1. Understanding Cancer: Current Scientific Research on Causes, Diagnostics, and Treatments. www.ctoam.com

2. In this presentation we’ll cover: How cancer develops and the role of genes and stem cells in its development. The effectiveness and limitations of current standard treatments. www.ctoam.com

3. In this presentation we’ll cover: Diagnostic and imaging options that have been proven to enhance treatment effectiveness. The benefits and misconceptions of clinical trials. www.ctoam.com

4. This presentation consists of two key sections: 1. Cancer 101 - Understanding Current Issues In Cancer & 2. Ensuring That You Are Making Informed Choices www.ctoam.com

5. Cancer 101 It is now widely accepted that all cancers are caused by adult stem cells (or cells with stem-cell like properties). www.ctoam.com

6. What is an adult stem cell? The progenitor (originator) of a group of cells of a specific type Occur in roughly 1 out of 6 million body cells. Used to repair and replace body cells. www.ctoam.com

7. What is an adult stem cell? Exist in regions referred to as stem cell niches, where they remain in a dormant state (quiescence) until activated. Each type of tissue contains it’s own stem cell niche. www.ctoam.com

8. What is an adult stem cell? All stem cells have unique features that allow them to avoid destruction during treatment. However, it is their ability to exist in a dormant state (quiescence) until activated, that is currently inhibiting standard treatments. www.ctoam.com

9. The 2 stages of stem cell activation There are two key stages of stem cell activation: 1. Proliferation. 2. Differentiation. www.ctoam.com

10. The 2 stages of stem cell activation In The Proliferation Stage: The stem cell makes multiple copies of itself. In The Differentiation Stage: The multiple copies are converted into the required cell type and given a Hayflick number. www.ctoam.com

11. The 2 stages of stem cell activation The Hayflick number is the number of times a normal cell will divide before it stops and dies. The important point here is that once a cell has differentiated, it has a finite lifespan. www.ctoam.com

12. Stem cell life cycle Progenitor cell (proliferation) Mature cell (differentiation) Stem cell (dormant) Self renewal (Activation) www.ctoam.com

13. Stem cell life cycle www.ctoam.com There are two imports points here: 1.A stem cell makes an exact copy of itself, which remains dormant in the stem cell niche. 2.A stem cell also produces a large amount of progenitor cells, which then differentiate into the required type of cells.

14. Stem cells and cancer The problem with stem cells is that sometimes, due to mutations, a stem cell is not provided with the cues for differentiation and it gets stuck in a never ending cycle of proliferation, making many copies of itself. This is what we call cancer. www.ctoam.com

15. Genes and cancer 1.A gene is the DNA template that is used to make a protein or enzyme used by the body. 2.Genes are composed of 4 DNA molecules referred to as A, T, G and C. www.ctoam.com

16. Genes and cancer 1.The exact order of these 4 DNA molecules determines the structure of the gene (and its final product). 2. Changing the order that the DNA molecules are arranged in can destroy the function of the gene and is called a mutation. www.ctoam.com

17. Genes and cancer 1.A carcinogen is anything that can change the order of the DNA molecules in a gene. 2. Specific carcinogens can cause mutations that are specific to each type of cancer. www.ctoam.com

18. Genes and cancer There are two key types of genes involved in cancer: 1. Oncogenes. 2. Tumor suppressors. www.ctoam.com

19. Genes and cancer Oncogenes (tumor causing genes): 1.Cause proliferation. 2. Are turned on (expressed) or over-expressed in cancers. 3. Are mutated in such a way that causes them to stay on. www.ctoam.com

20. Genes and cancer Tumor suppressors (cancer preventing genes): 1. Initiate differentiation. 2. Are inhibited or under-expressed in cancers. 3. There are common mutations and deletions of tumor suppressors that occur in specific forms of cancer. www.ctoam.com

21. Normal stem cell life cycle Progenitor cell (proliferation) Mature cell (differentiation) Stem cell (dormant) Self renewal (Activation)(Oncogenes)(Tumor supressor genes) www.ctoam.com

22. Cancer stem cell life cycle (Oncogenes)(Tumor suppressor genes) Self renewal (Activation) Stem cell (dormant) Progenitor cell (proliferation) Mature cell (differentiation) Tumor cells www.ctoam.com

23. Why is this important? There are hundreds of documented oncogenes and tumor suppressor genes in your body. Only four of these genes need to be altered or mutated for cancer to develop. www.ctoam.com

24. Why is this important? Therefore, there are many 1000’s of possible combinations of gene alterations that can lead to cancer in each individual case. The genes mutated are not the same for every person, even if they have the same cancer. www.ctoam.com

25. Why is this important? In order to treat YOUR cancer effectively, it is important to target the genes that have been mutated as they are unique to YOU! This is why success rates for standard chemo/radiation can vary so greatly from one person to another! www.ctoam.com

26. Development of cancer Now let’s explore how cancer develops once the unregulated proliferation of stem cells has begun. www.ctoam.com

27. Metastasis When a cancer cell is stuck in proliferation and hasn’t differentiated, it can live almost anywhere in the body (metastasize) But, how is it that cancer cells travel throughout the body? www.ctoam.com

28. Angiogenesis and metastasis Cancer cells are constantly growing and therefore, need to consume a lot of resources. In other words, they require their own blood supply. Angiogenesis is a process that cancers use to recruit their own blood vessels in order to enable their continued growth. www.ctoam.com

29. Angiogenesis and metastasis The process of angiogenesis is controlled by oncogenes and tumor suppressor genes. Oncogenes are responsible for the initiation of angiogenesis while tumor suppressor genes inhibit it. www.ctoam.com

30. Summary Stem cells remain dormant until activated. Cancer is a disease of the stem cells caused by reduced differentiation and increased proliferation. www.ctoam.com

31. Summary The recruitment of blood vessels (angiogenesis) allows the tumor to grow and to metastasize. Proliferation, differentiation, and angiogenesis are all controlled by genes! www.ctoam.com

32. The standardized approach to cancer treatment utilizes the following three techniques: 1.Surgery: Removes diseased tissues. 2. Radiation: Creates DNA mutations in rapidly dividing cells. 3. Chemotherapy: Chemical interference of rapidly dividing cells. www.ctoam.com Standard treatment methods

33. Limitations of surgery www.ctoam.com Surgery is localized: Limited to treatment of localized disease. Potential to miss stem cells, cells that are in pre-cancerous stages, or cells that have already metastasized.

34. Limitations of radiation Radiation is localized: Non-selective, affects all rapidly dividing cells and is very toxic. Radiation can create new DNA mutations that may lead to more aggressive cancers. www.ctoam.com

35. Limitations of radiation Radiation is localized: Angiogenesis (cancer cell recruitment of blood vessels) occurs directly after treatment. Only affects reproducing cells during course of treatment (not dormant cancer causing stem cells). www.ctoam.com

36. Limitations of chemotherapy Chemotherapy (generalized): Non-selective, affects all rapidly dividing cells and is very toxic. Chemotherapy can create new DNA mutations that may lead to more aggressive cancers. www.ctoam.com

37. Limitations of chemotherapy Chemotherapy (generalized): Angiogenesis occurs directly after treatment. Only affects active cells during course of treatment (not dormant cancer causing stem cells). www.ctoam.com

38. Radiation and chemotherapy The main difference between radiation and chemotherapy is that radiation is used locally and limited to specific regions of the body, while chemotherapy affects all of the cells in the body. www.ctoam.com

39. Additional concerns: Surgery & Radiation In order for surgery and radiation to be effective, the following concerns need to be addressed: Doctors need to target the stem cell niche as well as the malignant tissue (tumor). Doctors need to ensure they have accurate imaging prior to surgery and treatment to differentiate between normal and tumor tissues. www.ctoam.com

40. Making informed choices: DIAGNOSTICS Before your cancer to be effectively treated, two important things MUST be determined! 1.The exact location of all of your tumors. 2. The unique genetic mutations that drive your cancer. www.ctoam.com

41. Making informed choices: DIAGNOSTICS This requires two diagnostic approaches: 1.Accurate imaging of your tumors. 2. Sequencing of your tumor DNA. www.ctoam.com

42. Making informed choices: Imaging PET/CT Combines CT imaging with positron emission tomography. Shows biological activity within organs and detects cancer in the earliest stages. Uses a cancer-specific glucose solution and a radioactive tracer agent that lights up cancerous hot spots. www.ctoam.com

43. Imaging: PET-CT According to the BC Cancer Agency; In 87 % of cases in which a patient has had a PET-CT scan, the results of the test lead to changes in the initial decisions made by oncologists for planned cancer treatment. www.ctoam.com Making informed choices: Imaging

44. Imaging: PET-CT In other words, without a PET-CT scan, current detection methods are only accurate 13% of the time! PET-CT not only ensures proper targeting of the tumor during surgery and radiation treatments, it helps avoid over-treatment or under-treatment. www.ctoam.com Making informed choices: Imaging

45. Imaging: Normal CT scan www.ctoam.com

46. Imaging: PET/CT www.ctoam.com

47. CT Alone PET/CT www.ctoam.com

48. Making informed choices: Imaging NEW! PET-MRI Better imaging of soft tissues compared to CT. Combines the benefits of MRI and PET without the radiation exposure found in PET-CT. www.ctoam.com

49. Making informed choices: Sequencing Of Tumor DNA Recall that genes are encoded in DNA by the order of the DNA molecules (A, T, C, and G). Changes in the specific order of the DNA molecules are called a mutations and affect how the protein or enzyme functions. www.ctoam.com

50. Making informed choices: Sequencing Of Tumor DNA DNA sequencing is the process of determining specific mutations in genes by comparing the genes found in your tumor to those found in normal functioning versions of the same genes. www.ctoam.com

51. Making informed choices: Sequencing Of Tumor DNA Once we have identified the genes that are mutated in your cancer, then we can make a genetic map that provides you with a roadmap to your recovery! This what we call “Targeted Therapy”! www.ctoam.com

52. Making informed choices: Example - Genetic Map Available from www.kegg.jp

53. Why is this important? Having a genetic map of YOUR tumor allows us to identify targeted drugs that will destroy ANY cell in your body with the specific mutation that the drug was designed to target. www.ctoam.com

54. Why is this important? The benefits of this approach is highly effective destruction of tumor cells without the harsh effects of standard chemo- radiation as the drugs will not affect normal cells that do not have the cancer specific mutation. www.ctoam.com

55. Why is this important? Furthermore, having a genetic map allows us to identify “off label drugs”, or drugs that were designed for a different condition or type of cancer, but happen to target the genetic mutations identified in YOUR cancer. www.ctoam.com

56. Why is this important? And finally, having a genetic map of your tumor allows us to identify diet and supplements that have a scientifically proven role in regulating the genes mutated in YOUR cancer. www.ctoam.com

57. Why is this important? You are probably asking yourself; “But what if I can’t afford the drugs that the DNA sequencing has identified”? In just about every case we have looked at, targeted drugs were available via FREE clinical trials. www.ctoam.com

58. Clinical trials: Clinical trials represent leading-edge medical science. However, less than 5% of adults diagnosed with cancer each year are enrolled in clinical trails. While there are a number of various treatment approaches being offered through clinical trials, 8 out of 10 patients are not aware that this is a viable option for them. www.ctoam.com

59. Benefits of clinical trials In order to be offered to the human population, each clinical trial must show that the approach being tested is superior to standard treatment. Patients are also provided with superior imaging and diagnostics not typically offered in public medical facilities. www.ctoam.com

60. Most do not replace standard treatment, they are a form of adjunct therapy, and as such are offered as an additional treatment to standard treatment. In most clinical trials the standard treatment for the type of cancer is typically used in place of the placebo (control group). Benefits of clinical trials www.ctoam.com

61. Clinical trials are typically FREE. But best of all, their success depends on your survival! Benefits of clinical trials www.ctoam.com

62. How we can help you Personalized options plan (POP) Consulting Advocacy Education

63. How we can help you Thank you for viewing this presentation! If you are ready to get started, follow this link to get started with your recovery. GET STARTED WITH CTOAM GET STARTED WITH CTOAM Click here if you would like to learn more about how we have helped previous patients. PATIENT CASE STUDIES PATIENT CASE STUDIES

64. How we can help you When you hire CTOAM, you are hiring your own personal team of experienced cancer researchers to advocate for you and assist you in your treatment and recovery. We will ensure you are maximizing the potential in every aspect of your treatment. www.ctoam.com

65. Thank you Please visit us at: URL: www.CTOAM.com E-mail: Contact@CTOAM.com Phone: (778) 999-5463