Cancer: A Detailed Study - PDF

Life Sciences I VF/AF/VM-U40 Cell biology Cancer Cell Biology  Cancer cells are cells that divide relentlessly, forming solid tumors or flooding the blood with abnormal cells. Cell division is a normal process used by the body for growth and repair. A parent cell divides to f...

Life Sciences I VF/AF/VM-U40 Cell biology Cancer Cell Biology  Cancer cells are cells that divide relentlessly, forming solid tumors or flooding the blood with abnormal cells. Cell division is a normal process used by the body for growth and repair. A parent cell divides to form two daughter cells, and these daughter cells are used to build new tissue or to replace cells that have died because of aging or damage. Healthy cells stop dividing when there is no longer a need for more daughter cells, but cancer cells continue to produce copies. They are also able to spread from one part of the body to another in a process known as metastasis. 2  History of the causes of cancer The earliest written record regarding cancer is from circa 1600 BC in the Egyptian Edwin Smith Papyrus and describes breast cancer.[ Hippocrates described several kinds of cancer, referring to them with the Greek word καρκίνος karkinos (crab or crayfish). This name comes from the appearance of the cut surface of a solid malignant tumor, with "the veins stretched on all sides as the animal the crab has its feet, whence it derives its name". Galen stated that "cancer of the breast is so called because of the fancied resemblance to a crab given by the lateral prolongations of the tumor and the adjacent distended veins". 738 Celsus translated karkinos into the Latin cancer, also meaning crab and recommended surgery as treatment. Galen (disagreed with the use of surgery and recommended purgatives instead. These recommendations largely stood for 1000 years. 3  History of the causes of cancer Hippocrates believed that the body had 4 humors (body fluids): blood, phlegm, yellow bile, and black bile. He suggested that an imbalance of these humors with an excess of black bile in various body sites could cause cancer. This was the humoral theory. After the humoral theory came the lymph theory. Stahl and Hoffman theorized that cancer was composed of fermenting and degenerating lymph, varying in density, acidity, and alkalinity. John Hunter, the Scottish surgeon from the 1700s, agreed that tumors grow from lymph constantly released from blood. Zacutus Lusitani (1575−1642) and Nicholas Tulp (1593−1674), doctors in Holland, concluded that cancer was contagious. Throughout the 17th and 18th centuries, some believed that cancer was contagious. 4 https://www.news-medical.net/health/Cancer-History.aspx  1838 that German pathologist Johannes Muller showed that cancer is made up of cells rather than lymph. Muller proposed that cancer cells developed from budding elements (blastema) between normal tissues. Rudolph Virchow (1821−1902), suggested that all cells, including cancer cells, are derived from other cells. He proposed the chronic irritation theory. He believed that cancer spread like a liquid. In the 1860s, German surgeon, Karl Thiersch, showed that cancers metastasize through the spread of malignant cells and not through a liquid. Until 1920’s trauma was thought to be the cause of cancers. 5  @IARC GLOBOCAN 2018 6 https://www.uicc.org/news/new-global-cancer-data-globocan-2018 7 There are different categories of cancer cell, defined according to the cell type from which they originate. Carcinoma, the majority of cancer cells are epithelial in origin, beginning in the membranous tissues that line the surfaces of the body. Leukaemia, originate in the tissues responsible for producing new blood cells, most commonly in the bone marrow. Lymphoma and myeloma, derived from cells of the immune system. Sarcoma, originating in connective tissue, including fat, muscle and bone. Central nervous system, derived from cells of the brain and spinal cord. Mesothelioma, originating in the mesothelium; the lining of body cavities. Leukaemia Myeloma Mesothelioma 8 Carcinoma Lymphoma Sarcoma https://my.clevelandclinic.org/health/diseases/4365-leukemia  Normal blood contains red blood cells, white blood cells and platelets. Leukemia cells outnumber normal cells in leukemia. 9 https://my.clevelandclinic.org/health/diseases/4365-leukemia Although there are >100 types of cancer, it has been proposed that there are six essential alterations in cell physiology that dictate malignant growth: self-sufficiency of growth signals, insensitivity to growth-inhibitory signals, evasion of apoptosis (programmed cell death), potential for limitless replication, angiogenesis, invasion and metastasis. 10  Cell Proliferation and Transformation In normal cells, cell growth and proliferation are under strict control. In cancer cells, cells become unresponsive to normal growth controls, which leads to uncontrolled cell division. Human cells require several genetic changes for neoplastic transformation. Cell type–specific differences also exist in the process by which a normal cell is transformed into a cancerous one. Abnormally proliferating, transformed cells outgrow normal cells in the culture dish (i.e., in vitro) and commonly display several abnormal characteristics. 11  Characteristics of Cancer Cells 12 https://ib.bioninja.com.au/standard-level/topic-1-cell-biology/16-cell-division/cancer-cells.html 13  Cancer Initiation Tumorigenesis is proposed to have three steps: initiation, promotion, progression. 14  Cell-Cycle Dysregulation in Cancer The proliferative advantage of tumor cells is a result of their ability to bypass a quiescent state. Cancer cells often show alterations in signal transduction pathways that lead to proliferation in response to external signals. Mutations or alterations in the expression of cell-cycle proteins, growth factors, growth factor receptors, intracellular signal transduction proteins, and nuclear transcription factors all can lead to disturbance of the basic regulatory mechanisms that control the cell cycle, allowing unregulated cell growth and proliferation. 15 Schematic representation of the phases of the cell cycle. Mitogenic growth factors can drive a quiescent cell from G0 into the cell cycle. Once the cell cycle passes beyond the restriction point, mitogens are no longer required for progression into and through S phase. The DNA is replicated in S phase, and the chromosomes are condensed and segregated in mitosis. In early G1 phase, certain signals can drive a cell to exit the cell cycle and enter a quiescent phase. Cell-cycle checkpoints have been identified in G1, S, G2, and M phases. CDK = cyclin-dependent kinase. Citation: Chapter 10 Oncology, Brunicardi F, Andersen DK, Billiar TR, Dunn DL, Kao LS, Hunter JG, Matthews JB, Pollock RE. Schwartz's Principles of Surgery, 11e; 2019. Available at: https://accessmedicine.mhmedical.com/content.aspx?sectionid=216204693&bookid=2576 Accessed: September 07, 2020 Copyright © 2020 McGraw-Hill Education. All rights reserved 16  Oncogenes Normal cellular genes that contribute to cancer when abnormal are called oncogenes. The normal counterpart of such a gene is referred to as a proto- oncogene. Oncogenes are usually designated by three-letter abbreviations, such as myc or ras. Oncogenes are further designated by the prefix “v-” for virus or “c-” for cell or chromosome, corresponding to the origin of the oncogene when it was first detected. More than 100 oncogenes have been identified. 17  Alterations in Apoptosis in Cancer Cells Apoptosis is a genetically regulated program to dispose of cells. Cancer cells must avoid apoptosis if tumors are to arise. The growth of a tumor mass is dependent not only on an increase in proliferation of tumor cells but also on a decrease in their apoptotic rate. 18  Autophagy in Cancer Cells Autophagy (self-eating) is a major cellular pathway for protein and organelle turnover. The autophagic pathway is a mechanism for the delivery of cellular materials to lysosomes for degradation. This process leads to the basal turnover of cell components and provides energy and macromolecular precursors. This process helps maintain a balance between anabolism and catabolism for normal cell growth and development. Autophagy plays an essential role during starvation, cellular differentiation, cell death, and aging. Autophagy is also involved in the elimination of cancer cells by triggering a nonapoptotic cell death program, which suggests a negative role in tumor development. Thus, in cancer, autophagy can have opposing and context-dependent roles, and interventions to both stimulate and inhibit autophagy have been proposed as possible anticancer treatments. 19  Cancer Invasion A feature of malignant cells is their ability to invade the surrounding normal tissue. Tumors in which the malignant cells appear to lie exclusively above the basement membrane are referred to as in situ cancer, whereas tumors in which the malignant cells are demonstrated to breach the basement membrane, penetrating into surrounding stroma, are termed invasive cancer. The ability to invade involves changes in adhesion, initiation of motility, and proteolysis of the extracellular matrix. 20  Angiogenesis Angiogenesis is the establishment of new blood vessels from a preexisting vascular bed. This neovascularization is essential for tumor growth and metastasis. Tumors develop an angiogenic phenotype as a result of accumulated genetic alterations and in response to local selection pressures such as hypoxia. Many of the common oncogenes and tumor-suppressor genes have been shown to play a role in the induction of angiogenesis. Angiogenesis is a prerequisite not only for primary tumor growth but also for metastasis. 21 https://www.sciencedirect.com/science/article/pii/S2090123217300644  Metastasis Metastases arise from the spread of cancer cells from the primary site and the formation of new tumors in distant sites. The metastatic process consists of a series of steps that need to be completed successfully. First, the primary cancer must develop access to the circulation through either the blood circulatory system or the lymphatic system. After the cancer cells are shed into the circulation, they must survive. Next, the circulating cells lodge in a new organ and extravasate into the new tissue. Next, the cells need to initiate growth in the new tissue and eventually establish vascularization to sustain the new tumor. 22 A schematic representation of the metastatic process. A. The metastatic process begins with an in situ cancer surrounded by an intact basement membrane. B. Invasion requires reversible changes in cell-cell and cell-extracellular matrix adherence, destruction of proteins in the matrix and stroma, and motility. C. Metastasizing cells can enter the circulation via the lymphatics. D. They can also directly enter the circulation. E. Intravascular survival of the tumor cells and extravasation of the circulatory system follow. F. Metastatic single cells can colonize sites and remain dormant for years as occult micrometastases. G. Subsequent progression and neovascularization leads to clinically detectable metastases and progressively growing, angiogenic metastases. (Reproduced with permission Steeg PS. Metastasis suppressors alter the signal transduction of cancer cells, Nat Rev Cancer. 2003 Jan;3(1):55-63.) Citation: Chapter 10 Oncology, Brunicardi F, Andersen DK, Billiar TR, Dunn DL, Kao LS, Hunter JG, Matthews JB, Pollock RE. Schwartz's Principles of Surgery, 11e; 2019. Available at: https://accessmedicine.mhmedical.com/content.aspx?sectionid=216204693&bookid=2576 Accessed: September 07, 2020 23 Copyright © 2020 McGraw-Hill Education. All rights reserved Exposure to particular substances have been linked to specific types of cancer. These substances are called carcinogens. 24  Chemicals Total recorded alcohol per capita Share of cancer deaths consumption (15+), in litres of pure alcohol. attributed to tobacco in 2016 Tobacco smoke, for example, causes 90% of lung cancer. 25 https://en.wikipedia.org/wiki/Alcohol_and_cance rhttps://en.wikipedia.org/wiki/Health_effects_of_tobacco#Cancer  Diet and exercise Diet, physical inactivity and obesity are related to up to 30–35% of cancer deaths. 26 https://hackneyjsna.org.uk/articles/lifestyle-behaviour/physical-activity/physical-activity-introduction/  Infection Worldwide approximately 18% of cancer deaths are related to infectious diseases. Some Viruses That Cause or Are Associated With Human Cancers 27 https://basicmedicalkey.com/cancer-an-overview/  Radiation Radiation exposure such as ultraviolet radiation and radioactive material is a risk factor for cancer. Fukushima Daiichi nuclear disaster Chernobyl radiation map from 1996 28 https://en.wikipedia.org/wiki/Radiation-induced_cancer  Hereditary Hereditary cancers are primarily caused by an inherited genetic defect. Less than 0.3% of the population are carriers of a genetic mutation that has a large effect on cancer risk and these cause less than 3–10% of cancer 29 https://www.massey.vcu.edu/cancer/family-history/genetic-counseling/types/  Hormones Some hormones play a role in the development of cancer by promoting cell proliferation. Insulin-like growth factors and their binding proteins play a key role in cancer cell proliferation, differentiation and apoptosis, suggesting possible involvement in carcinogenesis. Hormones are important agents in sex-related cancers, such as cancer of the breast, endometrium, prostate, ovary and testis and also of thyroid cancer and bone cancer. 30  Management of cancer: Surgery When used to treat cancer, surgery is a procedure in which a surgeon removes cancer from your body. Radiation Therapy Radiation therapy is a type of cancer treatment that uses high doses of radiation to kill cancer cells and shrink tumors. Chemotherapy Chemotherapy is a type of cancer treatment that uses drugs to kill cancer cells. Immunotherapy to Treat Cancer Immunotherapy is a type of cancer treatment that helps your immune system fight cancer. Targeted Therapy Targeted therapy is a type of cancer treatment that targets the changes in cancer cells that help them grow, divide, and spread. Hormone Therapy Hormone therapy is a treatment that slows or stops the growth of breast and prostate cancers that use hormones to grow. 31 https://www.cancer.gov/about-cancer/treatment/types Stem Cell Transplant Stem cell transplants are procedures that restore blood-forming stem cells in cancer patients who have had theirs destroyed by very high doses of chemotherapy or radiation therapy. Precision Medicine Precision medicine helps doctors select treatments that are most likely to help patients based on a genetic understanding of their disease. 32  Measures That Might Prevent Approximately 50% of Cancers if Introduced on a Population-Wide Basis https://basicmedicalkey.com/cancer-an-overview/ 33 AČIŪ UŽ DĖMESĮ www.lsmu.lt