Biology of Cancer:

1. Biology of Cancer: What effect does cancer have on the patient?

2. DISEASE BURDEN • Second only to heart disease as a cause of death Causes much human suffering • Cancer results from damage to DNA which can either be acquired or inherited • All cancers are not the same it is not a single disease • The outcome and prognosis of the cancer • Depends on the cell type and origin • The tissue of origin

4. Hereditary Breast Cancer

5. The type of cancer cell will have a big impact on treatment modalities • iesurgery versus chemotherapy versus no treatment • The progression of the cancer depends on the cell type in which the cancer arose. • Some cancers are more slow growing and less likely to spread than others

7. Characteristics of Cancer cells • 1. Reproduce despite normal constraints that inhibit cell proliferation and clonal expansion -ie a cancer cell loses control over the cell cycle and cell division Normally a cell only divides following stimulation by growth factors or hormones • 2. Cancer cells invade and colonize territories normally reserved for other cells

8. Cancer : Unregulated Cell Growth • Autonomous/deregulated cell growth defining feature of all cancers (neoplasms) • Deregulated cell growth not necessarily due to increased cell proliferation - critical balance between Cell division ( cell cycle progression- cell proliferation) Apoptosis (Cell Death)

9. Cancer is caused by the accumulation of genetic alterations that confer a survival advantage to the cancer cell • • Changes may result in: • -increased cell growth • -resistance to apoptosis • -altered tissue invasiveness • -angiogenicproliferation • (formation of new blood vessels) • -ability to escape immune surveillance

10. CANCER IS CLONAL • Genetic nature of cancer is reflected in the clonalnature of the cancer cells • i.e. daughter cells inherit the properties of the mother cell • • Recognition that cancer is a genetic disease has lead to intensive effort to characterize genes responsible which has lead to new therapies

11. The change from a normal cell to a cancer cell is called cell transformation • Cancer cells don’t look like normal cells • The pathologist uses the change in the appearance of the cell to diagnose the cancer

12. Cancer cells show – enlarged nucleus, changes to the cytoskeleton, loss of specialized features • There is a spectrum in the changes in appearance of the cancer cell • With some highly malignant cancers it is impossible to tell the cell of origin • Much data to suggest as a cancer develops there is the accumulation of genetic errors and increasing change in cell appearance

13. Photographs of cells collected by scraping the surface of the uterinecervix (the Papanicolaou or “Pap Smear” technique).

14. Benign Tumours • Appear under the microscope like the tissues they came from • Remain localized and do not spread • Usually do not cause problems unless they grow in a confined space ie. the brain

16. Malignant Tumours • Do not resemble the tissue or cell of origin • Often have irregular structures, large variable nucleus, little cytoplasm, evidence of mitosis, little specialized structures • • Invade surrounding tissues

19. Cancer Metastasis • Cancers invade other tissues and spread to other parts of the body – this is called metastasis • • Metastasis can be local or distant • • Spread of cancer may depend on the type of cancer ie some are more likely to spread than others • eg. small cell lung cancer usually metastatic at time of patient presentation

20. Metastasis occurs in several stages and can occur via several routes • • Local • • Lymphatic • • Blood

22. For cancer cell to metastasize it requires genetic change • • These changes lead to change in the cells function and appearance • • Decreased ability of the cells to adhere to neighbouringcells • • Increased ability of the cancer cells to move

23. Cancer cells extend into surrounding tissue by degrading extracellular matrix • -ie. secrete proteolytic enzymes- cancer cells migrate into lymphaticsand blood vessels • Cancer cells need to be able to provide an adequate blood supply • Angiogenesis – development of a new microcirculation • Cancer cells that acquire these characteristics have a growth advantage, will be clonally selected and given a suitable environment will grow and proliferate

24. The cancer cell acquires growth advantages via mutations to DNA -iecancer is a genetic disease • • Daughter cells inherit the genetic mutations and therefore inherit the growth advantage • • Cancer cells from an individual cancer tend to look the same - all related as the daughter cells inherit the same abnormalities

25. Cancer cells are clonal • Even when a cancer has spread the origin of the cell can usually be traced back to a single cell of origin • • The original cancer cell has a growth advantage – it can grow, divide and invade better than normal cells • The cancer cell has undergone a transformation which gives it a growth advantage

30. Different types of cancer occur as there are many different cell types in specific tissues and organs • • About 85% of all cancers are Carcinomas arising from the skin, and epithelial cells that line the organs - examples include breast cancer, lung cancer, colon cancer • • Sarcomas arise from bone, muscle, blood vessels • • Lymphoma arise from lymphoid cells and leukemias from white cells of the bone marrow

31. What effect does cancer have on a patient ? • Cancer has both local and distant effects

32. LOCAL EFFECTS - 1 • • Cancer displaces normal adjacent tissue • • The function of the tissue deteriorates as the normal cells are replaced by cancer cells which cannot perform the normal cells specialized function • -ie bone marrow – making blood cells. Leukemias replace normal bone marrow • -ie Brain tumours replace normal brain tissue with a specialized function • • Cancer cells are immature and cannot carry out specialized function

33. LOCAL EFFECTS- 2 • Cancers can block vital passages • • The mass of a local or metastasized tumourmay become very large • -i.e. colon cancers may grow locally and block the lumen of the bowel so that it becomes obstructed, even in the absence of distant metastasis • • Tumours may block the normal arterial, venous or lymphatic supply leading to significant symptoms

34. Effects of cancer on the patient • Cancer cells have a very rapid growth and turnover • • The proliferation of cancers leads to a high metabolic rate • • Cancer cells compete with normal cells for nutrition and blood supply • • Other organs may break down their own proteins to nourish the cancer – patient may lose a lot of weight

35. Patient may experience weight loss, fatigue, tiredness. When weight loss is massive and dramatic and the patient becomes profoundly wasted – called cachexia • • Occasionally cancers may secrete hormones which will cause distant effects even when the cancer has not spread – so called non metastatic manifestations of cancer • - ie lung cancer secretes cortisol

36. Cancer spread or metastasis is a common cause of cancer related deaths • • Cancer spread • –distant – via lymphaticslymph nodes, lymphatics and eventually drain into the venous circulation, lungs, heart, and via circulation to other organs • - via blood stream - circulation –distal organs • • Cancer spread may be local • – block a vital organ • - compress vital local tissues, nerves and blood vessels and block lymphatics

37. Mechanical Factors which regulate metastatic deposition • Specific mechanical factors may regulate where a cancer spreads • • The site of the primary tumour • iecolon or breast or kidney and where the venous drainage from that organ drains to. • • For example the liver is the main site of spread from colon cancer

40. The actual size of the cancer cell may regulate the retention of the cell in specific organ systems. • • Both the lung and the liver are frequent, serious sites for the spread of cancer. This may relate to the size of the cancer cells (20 micron) versus the site of the capillaries in these organs – 3-8 micron, so the cancer cells get stuck and then adhere and grow in that site

44. Why do cancers preferentially spread to somesites? • 1/10 women will get breast cancer • Many men will get prostate cancer • Patients with breast and or prostate cancer frequently get bone metastases (may not relate to having an aggressive tumour) • Bone metastases • – lead to hypercalcaemia • - osteolyticlesions (holes in bone ) • - fractures • - osteoporosis

46. Lytic Blastic

47. Types of bone metastases • Bone metastasis is often classified as either • a |osteolyticor • b | osteoblastic, and one of these effects is usually predominant. • For example • metastases from breast and lung tumours are generally osteolytic, whereas metastases from prostate cancer are generally osteoblastic. • However, most blastic metastases have a resorptive component, and most lytic lesions are accompanied by some attempt at repair or bone formation.

48. Cancers may spread specifically to bone because the bone matrix or cytokines secreted by the cancer such as PTHRP enhance cancer growth

49. Cancer Spread to Bone • Effects – • • May cause severe pain • • Weaken bone and causes pathological fractures • • Weaken bone and cause deformities –nerve compression, spinal cord ompressionas a result of vertebral body collapse • • Hypercalcaemia

50. Cancer Dormancy • Some cancers may reappear decades after the excision of the primary tumour and there may have been no evidence of cancer for years – cancer dormancy • • Seen with cancer of the breast and melanoma • Several studies have suggested cancer dormancy may result from failure of the cancer micrometastasisto develop its own blood vessels – therefore the tumour may survive but not expand.