An introduction to cancer
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Cancer is characterized by uncontrolled cell growth and the spread of abnormal cells. It is caused by somatic mutations and disruptions to oncogenes and tumor suppressor genes. Many factors like environment, diet, smoking, and alcohol consumption can influence cancer risk. Researchers are studying the cancer genome to better understand carcinogenesis at the molecular level and identify new targeted therapies.
An introduction to cancer
- 1. An introduction to Cancer SALMAN UL ISLAM 2014-11-05 2013298039 Kyungpook National University
- 2. What is Cancer? Cancer is a group of diseases characterized by unregulated cell growth and the invasion and spread of cells from the site of origin, or primary site, to other sites in the body.
- 3. Benign vs Malignant tumors Benign tumors Malignant tumors Slow growing Capsulated Non-invasive Do not metastasize Well differentiated Suffix “oma” e.g. Fibroma Fast growing Non-capsulated Invasive & infiltrate Metastasize Poorly differentiated Suffix “Carcinoma” or “Sarcoma” http://medicinembbs.blogspot.kr/2011/02/neoplasia.html
- 4. Classification of cancer There are more than 100 types of cancer. These are classified on the basis of tissue of origin. Carcinomas: Cancers of epithelial cells. They constitute approximately 85% of all cancers. Sarcomas: Cancers of mesoderm cells (e.g. bone, muscle). Adenocarcinomas: Cancers of glandular tissue (e.g. breast).
- 6. “Hanahan & Weinberg defined” Hallmarks of cancer
- 7. Cancer usually causes somatic mutations Somatic cells: All the body cells except the reproductive (germ) cells. Germ cells: Either the egg or the sperm cell; a reproductive cell. Almost all of the mutations identified in tumor cells are somatic mutations. These mutations are not passed on to the next generation. Only germline mutations will be passed on to off-spring.
- 8. Cancer usually causes somatic mutations
- 9. Normal body processes regulate body net cells number Cell proliferation, differentiation and apoptosis regulate overall net cell number in an individual. Total 9 cells 4 cells divided 4 cells died 1 cell differentiated Total remaining cells= 9 Apoptosis is blocked in 1 cell 5 cells divided 3 cells died 1 cell differentiated Total remaining cells= 11
- 10. Oncogenes and tumor suppressor genes regulate cancer Oncogene: It is the gene mutated such that its protein product is produced in higher quantities, or has increased activity and therefore initiate tumor formation. It sometimes produces a growth factor receptor that is always in the “ON” state.
- 11. Oncogenes and tumor suppressor genes regulate cancer Tumor suppressor gene: This gene codes for proteins that play a role in inhibiting both growth and tumor formation.
- 12. Oncogenes and tumor suppressor genes regulate cancer Knudson’s two-hit hypothesis
- 13. Influential factors in human carcinogenesis Factors that play an important role in carcinogenesis include: Environment Reproductive life Diet Alcohol Smoking
- 14. Influential factors in human carcinogenesis Environment: Environmental agents were first correlated with specific cancers in 1775 by a British surgeon. Incidence of nasal and scrotal cancer is high in chimney sweeps. Unprotected exposure to sun leads to skin cancer.
- 15. Influential factors in human carcinogenesis Reproductive life: Cancer has a great relation with reproductive life. Women having children have a reduced risk of breast cancer. The risk is higher in Nuns. Nuns have a low incidence of cervical cancer, which is caused by sexually transmitted human papillomaviruses. Kaposi’s sarcoma, which requires immunosuppressive conditions (AIDS) is predominant in Kenyan males.
- 16. Influential factors in human carcinogenesis Diet: It is one of the most influential factors of cancer. Stomach cancer is a predominant cancer in the Japanese population and a minor cancer in the population of the USA.
- 17. Influential factors in human carcinogenesis Alcohol: Chronic alcohol drinking increases the risk of cancer of the mouth, esophagus, and breast, and probable evidence for increased risk of liver cancer. Daily alcohol intake should not exceed 28g (approx. ¼ of a bottle of wine). Genetics and alcoholism. Nature Reviews
- 18. Influential factors in human carcinogenesis Smoking: Smoking causes lungs cancer; the main cancer worldwide. It is also implicated in pancreatic, bladder, kidney, mouth, stomach, and liver cancer.
- 19. Age-adjusted cancer death rates, USA, 1930-2010
- 20. Principles of Cancer therapies Surgery was the earliest strategy used against cancer. It is not precise as cancer cells spread from the primary site. Chemotherapy is preferred, either for cytostatic or cytotoxic effect. The ultimate goal of chemotherapy is to damage the DNA for inducing apoptosis in cancer cells. Chemotherapeutic agents having higher value of therapeutic index are considered safe.
- 21. Therapeutic index Therapeutic index refers to the relationship between toxic and therapeutic dose. Where: TD50 is the dose of drug that causes a toxic response in 50% of the population and ED50 is the dose of drug that is therapeutically effective in 50% of the population.
- 22. Clinical Trials for new anti-cancer drugs Clinical trials are required for testing the new drugs in humans. CERN Foundation, Collaborative Ependymoma Research Network, ohio
- 23. Single-blind and double-blind study Single blind study: Patients don’t know whether they are taking treatment or placebo (control dosage forms). Double blind studies: Both, patient and doctor, are in dark.
- 24. Important molecular targets for anti-cancer drugs There are several families of “star players” in the story of carcinogenesis to be targeted. These interconnect many pathways and can exert several effects in response to a specific signal.
- 25. Protein kinases and Ras protein
- 26. p53 and Retinoblastoma gene (Rb)
- 27. Cancer genome The sequencing and mapping of human genome has paved the way of cancer genomics. Learning the difference between genome of cancer and a normal cell will have a great contribution in designing more powerful and specific drugs. International Cancer Genome Consortium (ICGC) is trying to characterize at least 50 classes of cancer, creating an open access to the entire research community. The international SNP Map Working Group is anlazing single nucleotide polymorphism (SNPs). It will help in identifying mutations within the genome that may be linked with cancer.
- 28. Summary Cancer is the uncontrolled and unregulated growth of cells which metastasize throughout the body. Cancer is a genome disease at the cellular level. Changes in lifestyle can affect cancer risk. Protein kinases are important molecules in carcinogenesis. Cancer genomics is being used to define molecular targets for tumor-specific effects.