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Advanced Bioinformatics Lecture 2: Cancer pathways and therapeutics

Explore the nature of cancer and how it arises, the pathways involved in cancer development, the cell cycle clock and its role in cancer, and the molecular targets of cancer. Learn about the different stages of tumor development, the principles of cancer development, and the importance of proto-oncogenes and tumor suppressor genes. Discover the pathways involved in cancer growth regulation, apoptosis, angiogenesis, cytoskeletal signaling, immune regulation, and cell cycle control. Finally, delve into the molecular targets, specifically kinases, that are crucial in cancer therapeutics.

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Advanced Bioinformatics Lecture 2: Cancer pathways and therapeutics

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  1. Advanced Bioinformatics Lecture 2: Cancer pathways and therapeutics ZHU FENG zhufeng@cqu.edu.cn http://idrb.cqu.edu.cn/ Innovative Drug Research Centre in CQU 创新药物研究与生物信息学实验室

  2. Table of Content The nature of cancer How cancer arises Pathway involved in cancer Cell cycle clock and cancer Molecular target of cancer 2

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  6. The nature of cancer cells • Normal cells Reproduce only when instructed to do so by other cells in their vicinity. Such unceasing collaboration ensures that each tissue maintains a size and architecture appropriate to the body’s needs. • Cancer cells (in stark contrast) • become deaf to the usual controls on proliferation and follow their own internal agenda for reproduction. • possess an even more insidious ability: migrating and invading nearby tissues and forming masses at distant sites in the body. 6

  7. Tumor Development Occurs in Stages 7 Migrate & Invade

  8. Principles in cancer development • Common ancestor Cancer cells descend from a common ancestral cell, usually decades before a tumor initiates a program of inappropriate reproduction. • Accumulation of mutations The malignant transformation of a cell comes about through the accumulation of mutations in specific classes of the genes within it. • Genes playing major roles in triggering cancer Proto-oncogenes encourage growth, whereas tumor suppressor genes inhibit it. Collectively these two gene classes account for much of the uncontrolled cell proliferation seen in human cancers. 8

  9. Proto-oncogene Mutations on proto-oncogene may cause the over-production of its encoded growth stimulatory protein or an overly active form of it. Mutated proto-oncogene becomes carcinogenic oncogene that drive excessive multiplication. From proto-oncogene to oncogene 9

  10. Categories of proto-oncogene 10

  11. Tumor suppressor gene Contribute to cancer when they are inactivated by mutations. The resulting loss of functional suppressor proteins deprives the cell of crucial brakes that prevent inappropriate growth. 11

  12. p53 – tumor suppressor Inactivated by its negative regulator, mdm2 Many pathways lead to dissociation of p53-mdm2 complex Active form of p53 12

  13. Well-known oncogenes and tumor suppressors 13

  14. How cancer arises? 14

  15. Integrated circuit of the cell 15

  16. Pathways Involved in Cancer 16

  17. Pathways involved in cancer • Growth regulation (cell development, division and reproduction) • Regulation of apoptosis (process of programmed cell death) • Angiogenesis (new blood vessels form from pre-existing vessels) • Cytoskeletal signaling (cellular scaffold govern migration) • Immune regulation (defense sytem to avoid disease) • Cell cycle control (events leading to cell division and duplication) • Multiple regulation (collective effects reflect pathway complexity) 17

  18. Growth regulation MAPK/Erk in Growth and Differentiation 18

  19. Regulation of apoptosis Apoptosis regulation via mitochondria Apoptosis regulation via death receptor 19

  20. Angiogenesis Endothelial cells, which form the innermost layer of blood vessel, encircle red blood cell. Pericytes characteristically lining the outer surface of endothelial cells 20

  21. Cytoskeletal signaling, invasion and migration Regulation of Microtubule Dynamics Regulation of Actin Dynamics 21

  22. Immune regulation B Cell Receptor Signaling T Cell Receptor Signaling 22

  23. Cell cycle control G1/S Checkpoint G2/M DNA Damage Checkpoint 23

  24. Multiple regulation PI3K / Akt Signaling 24

  25. The Cell Cycle Clock and Cancer 25

  26. The Cell Cycle Clock and Cancer 26

  27. Molecular targets of cancer 27

  28. Human Protein Kinases Overview 28

  29. Molecular targets (kinases) of cancer 29

  30. Molecular targets (kinases) of cancer 30

  31. Molecular targets (kinases) of cancer 31

  32. Molecular targets (kinases) of cancer 32

  33. Molecular targets (kinases) of cancer 33

  34. Molecular targets (kinases) of cancer 34

  35. Molecular targets (kinases) of cancer 35

  36. Molecular targets (kinases) of cancer 36

  37. Molecular targets (kinases) of cancer 37

  38. Molecular targets (kinases) of cancer 38

  39. Molecular targets (kinases) of cancer 39

  40. Molecular targets (kinases) of cancer 40

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  43. Any questions? Thank you! 43

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