Lecture 6 Cancer s most deadly weapon Primary and secondary cancer Main reason cancer can be difficult to cure because it can spread to another part of the body Primary cancer the place in the body where cancer started growing Secondary cancer the place in the body where cancer spreads to and starts growing Cancer spread and mortality 90 of cancer deaths occur because where the cancer ends up not where it begins metastatic cancers allow cancerous cells to colonize a secondary organ by the time a tumor is found cancer cells may have been present for some years but the immune system controlled the spread when cancer cells travel to a vital organ they overwhelm the cells and cause it to shut down Hematologic cancers Hematologic blood cancers kill because the components of the blood are no longer fulfilling their duties Immune system no longer work effectively The platelet count drops which causes hemorrhage Red cells are significantly reduced causing reduced oxygen and the patient has a heart attack Increased white blood cells lead to really viscous blood clogging the arteries Solid tumors Solid tumors kill in mechanical ways Ovarian cancer kills you by obstructing your bowel as does colon cancer Lung cancers usually kill by eroding into an artery or obstructing the airway Breast cancers typically kill by metastases in the brain causing increased intracranial pressure More than 40 of cancer patients die from malnutrition not the cancer itself Tumors induce a hyper metabolic state and secrete a substance called cachectin TNF a that results in weakness and weight loss Most common sites of cancer metastasis Brain headaches seizures vertigo Lymph nodes lymphadenopathy Respiratory cough hemoptysis dyspnea Liver hepatomegaly jaundice Skeletal pain fractures Vasculogenesis and Angiogenesis Vasculogenesis formation of new blood vessels when there are no pre existing ones Angiogenesis formation of new blood vessels from pre existing ones Dr Judah Folkman Experimented with tumors and found that all grew to the same size and stopped Hypothesized that the tumors couldn t grow beyond a certain size without a blood supply Tumors must have some mechanism to induce formation of blood vessels Tumor Angiogenesis Tumors can t grow without the help of blood vessels so they recruit blood vessels to feed them States of Angiogenesis tumors need a fuel supply system for growth more fuel more 2 Early stage angiogenesis 1 Pre angiogenesis aggressive growth development malignant tumor to the point where it can become life threatning 3 Advanced angiogenesis dense network of blood vessels fuels the growth of the capillary and other blood vessel growth promotes rapid tumor Metastasis when cancer cells break off from the tumor and moves to another place in the body The ability to invade differs among cancer cells and tumors Blood flow patterns often dictate where cancers will spread to Few cancer cells survive the voyage through the blood stream Cancer cells are able to invade because decreased adhesiveness activated motility protease production 3 main ways a cancer spreads Local spread Through the blood circulation Through the lymphatic system Steps involved in the Metastatic process Dynamics of the metastatic process 1 Cells grow as benign tumor in epithelium 2 Cells break through basal lamina 3 Then they invade the capillary 4 They adhere to blood vessel wall in liver 5 Escape from blood vessel extravasation 6 Then moves to form metastasis in liver Inhibition of angiogenesis A way to treat cancer Endostatin prevents the blood vessels from responding to angiogenic factors Cancer growth stops when deprived of blood supply
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