College of the Canyons Fall 2009 Scholarly Presentation by Kelly J. Cude, Ph.D.

Transcription

1 - College of the Canyons Fall 2009 Scholarly Presentation by Kelly J. Cude, Ph.D.

2 The War on Cancer On December 23, 1971, President Nixon signed the National Cancer Act into law, declaring, "I hope in the years ahead we will look back on this action today as the most significant action taken during my Administration." From $200+ billion spent 1.5 million papers published Over 15 million lives lost

3 What is Cancer? A family of closely related diseases in which abnormal cells proliferate in an uncontrolled fashion and spread throughout the body. It can take decades for a tumor to develop. T Start 5 years 10 years 20+ years

4 How Cancer Kills 1. Unregulated Division Produces excessive numbers of abnormal cells Normal Cancer 2. Disrupted Architecture Cancer cells destroy the normal structure of a tissue 3. Organ Failure Cancer cells destroy the normal function of an organ causing organ failure

5 How Common is Cancer? 2009 Total new cases* = 1, 479,350 (3,000/day) 2009 Estimated deaths* = 565,680 (1,500/day) Men new cases = 766,130 Women new cases = 713,220 Men Top 3 25% Prostate 15% Lung & bronchus 10% Colon & rectum Women Top 3 27% Breast 14% Lung & bronchus 10% Colon & rectum Lifetime Risk 1:2 Lifetime Risk 1:3 *Excludes basal and squamous cell skin cancers and in situ carcinomas except urinary bladder. Source: American Cancer Society, 2009.

6 How Lethal is Cancer? The probability of surviving cancer depends on (1) the type of cancer and (2) how advanced the disease is at diagnosis. Source: Principles of Cancer Biology (2006) by Lewis J Kleinsmith

7 How is Cancer Treated? (Therapy Mainstays) 1. Surgery cut it out 2. Radiation burn it out 3. Chemotherapy kill it with chemicals Surgery Chemo Radiation

8 Limitations of Surgery While often the first line of defense in cancer maintenance, surgery has several limitations which prevent it from treating or curing many patients. 1. Inoperable Tumors 2. Damage to Normal tissue 3. Potential for Seeding 4. Cannot get all Metastases 5. Tumors near Blood Vessels Metastases Tumor near Aorta

9 Limitations of Radiation (Use of targeted electromagnetic waves) How Radiation Works Use of high energy wave particles (X rays or radioactive elements) to damage DNA and kill cells. External beam Internal seeds Radiation kills both cancer cells AND normal cells = side effects jpg -

10 Limitations of Chemotherapy (Systemic treatment using toxic chemicals) How Chemo Works Toxic chemicals are pumped through the bloodstream to kill dividing cells. Original source: chemical weapons New sources: plants, sea sponges Chemo kills both cancer cells AND normal cells = side effects

11 Millions of People Trends in Death Rates While death from heart disease in the last 30 years has plummeted for persons 65 and over, deaths from cancer have risen slightly. 100* The Aging U.S. Population 65 yrs + 85 yrs SEER data 2006 NCI, NIH.gov Age is the #1 Risk Factor for Cancer Projected by US Census

12 Better Understanding Through Research In order to design BETTER, more effective treatments, scientists must have a BETTER understanding of the disease.

13 Cancer Cells are Hard to Kill 1. Resistant to Cell Death Cancer cells are resistant to cell death (apoptosis) signals making them hard to kill Normal Cells Cancer Cells Chemo Kills Normal Cells Cancer cells become resistant to chemo so that using higher doses kills more normal cells than cancer cells

14 Cancer Cells Recruit Blood Vessels 2. Activate Angiogenesis Recruit blood vessels which bring nutrients to the tumor Without a blood supply tumors would not grow larger than a grain of rice The largest tumor on record weighed 303 lbs. Guinness Book of Records, 2006

15 Cancer Cells Spread Throughout the Body 3. Ability to Metastasize Cancer cells can detach from the original tumor and create many small tumors throughout the body (metastases) 90% of cancer patients die from metastases LUNGS LIVER COLON

16 Cancer Cells are Genetically Unstable 4. Extensive DNA Damage Cancer cells accumulate DNA mutations and chromosomal abnormalities which can disrupt hundreds or thousands of genes! Normal Cell Cancer Cell

17 My Small Contribution to Cancer Research Genetic Pathways that Activate Cell Division in Cancer Cude, K et al. (2007) Journal of Cell Biology 177(2): Angiogenesis Inhibitors in Breast and Prostate Cancer Bauer KS, Cude KJ et al (2000) J Pharmacology Exp Ther 292(1):31-7. Genetic Mutations Contributing to Prostate Cancer Cude KJ et al. (1999) J Molecular Medicine 77(5): Review. Cude KJ et al. (2002) Urology International 68(1): Bennett CL, Price DK, Kim S, Liu D, Jovanovic BD, Nathan D, Johnson ME, Montgomery JS, Cude K, Figg WD. (2002) J Clin Oncol. 20(17):

18 from Targeted therapies have fewer side effects because they target cancer cells, while leaving healthy cells unharmed.

19 ngiogenesis Inhibitors mmunotherapies anotechnology enetic Screening tem Cell Therapies

20 Targeting Tumor Blood Vessels Anti-angiogenesis treatments target and kill tumor blood vessels. Without blood vessels tumors are starved of nutrients needed to grow large and spread. Scientific American Cancer Special Edition 2008

21 Blocking Recruitment of Blood Vessels Under low oxygen conditions, tumors secrete a molecule called VEGF which stimulates nearby blood vessels to migrate towards the tumor. VEGF Secretion Angiogenesis inhibitors interfere with VEGF thus preventing the tumor from receiving oxygen and other nutrients. Center of tumor has died biooncology.com

22 Depriving Tumors of Oxygen Angiogenesis inhibitors can target inoperable tumors (like brain) and have fewer side effects than chemotherapy R. Jain (2008) AZD2171(AstraZeneca) Avastin (bevacizamab) used for colon cancer, non small cell lung cancer, and some forms of breast cancer

23 Harnessing the Immune System Immune cells circulate the body looking for foreigners like viruses and bacteria. Immune cells use cell surface markers to identify self versus non-self cells. Surveillance Detection Attack lymphoma.org

24 Helping Immune Cells Recognize Cancer The last decade of cancer research has focused on identifying markers on cancer cells which can be used to trigger an immune response. These cancer identifiers are known as Biomarkers. Identified Biomarkers Immune cells attacking cancer immune cell cancer cell red blood cell pharmamotion.com.ar

25 Targeted Immunotherapy Researchers have created antibodies that can specifically target cancer BIOMARKERS when injected into a person s bloodstream. Create Antibody Inject Antibody Kill Cancer Antibody Cancer Cell accessexcellence.org, nci.nih.gov

26 Targeted Immunotherapy Using antibodies to specifically target cancer cells REDUCES side effects because they are less likely to harm normal tissues. Therapeutic Antibodies in Use Therapy Biomarker Cancer Rituxan CD20 Non-Hodgkin s Herceptin Her2/Neu Breast Erbitux EGFR Colon, Head/Neck Tarceva EGFR Lung, Pancreatic Avastin VEGF Breast, Colon, Lung Campath CD52 CLL Leukemia Gleevec BCR-ABL CML Leukemia Nexavar VEGF R Liver, Kidney

27 Targeted Radiation (Radioimmunotherapy) Attach radioactive isotopes to antibodies which bind specifically to cancer cells. When injected, these molecules search out and bind to metastases that are too small to surgically remove. Labeled Antibody Bexxar (tositumomab-i131) used to target radiation to B cells in Non-Hodgkin s Lymphoma Cancer Cell

28 Cancer Vaccines Therapeutic (Cure) vs. Preventative (Prevent) Preventative Vaccines Protect recipient from developing that type of cancer. Gardisil for Cervical Cancer, 2006 Hepatitis B for Liver Cancer, 1981 Therapeutic Vaccines Attack an existing tumor and/or prevent recurrence. In Clinical Trials as of 2009

29 Stem Cell Therapy & Targeting Cancer stem cells naturally migrate to their tumor of origin when injected into the blood stream and can easily cross the blood brain barrier. Cancer stem cells have a natural homing signal

30 Targeted Nanotechnology The burgeoning nanotechnology field has created a way to place toxic chemo drugs in a protective shell which is coated in antibodies to target the chemicals to the tumor. Nano SMART BOMB Nanoworms Nanoworms Strings of Iron Oxide antibody coated SMART BOMB web.mit.edu/newsoffice/2008/nanoparticles.jpg

31 Targeted Photothermal Plasmonics Gold coated nanospheres with resonant absorption in the near-infrared (NIR) will heat up when targeted by an infrared laser and photothermally destroy cancerous tumors. Nanospheres cben.rice.edu,

32 Radio Frequency Ablation Therapy In Radiofrequency Ablation Therapy RF energy destroys the tumor by generating heat as the tumor s molecules vibrate. Lung Tumor Before RFA Lung Tumor After RFA

33 Targeted Radiation (Proton Therapy) Protons are accelerated in a cyclotron and focused into a high energy beam which is directed at the tumor. Unlike X rays, protons do not transmit energy beyond the tumor

34 Locations Offering Proton Therapy Loma Linda, CA

35 Genetically Tailored Treatments Each cancer patient has a UNIQUE set of mutations. By identifying EACH PATIENT S set of genetic markers, doctors can provide designer treatments that are tailored for each patient. From L. J. Kleinsmith, Principles of Cancer Biology. Copyright (c) 2006 Pearson Benjamin Cummings.

36 Genetic Assays and Profiling Microarray assays compare the genes in cells from normal tissue to biopsied cancer tissue to identify genetic changes in the tumor. Onc DX Gene Microarray ON in cancer OFF in cancer Mammaprint antonistift-bamberg.de

37 Early Detection Increases Chances of Survival Most tumors are diagnosed at an advanced stage which is associated with a poor prognosis. New research is under way to develop new methods for early detection. 5 Year Survival Rate Stage at Diagnosis Stage I-IIA Stage IIB-III Stage IV

38 Early Detection for Secreted Biomarkers Tumors can release BIOMARKERS into the bloodstream, which can be detected by a simple blood test before cancer symptoms develop. PSA: Prostate CA-125 : Ovarian CA27.29: Breast CEA: Breast, Colon E6: Cervical NDRG4: Colon Secreted Biomarkers

39 Early Detection: A Cancer Breathalyzer When subjects blew onto a gold plated nanosensor, it detected trace chemicals (VOC) emitted from lung cancer cells 86% of the time, even before patients showed symptoms of disease. Scientists at University of Haifa, Aug

40 What Does the Future Hold? HOPE!