Cell Biology Lecture: Hallmarks of Cancer (2024-2025 S1) PDF

Introduction to Carcinogenesis Non-Hodgkins lymphoma Radiolabeled fluorodeoxyglucose (FDG) PET Scan Figure 20-1 Molecular Biology of the Cell (© Garland Science 2008) Carcinogenesis: Introduction Impact of cancer Some definitions Hallmarks of Cancer Lite...

Introduction to Carcinogenesis Non-Hodgkins lymphoma Radiolabeled fluorodeoxyglucose (FDG) PET Scan Figure 20-1 Molecular Biology of the Cell (© Garland Science 2008) Carcinogenesis: Introduction Impact of cancer Some definitions Hallmarks of Cancer Literature: Hallmarks of Cancer: The Next Generation (Cell 2011, 144, pg 646- 654 left column) MBC 6th Edition, chapter 20 1091-1126  Some, not so nice, numbers There were an estimated 2.7 million new cases of cancer and 1.3 million deaths from cancer in Europe in 2022. The most common cancer sites were cancers of the female breast, followed by colorectal, prostate and lung cancer. The most common causes of death from cancer were cancers of the lung, colorectal, breast and pancreatic cancer. https://ecis.jrc.ec.europa.eu/factsheets_2022.php Cancer is an age-related disease From NIH.gov Incidence breast cancer Breast cancer  Cancer survival increases Cancer.org, on 03-09-2019 For most cancers survival improved! 5-year survival rate in percentages Average of all cancer Skin cancer Breast cancer Colon cancer Lung cancer Pancreatic cancer  Some definitions Benign tumor: neoplastic cells remain clustered together in a single mass (neoplasm means a relentlessly growing mass of abnormal cells) Malignent tumor: considered as cancer cells have acquired the ability to invade surrounding tissue http://www.web-books.com/eLibrary/Medicine/Cancer/09MB9.html 03-09-2019 Some definitions Leukemia – cancer arising from white blood cells Lymphoma – cancer arising from the lymph nodes Carcinomas: cancer arising from epithelial cells Sarcomas: cancer arising from connective tissue or muscle cells Invasiveness: – implies an ability to break loose, enter the bloodstream or lymphatic vessels and form secondary tumors, called metastases, at other sides in the body Metastasis: − malignant tumors give rise to metastases How many mutations are necessary to transform normal cells into cancerous cells? mutations gene deletion, amplification or rearrangements epigenetic changes viral integration Six changes are needed to cause cancer  Most prominent feature is: Hallmarks of Cancer: The Next Generation Cell Volume 144, Issue 5 2011 646 - 674 http://dx.doi.org/10.1016/j.cell.2011.02.013 Removal of the brake: The importance of P53: Unlimited replicative potential: The importance of telomeres  Tumours need food! Tumour-associated neovasculature VEGF Loss of adhesion molecules:  Cellular causes for cancer development Proliferation, Cell cycle overactivity of angiogenesis, arrest, underactivity of growth- invasion apoptosis growth- promoting inhibitory events: events: e.g. Growth e.g. DNA repair, factor cell cycle arrest, signaling, apoptosis transcription of proliferation factors Can lead to cancer development The cancer genes Oncogenes Mutated overactive forms of genes that cause normal cells to grow Mutation of one allele can lead to overactivity Growth factors, e.g. (EGF) Growth factor receptors, e.g. (EGF-R) Signal transducers, e.g. ras, -catenin Transcription factors, e.g. c-myc Programmed cell death regulators, e.g. bcl1 Extracellular matrix regulation, e.g. (integrins, metalloprotease) Tumor suppressor proteins Tumor suppressors have anti-proliferative function Loss of function by mutation of both allelles can lead to cancer If mutated tumor suppressor acts in a dominant-negative fashion, mutation of one allel is sufficient to disturb cellular balance. – Proteins that regulate transcription factors, e.g. Rb1, VHL, APC,BRCA1 – Proteins that repair DNA, e.g. (BRCA2) – Cell “suicide” genes, e.g. p53, p21 – Signal transducer, e.g. LKB1 Figure 3 Emerging Hallmarks and Enabling Characteristics An increasing body of research suggests that two additional hallmarks of cancer are involved in the pathogenesis of some and perhaps all cancers. One involves the capability to modify, or reprogram,... Douglas Hanahan , Robert A. Weinberg Hallmarks of Cancer: The Next Generation Cell Volume 144, Issue 5 2011 646 - 674 http://dx.doi.org/10.1016/j.cell.2011.02.013 Understanding the Warburg effect (emerging hallmark deregulating cellular energetics): Evading immune destruction (emerging hallmark): Anti-tumor immunity is a significant barrier to tumor formation and progression. -> the new therapies in treating cancer! Enabling characteristic, tumour promoting inflammation First thought action of the immune system to battle cancer. Inflammation provide bioactive molecules for growth, angiogenesis, survival. Tumour microenvironment.  Enabling characteristic increased rate of mutation: breakdown genomic maintenance machinery compromising surveillance systems Figure 6 Therapeutic Targeting of the Hallmarks of Cancer Drugs that interfere with each of the acquired capabilities necessary for tumor growth and progression have been developed and are in clinical trials or in some cases approved for clinical use in t... Douglas Hanahan , Robert A. Weinberg Hallmarks of Cancer: The Next Generation Cell Volume 144, Issue 5 2011 646 - 674 http://dx.doi.org/10.1016/j.cell.2011.02.013