DNA & packaging it… After DNA duplication, chromatin condenses – coiling & folding to make a smaller package DNA chromatin mitotic chromosome

10. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings double- stranded mitotic human chromosomes

11. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Mitotic Chromosome Duplicated chromosome – 2 sister chromatids – narrow at centromeres – contain identical copies of original DNA homologous chromosomes homologous chromosomes sister chromatids homologous = “same information” single-stranded double-stranded

12. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Interphase 90% of cell life cycle – cell doing its “everyday job” produce RNA, synthesize proteins/enzymes – prepares for duplication if triggered I’m working here! Time to divide & multiply!

13. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Cell cycle Cell has a “life cycle” cell is formed from a mitotic division cell grows & matures to divide again cell grows & matures to never divide again G 1, S, G 2, M G1G0G1G0 epithelial cells, blood cells, stem cells liver cells brain / nerve cells muscle cells

14. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Interphase Divided into 3 phases: – G 1 = 1 st Gap (Growth) cell doing its “everyday job” cell grows – S = DNA Synthesis copies chromosomes – G 2 = 2 nd Gap (Growth) prepares for division cell grows (more) produces organelles, proteins, membranes G0G0 signal to divide

15. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Interphase Nucleus well-defined – DNA loosely packed in long chromatin fibers Prepares for mitosis – replicates chromosome DNA & proteins – produces proteins & organelles green = key features

16. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Synthesis phase of Interphase – dividing cell replicates DNA – must separate DNA copies correctly to 2 daughter cells human cell duplicates ~3 meters DNA each daughter cell gets complete identical copy error rate = ~1 per 100 million bases – 3 billion base pairs in mammalian genome – ~30 errors per cell cycle mutations (to somatic (body) cells) S phase: Copying / Replicating DNA

17. A typical human cell might divide once every 24 hours. – Of this time, the M phase would last less than an hour, while the S phase might take 10–12 hours, or half the cycle. – The rest of the time would be divided between the G1 and G2 phases. – The G1 phase varies most in length from cell to cell.

18. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Mitosis Dividing cell’s DNA between 2 daughter nuclei – “dance of the chromosomes” 4 phases – prophase – metaphase – anaphase – telophase

19. LE 12-6ca G 2 OF INTERPHASE PROPHASEPROMETAPHASE

20. LE 12-6da METAPHASEANAPHASE TELOPHASE AND CYTOKINESIS 10 µm

21. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Prophase Chromatin condenses – visible chromosomes chromatids Centrioles move to opposite poles of cell – animal cell Protein fibers cross cell to form mitotic spindle composed of centrosomes and the microtubules that extend from them – microtubules actin, myosin – The radial arrays of shorter microtubules that extend from the centrosomes are called asters – coordinates movement of chromosomes Nucleolus disappears Nuclear membrane breaks down green = key features

22. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Transition to Metaphase Prometaphase – spindle fibers attach to centromeres creating kinetochores – microtubules attach at kinetochores connect centromeres to centrioles – chromosomes begin moving green = key features

23. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Metaphase Chromosomes align along middle of cell – metaphase plate meta = middle – spindle fibers coordinate movement – helps to ensure chromosomes separate properly so each new nucleus receives only 1 copy of each chromosome green = key features

24. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

25. Anaphase Sister chromatids separate at kinetochores – move to opposite poles – pulled at centromeres – pulled by motor proteins “walking”along microtubules actin, myosin increased production of ATP by mitochondria Poles move farther apart – polar microtubules lengthen green = key features

26. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Separation of chromatids In anaphase, proteins holding together sister chromatids are inactivated – separate to become individual chromosomes – By the end, the two poles have equivalent collections of chromosomes 2 chromosomes 1 chromosome 2 chromatids single-stranded double-stranded

27. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Telophase Chromosomes arrive at opposite poles – daughter nuclei form – nucleoli form – chromosomes disperse no longer visible under light microscope Spindle fibers disperse Cytokinesis begins – cell division green = key features

28. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Cytokinesis Animals – constriction belt of actin microfilaments around equator of cell cleavage furrow forms splits cell in two like tightening a draw string

29. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Cytokinesis in Plants Plants – cell plate forms vesicles line up at equator – derived from Golgi vesicles fuse to form 2 cell membranes – new cell wall laid down between membranes new cell wall fuses with existing cell wall

30. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Cytokinesis in plant cell

31. LE 12-9a Cleavage furrow 100 µm Contractile ring of microfilaments Daughter cells Cleavage of an animal cell (SEM)

32. LE 12-9b 1 µm Daughter cells Cell plate formation in a plant cell (TEM) New cell wall Cell plate Wall of parent cell Vesicles forming cell plate

33. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Kinetochores use motor proteins that “walk” chromosome along attached microtubule – microtubule shortens by dismantling at kinetochore (chromosome) end Chromosome movement

34. What is the function of the nonkinetochore microtubules? Nonkinetochore microtubules are responsible for lengthening the cell along the axis defined by the poles. – These microtubules interdigitate and overlap across the metaphase plate. – During anaphase, the area of overlap is reduced as motor proteins attached to the microtubules walk them away from one another, using energy from ATP. – As microtubules push apart, the microtubules lengthen by the addition of new tubulin monomers to their overlapping ends, allowing continued overlap.

35. LE 12-10 Nucleus Cell plate Chromosomes Nucleolus Chromatin condensing 10 µm Prophase. The chromatin is condensing. The nucleolus is beginning to disappear. Although not yet visible in the micrograph, the mitotic spindle is starting to form. Prometaphase. We now see discrete chromosomes; each consists of two identical sister chromatids. Later in prometaphase, the nuclear envelope will fragment. Metaphase. The spindle is complete, and the chromosomes, attached to microtubules at their kinetochores, are all at the metaphase plate. Anaphase. The chromatids of each chromosome have separated, and the daughter chromosomes are moving to the ends of the cell as their kinetochore micro- tubules shorten. Telophase. Daughter nuclei are forming. Meanwhile, cytokinesis has started: The cell plate, which will divide the cytoplasm in two, is growing toward the perimeter of the parent cell.

36. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Mitosis in whitefish blastula

37. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Mitosis in animal cells

38. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Mitosis in plant cell

39. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings onion root tip

40. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Origin of replication chromosome: double-stranded DNA replication of DNA elongation of cell cell pinches in two ring of proteins Evolution of mitosis Mitosis in eukaryotes likely evolved from binary fission in bacteria – single circular chromosome – no membrane- bound organelles

41. LE 12-11_3 Origin of replication Cell wall Plasma membrane Bacterial chromosome E. coli cell Two copies of origin Chromosome replication begins. Soon thereafter, one copy of the origin moves rapidly toward the other end of the cell. Replication continues. One copy of the origin is now at each end of the cell. Origin Replication finishes. The plasma membrane grows inward, and new cell wall is deposited. Two daughter cells result. Cell elongates

42. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Evolution of mitosis A possible progression of mechanisms intermediate between binary fission & mitosis seen in modern organisms protists dinoflagellates protists diatoms eukaryotes yeast eukaryotes animals prokaryotes (bacteria)

43. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Coordination of cell division A multicellular organism needs to coordinate cell division across different tissues & organs – critical for normal growth, development & maintenance coordinate timing of cell division coordinate rates of cell division not all cells can have the same cell cycle

44. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings G2G2 S G1G1 M metaphase prophase anaphase telophase interphase (G 1, S, G 2 phases) mitosis (M) cytokinesis (C) C Frequency of cell division varies by cell type – embryo cell cycle < 20 minute – skin cells divide frequently throughout life 12-24 hours cycle – liver cells retain ability to divide, but keep it in reserve divide once every year or two – mature nerve cells & muscle cells do not divide at all after maturity permanently in G 0 Frequency of cell division

45. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Watch These make Notes on Them http://www.youtube.com/watch?v=2aVnN4RePyI http://www.youtube.com/watch?v=L0k-enzoeOM http://highered.mcgraw- hill.com/sites/0072495855/student_view0/chapter2 /animation__how_the_cell_cycle_works.htmlhttp://highered.mcgraw- hill.com/sites/0072495855/student_view0/chapter2 /animation__how_the_cell_cycle_works.html https://highered.mcgraw- hill.com/sites/0072495855/student_view0/chapter2 /animation__control_of_the_cell_cycle.htmlhttps://highered.mcgraw- hill.com/sites/0072495855/student_view0/chapter2 /animation__control_of_the_cell_cycle.html http://www.mhhe.com/biosci/bio_animations/06_M H_CellCycle_Web/index.htmlhttp://www.mhhe.com/biosci/bio_animations/06_M H_CellCycle_Web/index.html

46. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Overview of Cell Cycle Control Two irreversible points in cell cycle – replication of genetic material – separation of sister chromatids Checkpoints – process is assessed & possibly halted centromere sister chromatids single-stranded chromosomes double-stranded chromosomes There ’ s no turning back, now!

47. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Checkpoint control system Checkpoints – cell cycle controlled by STOP & GO chemical signals at critical points – signals indicate if key cellular processes have been completed correctly

48. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Checkpoint control system 3 major checkpoints: – G 1 /S can DNA synthesis begin? – G 2 /M has DNA synthesis been completed correctly? commitment to mitosis – spindle checkpoint are all chromosomes attached to spindle? can sister chromatids separate correctly?

49. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings G 1 /S checkpoint G 1 /S checkpoint is most critical – primary decision point “restriction point” – if cell receives “GO” signal, it divides internal signals: cell growth (size), cell nutrition external signals: “growth factors” – if cell does not receive signal, it exits cycle & switches to G 0 phase non-dividing, working state

50. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings G 0 phase – non-dividing, differentiated state – most human cells in G 0 phase  liver cells  in G 0, but can be “called back” to cell cycle by external cues  nerve & muscle cells  highly specialized  arrested in G 0 & can never divide

51. LE 12-14 G 1 checkpoint G1G1 S M M checkpoint G 2 checkpoint G2G2 Control system

52. LE 12-15 G1G1 G 1 checkpoint G1G1 G0G0 If a cell receives a go-ahead signal at the G 1 checkpoint, the cell continues on in the cell cycle. If a cell does not receive a go-ahead signal at the G 1 checkpoint, the cell exits the cell cycle and goes into G 0, a nondividing state.

53. LE 12-16b Degraded cyclin G 2 checkpoint S M G2G2 G1G1 Cdk Cyclin is degraded MPF Cyclin Cdk Molecular mechanisms that help regulate the cell cycle accumulation Cyclin Synthesis of Cyclin begins in late S phase and continues through G2. Cyclin in protected from degradation so it accumulates. Cyclin molecules combine with recycled Cdk, producing enough molecules of MPF and cell passes to G2 checkpoint MPF = M- phase promoting factor MPF peaks during metaphase. MPF promotes mitosis. Anaphase – Cyclin component of MPF is degraded, terminating M phase. G1, cyclin degradation and Cdk component of MPF is recycled.

54. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings How do cells know when to divide? – cell communication signals chemical signals in cytoplasm give cue signals usually mean proteins – activators – inhibitors Activation of cell division experimental evidence: Can you explain this?

55. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings “Go-ahead” signals Protein signals that promote cell growth & division – internal signals “promoting factors” – external signals “growth factors” Primary mechanism of control – phosphorylation kinase enzymes either activates or inactivates cell signals

56. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Cell cycle s ignals Cell cycle controls – cyclins regulatory proteins levels cycle in the cell – Cdks cyclin-dependent kinases phosphorylates cellular proteins – activates or inactivates proteins – Cdk-cyclin complex triggers passage through different stages of cell cycle activated Cdk inactivated Cdk

57. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Cdk / G 1 cyclin Cdk / G 2 cyclin (MPF) G2G2 S G1G1 C M G 2 / M checkpoint G 1 / S checkpoint APC Active Inactive Active Inactive Active mitosis cytokinesis MPF = Mitosis Promoting Factor APC = Anaphase Promoting Complex Replication completed DNA integrity Chromosomes attached at metaphase plate Spindle checkpoint Growth factors Nutritional state of cell Size of cell

58. MPF (“maturation-promoting factor” or “M-phase- promoting-factor”) triggers the cell’s passage past the G2 checkpoint to the M phase. – MPF promotes mitosis by phosphorylating a variety of other protein kinases. – MPF stimulates fragmentation of the nuclear envelope by phosphorylation of various proteins of the nuclear lamina. – It also triggers the breakdown of cyclin, dropping cyclin and MPF levels during mitosis and inactivating MPF. The noncyclin part of MPF, the Cdk, persists in the cell in inactive form until it associates with new cyclin molecules synthesized during the S and G2 phases of the next round of the cycle.

59. LE 12-16a MPF activity G1G1 G2G2 S MS M G2G2 G1G1 M Cyclin Time Fluctuation of MPF activity and cyclin concentration during the cell cycle Relative concentration

60. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Cyclin & Cyclin-dependent kinases CDKs & cyclin drive cell from one phase to next in cell cycle  proper regulation of cell cycle is so key to life that the genes for these regulatory proteins have been highly conserved through evolution  the genes are basically the same in yeast, insects, plants & animals (including humans)

61. Internal and external cues help regulate the cell cycle. While research scientists know that active Cdks function by phosphorylating proteins, the identity of all these proteins is still under investigation. Scientists do not yet know what Cdks actually do in most cases. Some steps in the signaling pathways that regulate the cell cycle are clear. – Some signals originate inside the cell, others outside.

62. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings External signals Growth factors – coordination between cells – protein signals released by body cells that stimulate other cells to divide density-dependent inhibition – crowded cells stop dividing – each cell binds a bit of growth factor not enough activator left to trigger division in any one cell anchorage dependence – to divide cells must be attached to a substrate “touch sensor” receptors

63. Particularly important for mammalian cells are growth factors, proteins released by one group of cells that stimulate other cells to divide. – For example, platelet-derived growth factors (PDGF), produced by platelet blood cells, bind to tyrosine-kinase receptors of fibroblasts, a type of connective tissue cell. – This triggers a signal-transduction pathway that allows cells to pass the G1 checkpoint and divide. Each cell type probably responds specifically to a certain growth factor or combination of factors.

64. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings E2F nucleus cytoplasm cell division nuclear membrane growth factor protein kinase cascade nuclear pore chromosome Cdk cell surface receptor P P P P P E2F Rb Growth factor signals

65. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Example of a Growth Factor Platelet Derived Growth Factor (PDGF) – made by platelets in blood clots – binding of PDGF to cell receptors stimulates cell division in connective tissue heal wounds Don’t forget to mention erythropoietin! (EPO)

66. The role of PDGF is easily seen in cell culture. – Fibroblasts in culture will only divide in the presence of a medium that also contains PDGF. In a living organism, platelets release PDGF in the vicinity of an injury. – The resulting proliferation of fibroblasts helps heal the wound. At least 50 different growth factors can trigger specific cells to divide.

67. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Growth Factors and Cancer Growth factors can create cancers – proto-oncogenes normally activates cell division – growth factor genes – become oncogenes (cancer-causing) when mutated if switched “ON” can cause cancer example: RAS (activates cyclins) – tumor-suppressor genes normally inhibits cell division if switched “OFF” can cause cancer example: p53

68. The abnormal behavior of cancer cells begins when a single cell in a tissue undergoes a transformation that converts it from a normal cell to a cancer cell. – Normally, the immune system recognizes and destroys transformed cells. – However, cells that evade destruction proliferate to form a tumor, a mass of abnormal cells.

69. LE 12-18b Cancer cells do not exhibit anchorage dependence or density-dependent inhibition. Cancer cells 25 µm

70. Cancer cells have escaped from cell cycle controls. Cancer cells divide excessively and invade other tissues because they are free of the body’s control mechanisms. – Cancer cells do not stop dividing when growth factors are depleted. – This is either because a cancer cell manufactures its own growth factors, has an abnormality in the signaling pathway, or has an abnormal cell cycle control system. If and when cancer cells stop dividing, they do so at random points, not at the normal checkpoints in the cell cycle.

71. Cancer cells may divide indefinitely if they have a continual supply of nutrients. – In contrast, nearly all mammalian cells divide 20 to 50 times under culture conditions before they stop, age, and die. Cancer cells may be “immortal.” – HeLa cells from a tumor removed from a woman (Henrietta Lacks) in 1951 are still reproducing in culture.

72. In addition to chromosomal and metabolic abnormalities, cancer cells often lose attachment to nearby cells, are carried by the blood and lymph system to other tissues, and start more tumors in an event called metastasis. – Cancer cells are abnormal in many ways. – They may have an unusual number of chromosomes, their metabolism may be disabled, and they may cease to function in any constructive way. – Cancer cells may secrete signal molecules that cause blood vessels to grow toward the tumor.

73. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Cancer & Cell Growth Cancer is essentially a failure of cell division control – unrestrained, uncontrolled cell growth What control is lost? – lose checkpoint stops – gene p53 plays a key role in G 1 /S restriction point p53 protein halts cell division if it detects damaged DNA – options: stimulates repair enzymes to fix DNA forces cell into G 0 resting stage keeps cell in G 1 arrest causes apoptosis of damaged cell ALL cancers have to shut down p53 activity p53 discovered at Stony Brook by Dr. Arnold Levine p53 is the Cell Cycle Enforcer

74. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings DNA damage is caused by heat, radiation, or chemicals. p53 allows cells with repaired DNA to divide. Step 1 DNA damage is caused by heat, radiation, or chemicals. Step 1 Step 2 Damaged cells continue to divide. If other damage accumulates, the cell can turn cancerous. Step 3 p53 triggers the destruction of cells damaged beyond repair. ABNORMAL p53 NORMAL p53 abnormal p53 protein cancer cell Step 3 The p53 protein fails to stop cell division and repair DNA. Cell divides without repair to damaged DNA. Cell division stops, and p53 triggers enzymes to repair damaged region. Step 2 DNA repair enzyme p53 protein p53 protein p53 — master regulator gene

75. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Development of Cancer Cancer develops only after a cell experiences ~6 key mutations (“hits”) – unlimited growth turn on growth promoter genes – ignore checkpoints turn off tumor suppressor genes (p53) – escape apoptosis turn off suicide genes – immortality = unlimited divisions turn on chromosome maintenance genes – promotes blood vessel growth turn on blood vessel growth genes – overcome anchor & density dependence turn off touch-sensor gene It ’ s like an out-of-control car with many systems failing!

76. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings What causes these “hits”? Mutations in cells can be triggered by – UV radiation – chemical exposure – radiation exposure – heat – cigarette smoke – pollution – age – genetics

77. LE 12-19 Cancer cell Blood vessel Lymph vessel Tumor Glandular tissue Metastatic tumor A tumor grows from a single cancer cell. Cancer cells invade neighboring tissue. Cancer cells spread through lymph and blood vessels to other parts of the body. A small percentage of cancer cells may survive and establish a new tumor in another part of the body.

78. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Tumors Mass of abnormal cells – Benign tumor abnormal cells remain at original site as a lump – p53 has halted cell divisions most do not cause serious problems & can be removed by surgery – Malignant tumor cells leave original site – lose attachment to nearby cells – carried by blood & lymph system to other tissues – start more tumors = metastasis impair functions of organs throughout body

79. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Traditional treatments for cancers Treatments target rapidly dividing cells – high-energy radiation kills rapidly dividing cells – chemotherapy stop DNA replication stop mitosis & cytokinesis stop blood vessel growth

80. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings New “miracle drugs” Drugs targeting proteins (enzymes) found only in cancer cells – Gleevec treatment for adult leukemia (CML) & stomach cancer (GIST) 1st successful drug targeting only cancer cells Novartes without Gleevec with Gleevec