Biology of Neoplasms PDF

# Biology of Neoplasms **MB Lecture 26** ## Objectives: By the end of this lecture the student will be able to: 1. Define neoplasia, neoplasms and oncology. 2. Recognize the main differences between benign and malignant neoplasms. 3. Nominate malignant neoplasms according to the tissue of origi...

# Biology of Neoplasms **MB Lecture 26** ## Objectives: By the end of this lecture the student will be able to: 1. Define neoplasia, neoplasms and oncology. 2. Recognize the main differences between benign and malignant neoplasms. 3. Nominate malignant neoplasms according to the tissue of origin. 4. Discuss in brief the mechanism and etiologic factors of cancer. 5. Enlist the biological criteria (Hallmarks) of neoplastic cells. 6. Explain the biological differences between normal cells and neoplastic cells. **MB Lecture 23** ## What Is Neoplasia/Neoplasm? * Neoplasia means: “abnormal new growth” * The tissue mass resulting from this abnormal new growth is called a 'neoplasm' or tumor. * Neoplasms result from uncontrolled proliferation of cells. * Oncology (Greek oncos = tumor) is the study of tumors or neoplasms. * Neoplasms are classified into: Benign & Malignant (cancer). **MB Lecture 23** ## Benign as Compared to Malignant * **Benign neoplasms:** Slower growth rate, non-invasive, don't metastasize. * **Malignant neoplasms (Cancers):** Faster growth rate, invasive, can metastasize. **MB Lecture 23** ## Biological Mechanisms of Cancer * Cancers arise from: 'Non-lethal genetic damage" or "Gene mutations". * Cancers are not the result of one single genetic change. * At least four to seven genetic changes are required for a normal cell to transform into invasive cancer. **MB Lecture 23** ## What causes the genetic changes that lead to cancer? * **Mutations can be:** * **A. Inherited gremline mutations** (rare familial cancer syndromes account for about 10% of cancers). * **B. Acquired Somatic mutations** (Majority of cancers; Sporadic): induced by exposure to environmental factors such as: * Physical agents: ultraviolet (UV) rays (sun exposure), X-rays (medical exposure) * Chemicals: tobacco products, dietary chemicals, and toxins * Infectious agents: bacteria and viruses. **MB Lecture 23** ## Examples of cancers arising from exposure to environmental factors: * UV rays --> skin cancers. Skin melanin protects skin. * Viruses: HPV (human papilloma virus) --> Cervical cancer, Hepatitis B virus --> Hepatic carcinoma. * Bacteria: Helicobacter pylori --> gastric carcinoma. * Chemicals --- * tobacco products --> lung cancer and urinary bladder cancer **MB Lecture 23** ## Cancer arises from single cells * A tumor is formed by the clonal expansion of a single cell that contains genetic damage (i.e., tumors are clonal) * Daughter cells contain the same abnormal DNA, and continue to divide and accumulate more DNA damage * Cancer hallmarks are produced by a series of mutations **MB Lecture 23,** ## Hallmarks of Cancer 1. **Independence = Self-sufficiency in growth signals:** * Normal cells need growth factor signaling to divide. * Cancer cells don't need growth factor signaling. They are independent cells → autonomous cell growth. **MB Lecture 23** ## 2. Resistance to anti-growth signals (mutated tumor suppressor genes) * Normally, tumor suppressor genes can inhibit the cell cycle (e.g., retinoblastoma gene, p53 gene). * In cancer cells, the antigrowth signals are disturbed, allowing continuous cell division. **MB Lecture 23** ## 3. Loss of contact inhibition: * Normal cells show contact inhibition; they divide to fill in a gap in the tissue, but they stop dividing when the gap is filled, and they contact each other. * Cancer cells continue to grow after they contact other cells causing a large mass of cells (tumor). **MB Lecture 23** ## 4. Unlimited replication: * Normal cells divide about 50-60 times, then loose the ability to divide. This is due to the shortening of telomeres (chromosome ends) with each cell cycle. When telomeres are markedly short, cells lose their ability to divide. * In germ cells, stem cells, & cancer cells, telomerase enzyme is activated, this enzyme elongates the chromosome ends allowing an unlimited number of cell divisions (immortality). **MB Lecture 23** ## 5. Resistance to cell death= Evasion of Apoptosis (mutated apoptosis genes) * Normal cells stop division and die by "apoptosis" in response to DNA damage. * Cancer cells resist death, evade apoptosis, and continue to divide, even when there is a large amount of damaged DNA or abnormal cells. **MB Lecture 23** ## 6.Sustained angiogenesis: * Like normal tissues, tumors need blood vessels to deliver oxygen and nutrients and remove waste products. * Tumor blood vessels are formed from the surrounding capillaries by a process called 'angiogenesis.” * Increased production of angiogenic factors such as vascular endothelial growth factor (VEGF) is important. * Angiogenesis helps in: * Tumor growth * Metastasis **MB Lecture 23** ## 8. Invasion and metastasis: * A. Invasion: Cancers grow by invasion of the surrounding tissue. * Invasion occur in three steps: * Loss of intercellular adhesion molecules, such as E-cadherins * Degradation of extracellular matrix by proteolysis. * Locomotion of cancer cells by pseudopodia. **MB Lecture 23** * B. Metastasis (mutations → metastatic sub-clones): * Metastases are secondary deposits of a malignant tumor located in distant tissues and organs. * Pathways of malignant tumor metastatic spread: * Three pathways: * Transcoelomic spread (Spread within body cavities), * Lymphatic spread, or * Hematogenous spread. * Cancer cells capable of metastasizing carry more mutations and are termed: metastatic sub-clones. **MB Lecture 23** ## Other hallmarks * Altered cellular metabolism * Evasion of the host immune response * Drug resistance **MB Lecture 23** ## Summary **Biological Criteria of a Cancer Cell** **Hallmarks of Cancer** - Self-sufficiency in growth signals - Insensitivity to antigrowth signals - Evading apoptosis - Loss of contact inhibition - Sustained angiogenesis - Rapid growth rate - Limitless replicative potential - Tissue invasion and metastasis ## Reference: Robbins & Cotran Pathologic Basis of Disease, 9e (Robbins Pathology), 2014 * ISBN-13: 978-1455726134 * ISBN-10: 1455726133 * Edition: 9th **MB Lecture 23** <br> This text describes a lesson taught in a medical biology class. It talks about the biology of neoplasms, defines the terms "neoplasia", "neoplasms" and "oncology", and describes the differences between benign and malignant neoplasms. The text also discusses the mechanisms of cancer development including genetic mutations, and describes the different types of mutations. It also covers the biological criteria (hallmarks) of neoplastic cells including independent growth, resistance to anti-growth signals, loss of contact inhibition, unlimited replication and evasion of apoptosis, as well as the pathways involved in angiogenesis and metastasis.