The Multistep Nature of Cancer




                                   Karobi Moitra (Ph.D)
                               ...
Clonal Expansion in Cancer




Peter Nowell (1976) hypothesized the clonal evolution of tumors
where a tumor arises initia...
Multistep Genetic damage leads to Cancer
Multistep Genetic damage leads to Cancer
Normal cells evolve into cells with increasingly
neoplastic phenotypes through a process called
              Tumor Progre...
Normal to Invasive


         Excessive growth   Loss of cellular structure    Excessive growth     Invades
              ...
Carcinoma-in -situ




                                                             PIN = prostate intraepithelial neoplas...
Phenotype
      (observable
      characteristics)
       of
      Multistep nature
      Of cancer



                   ...
Genetic changes in Multistep Tumorigenesis
                    Adenomatous Polyposis Coli (Colon cancer)




    Note: DNA...
Darwinian Evolution and clonal succession:
                                 Natural selection




                        ...
Experimental evidence to support
 The Multistep Nature of Cancer
Oncogenes collaborate to cause cancer:
                           Experiment in rat embryo cells




Figure 11.23 The Biol...
Table 11.1 The Biology of Cancer (© Garland Science 2007)
Oncogenic collaboration
                                                                    in transgenic mice


         ...
Mice carrying both
                                                                        myc + ras have
                ...
The intracellular signaling circuitry and collaboration between cancer-
                                       associated ...
The process of tumor formation is complex and involves
                    multiple steps

  The complexity of this proces...
Boc Lecture 3 the multistep nature of cancer, Karobi Moitra
Boc Lecture 3 the multistep nature of cancer, Karobi Moitra
Boc Lecture 3 the multistep nature of cancer, Karobi Moitra
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Boc Lecture 3 the multistep nature of cancer, Karobi Moitra

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Boc Lecture 3 the multistep nature of cancer, Karobi Moitra

  1. 1. The Multistep Nature of Cancer Karobi Moitra (Ph.D) NCI Frederick , NIH Chapter 11: Cancer Inflammation Program Multi-Step Tumorigenesis Human Genetics Section Frederick MD. Copyright © Garland Science 2007
  2. 2. Clonal Expansion in Cancer Peter Nowell (1976) hypothesized the clonal evolution of tumors where a tumor arises initially from 1 specific cell which then develops a growth advantage over other cells.
  3. 3. Multistep Genetic damage leads to Cancer
  4. 4. Multistep Genetic damage leads to Cancer
  5. 5. Normal cells evolve into cells with increasingly neoplastic phenotypes through a process called Tumor Progression
  6. 6. Normal to Invasive Excessive growth Loss of cellular structure Excessive growth Invades & tissue arrangement in place Normal Hyperplasia Mild Carcinoma in dysplasia situ (severe dysplasia) Cancer (invasive)
  7. 7. Carcinoma-in -situ PIN = prostate intraepithelial neoplasia CIN = cervical intraepithelial neoplasia Leukoplakia = white patches of keratin (precancerous). Figure 11.7 The Biology of Cancer (© Garland Science 2007)
  8. 8. Phenotype (observable characteristics) of Multistep nature Of cancer Villus Crypt Adenoma = tumor of glandular origin Figure 11.6 The Biology of Cancer (© Garland Science 2007)
  9. 9. Genetic changes in Multistep Tumorigenesis Adenomatous Polyposis Coli (Colon cancer) Note: DNA hypomethylation means undermethylation, it’s role in cancer is not clearly understood. 18q TSG = DCC- deleted in colorectal cancer Figure 11.10 The Biology of Cancer (© Garland Science 2007)
  10. 10. Darwinian Evolution and clonal succession: Natural selection Growth advantage Figure 11.12 The Biology of Cancer (© Garland Science 2007)
  11. 11. Experimental evidence to support The Multistep Nature of Cancer
  12. 12. Oncogenes collaborate to cause cancer: Experiment in rat embryo cells Figure 11.23 The Biology of Cancer (© Garland Science 2007)
  13. 13. Table 11.1 The Biology of Cancer (© Garland Science 2007)
  14. 14. Oncogenic collaboration in transgenic mice Mice were created that either bore the MMTV-ras(mouse mammary tumor virus) or MMTV-myc transgene.Mice were crossbred to create double transgenic mice (with both transgenes) and their tumor free survival followed over many months. Figure 11.24a The Biology of Cancer (© Garland Science 2007)
  15. 15. Mice carrying both myc + ras have less days of tumor-free survival T50 = no. of days required for half of the mice to develop detectable mammary carcinoma Figure 11.24b The Biology of Cancer (© Garland Science 2007)
  16. 16. The intracellular signaling circuitry and collaboration between cancer- associated genes Figure 11.44 The Biology of Cancer (© Garland Science 2007)
  17. 17. The process of tumor formation is complex and involves multiple steps The complexity of this process is reflected in the long time periods required for most human cancers to develop These changes involve both the activation of oncogenes and the inactivation of tumor suppressor genes
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