Training Cancer July 2014

1. Training Cancer July 2014

2. Content • What Is Cancer? – An Overview • Origin of Cancer • Cancer Facts • Risk Factors • Prevention • Early Detection and Screening • Staging • 2. Cancer therapy • Systemic Therapy • Hormone Therapy • Targeted Therapy Click on thetitle toredirecttothepageswithfurtherinformation! Click toreturntothispage!

3. 1. What Is Cancer? – A Medical Overview A group of 100 different diseases Cancer is the result of the uncontrolled, abnormal growth of cells These cells form a lump or mass called a tumorSome cancer, however, such as blood cancer, do not form tumors Tumorscan be • benigndo not spread to other parts of the body and are usually not life threatening • malignantgrow and invade other tissues in the body

4. Benign or Malignant Tumor?

5. a) Origin of Cancer – Gene Mutation

6. How do Mutations Occur ? A gene mutation is a permanent change in the DNA sequence that makes up a gene. Mutations range in size from a single DNA building block (DNA base) to a large segment of a chromosome. Gene mutations occur in two ways: they can be inherited from a parent or acquired during a person’s lifetime. This type of mutation is present throughout a person’s life in virtually every cell in the body. Acquired mutations occur spontaneously in the DNA of individual cells at some time during a person’s life. These changes can be caused by environmental factors such as ultraviolet radiation from the sun, or can occur if a mistake is made as DNA copies itself during cell division. Acquired mutations in somatic cells cannot be passed on to the next generation.

7. b) Cancer Facts – Statistical Keywords • Incidence: number of newly diagnosed cases during a specific time period • Mortality: number of deaths during a specific time period • Survival: proportion of patients alive at some point after the diagnosis of their cancer • Prevalence: number of cases alive on a certain date • Lifetime Risk: probability of developing or dying from cancer, in the course of one's lifespan • Statistically significant: describes a mathematical measure of difference between groups. The difference is said to be statistically significant if it is greater than what might be expected to happen by chance alone

8. Cancer Facts - Epidemiology • Cancer is a leading cause of death worldwide • Deaths from cancer in the world are projected to continue rising, with an estimated 9 million people dying from cancer in 2015 and 11.4 million dying in 2030. • The most frequent cancer types world wide are: • Men: lung, stomach, liver, colorectal, oesophagus and prostate • Women: breast, lung, stomach, colorectal and cervical

9. Cancer - Incidences (Age Standardized Rates)

10. Cancer – Incidences by Location • Stomach cancer for men of all ages • - highest in developing countries such as Asia and South America • - lowest in North America, parts of Africa, India • Cervical cancer is • - high in developing regions of the world including Latin America, Africa and India • - low in North America, Europe and Australia • Lung cancer incidence is high in developed countries as well as those countries undergoing economic transition, such as China. • Cancer • - with the highest incidence in developed countries include breast and prostate cancer (North America, Europe and Australia) • - and with much lower incidence in Asia and Africa

11. Cancer Types – Incidence and Mortality US

12. Cancer Types – Incidence and Mortality US • About 1,7 million new cancer cases are expected to be diagnosed in 2013* • 13.7 million Americans with a history of cancer were alive on January 1, 2012 (Prevalence) • In 2013, about 580, 350 Americans are expected to die of cancer, almost 1,600 people per day • The 5-year relative survival rate for all cancers diagnosed between 2002 and 2008 is 68%, up from 49% in 1975-1977 • *not included are carcinoma in situ (non-invasive cancer) of any site except urinary bladder, and does not include basal cell and squamous cell skin cancers

13. c) Risk Factors • Anything that increases a person's chance of developing a disease such as cancer. • Controllable: tobacco use, physical activity, diet, weight, tanning ... • Uncontrollable: age, ethnicity, ... • Risk factors help doctors identify people who may be at higher risk of developing cancer. • People who have close relatives with cancer or close relatives who have died from cancer, especially at a younger age, may be at higher risk. • People who have a history of cancer may benefit from screening tests at an earlier age or on a more frequent basis. People with a known genetic syndrome in the family may consider genetic testing.

14. d) Primary Prevention • Quit smoking • Limit exposure to UV rays, use sun-lotion • Regular physical activity • Diet

15. e) Secondary Prevention – Early Detection and Screening • Early detection increases recovery • Important are regular screening tests • Breast • Colon and rectum • Cervix • Prostate • Testes • Mouth and mouth area • Skin • Self-examination for • breast, skin, and testicular cancers, ...

16. 7 Warning Signs Change in bowel or bladder habits A sore that does not heal Unusual bleeding or discharge Thickening or lump in breast or else-where Indigestion or difficulty in swallowing Obvious change in wart or mole Nagging cough or hoarseness

17. f) Staging • Cancer may be located in one place only (primary tumor, carcinoma in situ) • Sometimes cancer will spread to the lymph nodes tiny, bean-shaped structures that filter the flow of lymph, their clear fluid plays a role in the body's immune system • Cells from malignant tumors can also break away and travel to other parts of the body, where they can continue to grow  metastasis • Metastatic cancer is named for the part of the bodywhere it started, e.g. breast cancer spreads to the lungs,it is called metastatic breast cancer

18. Staging - Definition ... is the process of describing the • size • location of the tumor(s) • spread to other parts of the body ... is essential in determining therapy and assessing a person's prognosis

19. Staging Systems Different staging systems, e.g. TNM: T... size of the primary tumor N... absence or presence of cancer in the regional lymph nodes M... absence or presence of distant metastasis, or cancer that has spread to other areas of the body. Stages are written as Roman numerals I, II, III, or IV Lower stage cancers  better prognosis Stage „0“ cancer means the cancer is confined to the place where it started and has not invaded any surrounding structures. Stage „0“cancer is also called cancer in situ.

20. Staging Example for Breast Cancer

21. 2. Cancer Therapy – Treatment Options • Surgery • Radiotherapy • Systemic Therapy • (Chemo, Hormone, or Targeted Therapy) • Alternative treatmenttreatments, techniques, and products • that are not considered to be conventional or • standard medicine

22. a) Systemic Therapy – Functional Classes of Molecules

23. Chemotherapy – Principle of Action (1) Chemotherapy is effective because the drugs used effect some phase of the cell life cycle. Each cell goes through a four phase cycle in order to replicate itself. • G1, the cell prepares to replicate its chromosomes • S, and in this phase DNA synthesis occurs and the DNA is duplicated • G2, when the RNA and protein duplicate • M, is the stage of actual cell division. In this final stage, the duplicated DNA and RNA split and move to separate ends of the cell, and the cell actually divides into two identical, functional cells.

24. Chemotherapy - Molecules • Alkylating substances • Antimetabolites • Plant alkaloids • Antibiotics • Platinum derivatives • Hormones • Cytokines

25. Chemo – The Molecules and their (Main) Action Alkylating Substances (cross links) Antimetabolites (incorporation) Platins (complex with DNA) Antibiotics (intercalating) Plant Alkaloids (block cell division)

26. b) Hormone Therapy • Hormones are substances that function as chemical messengers in the body. They affect the actions of cells and tissues at various locations in the body, often reaching their targets through the bloodstream. • Hormone therapy (also called hormonal therapy, hormone treatment, or endocrine therapy) slows or stops the growth of hormone-sensitive tumors by blocking the body’s ability to produce hormones or by interfering with hormone action. Tumors that are hormone-insensitive do not respond to hormone therapy.

27. c) Targeted Therapy • Targeted cancer therapies are drugs or other substances that block the growth and spread of cancer by interfering with specific molecules (“targets”) involved in tumor growth and progression. • By focusing on molecular and cellular changes that are specific to cancer, targeted cancer therapies may be more effective than other types of treatment and less harmful to normal cells. • Most targeted therapies are either small-molecule drugs or monoclonal antibodies. • Small-molecule drugs are typically able to diffuse into cells and can act on targets that are found inside the cell. • Most monoclonal antibodies cannot penetrate the cell’s plasma membrane and are directed against targets that are outside cells or on the cell surface.

28. Targeted Therapy – Example Imatinib in CML • most cases of chronic myeloicleukemia(CML) are caused by the formation of a gene called BCR-ABL. • This gene is formed when pieces of chromosome 9 and chromosome 22 break off and trade places. One of the changed chromosomes resulting from this switch contains part of the ABL gene from chromosome 9 fused to part of the BCR gene from chromosome 22 (“target”). • The protein normally produced by the ABL gene (Abl) is a signalling molecule that plays an important role in controlling cell proliferation and usually must interact with other signalling molecules to be active. • However, Abl signalling is always active in the protein (Bcr-Abl) produced by the BCR-ABL fusion gene. This activity promotes the continuous proliferation of CML cells.

29. Targeted Therapy – Example Imatinib in CML con‘d

30. Targeted Therapy – Example Imatinib in CML con‘d

31. Immunomodulators, e.g. Interferones (IFNs) • IFNs belong to the large class of glycoproteins known as cytokines • Interferons are named after their ability to "interfere" with viral replication within host cells • IFNs have other functions • they activate immune cells, such as natural killer cells and macrophages • they increase recognition of infection or tumor cells by up-regulating antigen presentation to T lymphocytes

32. Cancer Treatment - Side Effects Chemotherapy is very effective in killing cancer cells, but it also affects normal cells as well. Typical side effects of chemotherapy include: • gastrointestinal tract problems • hair loss • skin rashes • fatigue and infertility • low blood cell counts Chemotherapy affects the rapidly dividing blood cells in the bone marrow much like it affects cancer cells, and many blood cells die. • Decreased production of healthy red blood cells, which carry oxygen, can lead to anaemia • A decrease in white blood cells, cells that fight diseases, can lead to infections • A reduced number of platelets impairs the clotting ability of the blood, which in turn slows healing from injuries

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34. References • Nature Reviews Cancer 4, 909-917 (November 2004) • 2013 American Cancer Society, Surveillance Report • http://www.yourdiseaserisk.harvard.edu/ • www.cancer.gov

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