1. Cancer

2. Tumors arise from normal tissues Tumors are created by cells that have lost the ability to assemble and create tissues of normal form and function

4. Depending on the degree of aggressive growth – tumors can be classified as benign (grow locally without invading adjacent tissues) or malignant (invade nearby tissues and spawn metastases)

11. Most tumors are derived from a single abnormal cell

12. Cancer cells contain somatic mutations

23. A single mutation is not enough to cause cancer

24. Cancers develop gradually from increasingly aberrant cells

27. Tumor progression involves successive rounds of random inherited change followed by natural selection

28. Cancer cells undergo epigenetic and genetic changes

29. A small population of cancer stem cells maintains many tumors

30. Metastasis is the cause of 90% of deaths from solid tumors

32. Primary tumors and their metastatic tropisms

33. Characteristic features of metastasis – steps in a cascade - loss of cellular adhesion - increased motility and invasiveness - entry and survival in the circulation - exit into new tissue - eventual colonization of a distant site

34. Steps in the process of metastasis

36. Travel of cancer cells from a primary tumor site to a site of potential metastasis depends on a series of complex biological steps The invasion-metastasis cascade

37. Mutations that lead to metastasis are still a mystery Barriers to metastasis

38. Colonization represents the most complex and challenging step of the invasion-metastasis cascade Steps leading to extravasation

39. The epithelial-mesenchymal transition (EMT) and associated loss of E-cadherin expression enable carcinoma cells to become invasive

41. The tumor microenvironment influences cancer development

42. The epithelial-mesenchymal transition (EMT) is often induced by stromal cells

48. COX2 – prostaglandin-synthesizing enzyme (cyclooxgenase-2) – promotes extravasation in the lungs; prostaglandin production during inflammation increases blood-brain barrier permeability HBEGF – Heparin-binding EGF – EGFR ligand – induces cancer cell motility and invasiveness ST6GALNAC5 –  2,6-sialyltransferase – catalyses the addition of sialic acid to gangliosides and glycoproteins; makes cell more adhesive and mediates infiltration into the brain