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Cancer : when our own cells become the enemy

Cancer : when our own cells become the enemy. Erin Martinez, Ph.D. Trevecca University Physician Assistant Program September 30, 2013. What is cancer?. = a malignant tumor. = cells that escape their normal surroundings, invading locally and travelling to distant locations .

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Cancer : when our own cells become the enemy

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  1. Cancer: when our own cells become the enemy Erin Martinez, Ph.D. Trevecca University Physician Assistant Program September 30, 2013

  2. What is cancer? = a malignanttumor = cells that escape their normal surroundings, invading locally and travelling to distant locations = abnormal cell mass that develops when cells grow too much benign

  3. Moving from normal tissue to cancer Normal cells Benign tumor Basement membrane Blood vessel Malignant tumor = CANCER Bastid J, Ciancia C, Puisieux A, Ansieau S . Role of TWIST proteins in cancer progression. Atlas Genet CytogenetOncolHaematol. December 2009 .

  4. What does cancer look like? Breast cancer: normal to cancer Ductal carcinoma in situ DeNardo and CoussensBreast Cancer Research 2007 9:212

  5. What does cancer look like?Colon cancer: normal to cancer Cancer Normal Tumor Rose and Wu. The Internet Journal of Pathology. 12:1. 2011

  6. What does a cancer cell look like?The Hallmarks of Cancer CellHanahan and Weinberg, 2000.

  7. Hallmarks of Cancer: physiological changes 1 Keeping the foot on the gas of growth 3 2 Cells don’t die easily No brakes on growth! 6 5 Cells get more blood supply Cells escape and spread 4 Cells divide forever, and ever…

  8. Cell growth in cancer • Hallmarks 1 and 2: Keeping the foot on the gas of growth and no brakes on growth! • Progress though the cell cycle more quickly than a normal cell • Don’t follow normal rules for stopping the cell cycle (checkpoints) http://eishinoguchi.com/checkpoint.htm

  9. Cancer cells resist death • Hallmark 3: Cells don’t die easily • Things that can usually cause programmed cell death (apoptosis) • DNA and protein damage • lack of nutrition/oxygen • buildup of waste • lack of survival signals from other cells • death signals from other cells • Cancer cells ignore these and survive!

  10. Cancer cells are immortal • Hallmark 4: cells divide forever, and ever… • Normal cells stop growing or die when telomeres are gone • Cancer cells activate telomerase or do abnormal kinds of DNA recombination to survive! http://www.med.nyu.edu/skirball-lab/sfeirlab/Research.html

  11. Cancer cells induce angiogenesis • Hallmark 5: cells get more blood supply • Fast growing cells beginning to form a tumor need more nutrients and need to get rid of more waste than local blood vessels can provide • Promote formation of new blood vessels (angiogenesis) with signaling molecules (example: VEGF) http://www.cancer.gov/cancertopics/understandingcancer/angiogenesis/AllPages

  12. Cancer cells are on the move Prostate cancer metastasis imaged with PET • Hallmark 6: cells escape and spread • Normal cells die when they loose contact with surrounding cells or the basement membrane • Cancer cells gain ability to migrate locally and sometimes flow through bloodstream and grow in a distant site (metastasis) J Nucl Med February 2006 vol. 47 no. 2 287-297

  13. How do normal cells become cancerous? • Changes in gene expression and activity • most often caused by mutations • Mutations = changes in DNA that alter expression or activity of the gene • Two main types of genes with mutations in cancer: • Oncogene – genes that normally promote growth are mutated to be hyperactive • Tumor suppressor – genes that normally inhibit growth are mutated to be inactive • It takes several genetic alterations to cause cancer

  14. How do we fight cancer? • First surgery, then other therapies • Target fast-growing cells • - Radiation • - Chemotherapy Kill all fast-growing cells - bad side effects

  15. Other new cancer therapies Anti-angiogenesis therapy Avastin – anti-VEGF antibody for metastatic colorectal cancer, and advanced non-small cell lung cancer Targeted therapy to a oncogene in a tumor cell Gleevec - inhibitor of oncogene in chronic myelogenous leukemia Erbitux – inhibitor of oncogene in colorectal and head/neck cancer Herceptin - inhibitor of oncogene in breast cancer Activating immune system against cancer cells Provenge– activate man’s own immune cells against prostate cells

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