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Bohomolets Oncology Lecture year 5


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By Dr.Olga Lobanova from Oncology department

Published in: Health & Medicine
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Bohomolets Oncology Lecture year 5

  1. 1. Cancer <ul><li>is the term used to describe uncontrolled cell growth which can lead to tumour formation </li></ul><ul><li>may be either </li></ul><ul><ul><li>benign (noninvasive growth, no metastases) </li></ul></ul><ul><ul><li>malignant (invasive growth, metastases). </li></ul></ul>
  2. 2. Cancer will have a direct effect on 1 in 3 people during their lifetime. Our increased life expectancy and modern lifestyles (diet, smoking, alcohol and stress) all act as contributory factors. The most common cancers amongst men are prostate, colorectal and lung with the incidence of these cancers expected to increase by 57% by 2020(Irish Cancer society). The most common cancers amongst women are breast, lung and bowel cancers and over the last 20 years the incidence of breast cancer has increased by 50% (CRUK). 350 000 new cases of colorectal cancer are reported in the western world per year while in Europe there are approximately 430 000 new cases of breast cancer diagnosed every year.
  3. 3. <ul><li>Cancer rates could further increase by 50% to 15 million new cases in the year 2020, according to the World Cancer Report, the most comprehensive global examination of the disease to date. However, the report also provides clear evidence that healthy lifestyles and public health action by governments and health practitioners could stem this trend, and prevent as many as one third of cancers worldwide. </li></ul><ul><li>In the year 2000, malignant tumours were responsible for 12 per cent of the nearly 56 million deaths worldwide from all causes. In many countries, more than a quarter of deaths are attributable to cancer. In 2000, 5.3 million men and 4.7 million women developed a malignant tumour and altogether 6.2 million died from the disease. The report also reveals that cancer has emerged as a major public health problem in developing countries, matching its effect in industrialized nations. </li></ul>
  4. 5. Types <ul><li>Carcinomas are malignancies that arise from epithelium. </li></ul><ul><li>Adenocarcinomas are malignancies that arise from epithelium and have a glandular component. </li></ul><ul><li>Sarcomas are malignancies that arise from mesodermal tissues. </li></ul>
  5. 6. Neoplastic transformation. <ul><li>Neoplastic cells have &quot;escaped&quot; from the normal homeostatic inhibition (or regulation) of cell proliferation. </li></ul><ul><li>Causes of neoplastic transformation are listed below with illustrative examples of human tumors. Because no single etiology is known for most human cancer, it is assumed that multiple factors lead to neoplastic trans formation. </li></ul>
  6. 7. Carcinogens <ul><li>Chemical </li></ul><ul><li>Physical </li></ul><ul><li>Hereditary factors </li></ul><ul><li>Geographic factors </li></ul><ul><li>Oncogenic viruses </li></ul>
  7. 9. Examples of human oncogenes
  8. 10. Primary prevention is the priority in cancer fighting. <ul><li>Smoking control </li></ul><ul><li>Dietary factor </li></ul><ul><ul><li>an increase in consumption of fresh fruit and vegetables, low-calory products, intensification of physical activity and lowering of body mass produce a reduction in the incidence of cancer of the stomach, large bowel, breast, corpus uteri, prostate. </li></ul></ul><ul><li>Prevention of infection including vaccination is the most efficient method for prevention of cancer of the liver, cervix uteri, some leukemias and lymphomas, H. pylori associated stomach cancer. </li></ul><ul><li>Control of environmental hazards such as intensive ultraviolet radiation, ionizing radiation, air and soil pollution decrease the rate of skin cancer, melanoma, etc. </li></ul>
  9. 11. <ul><li>The main adaptive mechanisms involved in the carcinogenic process. As a result of the action of carcinogenic agents, and in relation to the functional status of the affected cells, a number of systems are triggered off: detoxification and conjugation systems, the metabolisation of the said agents, DNA repairing enzymes, increased shock proteins (HSP), the induction of clonal proliferation. All these systems are valuable to the survival of the body and the species and culminate in the apoptosis of damaged cells as the last attempt at adaptation of a social kind for the good of the body. When these compensation mechanisms prove ineffective, imprecise or are exceeded by cell adaptive capacity, the resulting structural and functional alterations trigger off (induction) a very long process which often lasts between one and two thirds of the body's life, in various stages, multistep and multifactorial: this neoplastic transformation leads to a purposeless, egoistic, anarchic proliferation of cells which wish to survive at all costs, even to the detriment of the body of which they form part. Following the exhaustion of cell adaptive defences, there is an accumulation of additional genetic alterations (promotion and progression), the cells become manifestly neoplastic and continue their egoistic adaptation, according to the laws of natural selection: the cells which survive are those which adapt best to the hostile environment of the host's body, which are unaffected by proliferation control mechanisms (contact inhibition, differentiation factors, apoptosis, etc.), which make the best of the growth factors present in their microenvironment, which accomplish the so-called decathlon of the metastatization process, namely acquiring new capacities which can overcome the basal membrane, invade tissues to which they are attracted and continue to proliferate. Manifestly neoplastic cells become not self at a later stage, managing to escape the immune system using various adaptive mechanisms which induce immune tolerance/anergy. From this point of view, cancer may be regarded as an incidental factor in the host's cell adaptation processes; the latter are much more important from a biological point of view and their absence is incompatible with life: cancer might therefore be regarded as a cell adaptation pathology. </li></ul>
  10. 12. Stages of cancerogenesis <ul><li>structural and functional alterations trigger off - induction </li></ul><ul><li>accumulation of additional genetic alterations - promotion </li></ul><ul><li>unaffected by proliferation control mechanisms (contact inhibition, differentiation factors, apoptosis) - progression </li></ul>
  11. 13. Genetic systems implicated in carcinogenesis <ul><li>There are two main categories of genes involved in cancer: protoconcogenes and tumor suppressor genes. The development of cancer can require the production of several successive gene accidents within a given cell. Most of these alterations appear to be somatic changes. Only one of these two steps would involve germinal processes and only in hereditary tumors. When altered, these genes, implicated in cell proliferation, differentiation and normal cell death, contribute to the initiation and/or the progression of tumors. Other genes have an indirect effect on the malignant transformation and thus complete the action of oncogenes and suppressor genes at certain stages of cancerogenesis. The genes implicated in individual susceptibility to cancer is an example (genes coding for DNA repair enzymes and for proteins which inactivate exogenous cancerogenenic agents. Others are genes coding for growth factors and angiogenic factors, genes involved in metastatic dissemination including those which code for proteases and adherence proteins, and finally genes affecting chemoresistance. </li></ul>
  12. 15. Metastatic progression
  13. 16. Acquisition of tumorigenic phenotype and clonality
  14. 17. The Vogelstein model of multistep carcinogenesis
  15. 18. Intervention period for carcinogenesis
  16. 19. Pathogenesis of metastasis
  17. 20. Frequency of metastatic sites
  18. 21. Interation between tumour cells, endothelial cells and macrophages
  19. 22. Tumour Grading <ul><li>well differentiated </li></ul><ul><li>middle differentiated </li></ul><ul><li>poorly differentiated </li></ul><ul><li>undifferentiated </li></ul><ul><li>Depends on: </li></ul><ul><ul><li>degree of cellular anaplasia </li></ul></ul><ul><ul><li>mitotic activity </li></ul></ul>
  20. 23. Tumor staging (AJCC, IUAC) <ul><li>T describes the primary tumor – the size of the tumour at its primary site and/or the involvement of local structures describe the tumour topography. </li></ul><ul><li>TO: no evidence of primary tumor </li></ul><ul><li>TIS (in situ): tumor limited to mucosa </li></ul><ul><li>T1: tumor limited to mucosa or submucosa </li></ul><ul><li>T 2: tumor to but not through the serosa </li></ul><ul><li>T3: tumor through the serosa but not into adjacent organs </li></ul><ul><li>T4: tumor into adjacent organs (direct extension) </li></ul><ul><li>N describes the involvement of regional lymph nodes with metastatic spread. </li></ul><ul><li>NO: no metastases to lymph nodes </li></ul><ul><li>N1: only perigastric lymph nodes within 3 cm of the primary tumor </li></ul><ul><li>N2: only regional lymph nodes more than 3 cm from tumor but removeable at operation </li></ul><ul><li>N3: other intra-abdominal lymph nodes involved </li></ul><ul><li>M describes documented evidence of distant metastases. </li></ul><ul><li>M0: no distant metastases </li></ul><ul><li>Ml: distant metastases </li></ul>
  21. 24. Stage grouping. <ul><li>Staging is necessary to choose the appropriate therapy and to assess the prognosis. It also allows investigators to report their results in a standardized way so that conclusions regarding treatments and their outcomes are interpretable. </li></ul><ul><li>Stage 0: TIS, NO, M0 </li></ul><ul><li>Stage 1: T1, NO, M0 </li></ul><ul><li>Stage 2: T2 or T3, NO, M0 </li></ul><ul><li>Stage 3: T1-3, N1 or N2, M0 </li></ul><ul><li>Stage 4: any T4, any T3, any N3, any Ml </li></ul>
  22. 26. Clinical manifestations of cancer <ul><li>Seven classic symptoms of cancer are: </li></ul><ul><li>Change in bowel or bladder habits </li></ul><ul><li>A sore that does not heal </li></ul><ul><li>Unusual bleeding or discharge </li></ul><ul><li>Thickening or lump in the breast or elsewhere </li></ul><ul><li>Indigestion or difficulty swallowing </li></ul><ul><li>Obvious change in a wart or mole </li></ul><ul><li>Nagging cough or hoarseness </li></ul>
  23. 27. Other manifestations <ul><li>Growth, causing a mass, obstruction, or neurologic deficit </li></ul><ul><li>Growth into neighboring tissues, causing pain, paralysis, fixation, or immobility of a palpable mass </li></ul><ul><li>Tumor necrosis, causing bleeding or fever </li></ul><ul><li>Systemic manifestation, such as thrombophlebitis, endocrine symptoms due to hormones secreted by the tumor, and cachexia </li></ul><ul><li>Metastatic spread as the first symptom, such as enlarged lymph nodes, neurologic symptoms, or pathologic bone fractures </li></ul>
  24. 28. Screening tests for cancer detection. <ul><li>Mammography (annually after age 40-50) </li></ul><ul><li>Stool for occult blood and digital rectal examination (annually after age 50) </li></ul><ul><li>Pap smear of the cervix (every 3 years after two negative tests 1 year apart) </li></ul>
  25. 29. Diagnostic procedures <ul><li>Types of biopsy </li></ul><ul><li>Aspiration biopsy </li></ul><ul><li>Needle biopsy </li></ul><ul><li>Incisional biopsy </li></ul><ul><li>Excisional biopsy </li></ul><ul><li>Staging laparotomy </li></ul>
  26. 30. Imaging studies <ul><li>X-ray images </li></ul><ul><li>computed tomography (CT scan) </li></ul><ul><li>ultrasound </li></ul><ul><li>endoscopic examinations </li></ul><ul><li>magnetic resonance imaging (MRI) </li></ul><ul><li>positron emission tomography (PET) </li></ul><ul><li>radioisotope scanning </li></ul><ul><ul><li>bone scanning </li></ul></ul><ul><ul><li>lymphoscintigraphy </li></ul></ul>
  27. 31. Multimodality cancer therapy. <ul><li>Basic methods </li></ul><ul><ul><li>Surgery </li></ul></ul><ul><ul><li>Radiation </li></ul></ul><ul><ul><li>Chemotherapy </li></ul></ul><ul><ul><li>Immunotherapy </li></ul></ul><ul><li>Surgery and radiation therapy </li></ul><ul><li>Chemotherapy and immunotherapy </li></ul><ul><li>Neoadjuvant therapy </li></ul><ul><li>Adjuvant therapy </li></ul>
  28. 32. Cancer surgery. <ul><li>Curative resection. </li></ul><ul><ul><li>Wide local resection. </li></ul></ul><ul><ul><li>Radical local resection. </li></ul></ul><ul><ul><li>Radical resection with en bloc excision of lymphatic drainage </li></ul></ul><ul><ul><li>Super radical resections </li></ul></ul><ul><li>Other surgical resections </li></ul><ul><ul><li>Resection of recurrent cancer </li></ul></ul><ul><ul><li>Resection of metastases </li></ul></ul><ul><ul><li>Palliative surgery </li></ul></ul><ul><ul><li>Debulking </li></ul></ul>
  29. 33. Cytotoxic chemotherapies <ul><li>have formed the cornerstone of frontline cancer therapy for the last 30 years. </li></ul><ul><li>While effective in some patients this group of drugs has been hampered by their toxic side effects, high relapse rates and an increasing incidence of drug specific resistance. In recent years the introduction of antibody targeted therapies has led to major improvements in cancer care. The development of antibodies to different targets can overcome the resistance observed with conventional chemotherapies by targeting different pathways. The success of several antibody based therapies in the clinic, such as Avastin and Herceptin has increased demand for monoclonal antibody therapies with the market expected to reach $26 billion by 2010. Antibody based therapies are now recognized as key components of modern frontline cancer therapies. Fusion Antibodies oncology research is focused on the discovery, validation and development of novel therapeutic antibodies for the treatment of cancer. </li></ul>