Introduction to Cancer Definitions Naming Benign vs. Malignant Hallmarks of cancer

Define Neoplasm Abnormal growth of cells which persists after initial stimulus has been removed Or Cell growth which has escaped from normal regulatory mechanisms Is it benign or malignant? - Can be either!

Define Benign Neoplasm Cells which grow as a compact mass and remain at the site of origin

Define Malignant Neoplasm Growth of cells is uncontrolled Cells can spread to surrounding tissue and to distant sites

Define Dysplasia Pre-Malignant Condition Describes: Increased Cell Growth Altered Differentiation Cellular Atypia Common Sites = Cervix, Bladder, Stomach and Oesophagus Cervical Dysplasia can be caused by Human Papilloma Virus (HPV) Bladder Dysplasia – Urothelial Dysplasia which can lead to Transitional Cell Carcinoma

Define Differentiation The degree of similarity of tumour cells to the structure of the organ from which the tumour arose Well differentiated cancer cells look more like normal cells and tend to grow and spread more slowly (low grade)

How to Name a Neoplasm Originating Tissue Benign Malignant Bone Osteoma Osteosarcoma Smooth Muscle Leiomyoma Leiomyosarcoma Cartilage Chondroma Chondrosarcoma Fat Lipoma Liposarcoma Nerve Nurofibroma Neurofibrosarcoma Nerve Sheath Neurilemmoma Neurilemmosarcoma Fibrous Tissue Fibroma Fibrosarcoma Squamous Epithelium Papilloma Squamous cell carcinoma Transitional Epithelium Transitional cell carcinoma Glandular Epithelium Adenoma Adenocarcinoma Skin Melanocyte Naevus Malignant melanoma

Match each benign neoplasm with its connective tissue origin Bone Neurofibroma Smooth Muscle Lipoma Fat Osteoma Benign Connective Tissue Neoplasm always has the suffix = oma Exception to the rule = Glioma – as they are malignant Malignant Connective Tissue Suffix = Sarcoma Fibrous Tissue Leiomyoma Nerve Fibroma

Describe the Behaviour of Neoplasms Benign Malignant No invasion No metastasis Retains function Variable growth rate, often low Invades Metastasises Lose function Variable growth rate, may be high

Can you describe the Macroscopic differences of neoplasms Benign Malignant Capsule Well defined edge Ill-defined margin Haemorrhage Necrotic Centre

Can you describe the Microscopic differences of neoplasms Benign Malignant Low mitotic count, normal mitoses Retention of specialisation Organised Structural differentiation retained Low to high mitotic count, abnormal mitoses Loss of specialisation Unorganised Structural differentiation has wide range of changes

What are the 10 Hallmarks of Cancer? Oncology at a Glance, First Edition. Graham G. Dark. © 2013 John Wiley & Sons, Ltd. Published 2013 by John Wiley & Sons, Ltd.

10 Hallmarks of Cancer Mnemonic Immune System Evasion Invasion and Metastasis Inducing Angiogenesis Genomic Instability Tumour-promoting Inflammation Metabolism Reprogramming Sustaining Proliferative Signalling Replicative Immortality Resisting Apoptosis Growth Suppressor Evasion

What Happens First? Genomic Instability Metabolism Reprogramming Multistep genetic mutations occur, each enabling further clonal expansion of pre-malignant cells In cancer cells, the accumulation of mutations goes unchecked and therefore, these cells are more sensitive to mutagenic actions To sustain proliferation, cancer cells make adjustments to their energy production by: Reprogramming their glucose metabolism Upregulating glucose transporters such as glucose transporter 1 (GLUT1) Depending on alternate metabolic pathways

How Does It Survive? Sustaining Proliferative Signalling Growth Suppressor Evasion Healthy tissues regulate growth-promoting signaling pathways, which are responsible for driving progression of cells through the cell cycle. These signaling mechanisms are deregulated in cancerous cells. Tumour suppressors (Rb and TP53) halt cell cycle progression if excessive genome damage occurs Cancer cells are able to proliferate independantly of these signals

How Does It Survive? Replicative Immortality Tumour Promoting Inflammation Normal cells are able to divide a finite no. of times and then cell division is blocked Cancer cells overcome this by over-expressing telomerase, an enzyme that maintains telomere length, which protects the ends of chromosomes and allows the cell to continue proliferating. Tumour-associated inflammation may aid in tumour growth by supplying the tumour microenvironment with: Growth Factors Pro-Angiogenic Factors Survival Factors

How Does It Survive? Resisting Apoptosis Immune System Evasion All cancer cells dysregulate 2 signalling pathways by: Overexpressing anti-apoptotic proteins Silencing pro-apoptotic proteins Also resist cell death by altering normal cellular autophagy and necrosis Immune surveillance is an essential cellular process that proactively prevents tumor formation in the human body. Preclinical studies have suggested that an active immune system continuously recognizes and eliminates the vast majority of cancer cells before they establish themselves and form a tumor mass. However, cancer immunoediting, an emerging hallmark, includes 3 key phases — elimination, equilibrium, and escape. The immune system successfully recognizes and eliminates cancer cells, a process often described as the elimination phase. Tumor cells not eliminated by the immune system proceed to the equilibrium phase, in which the immune system controls cancer cell growth but does not completely eliminate the transformed cells. Tumor cells not susceptible to immune destruction progress into the escape phase. In this phase, the “escaped” tumor clones—not effectively detected and destroyed by the immune system—continue to divide and grow

How Does It Thrive? Infiltration of nearby blood and lymphatic vessels Invasion and Metastasis Inducing Angiogenesis Infiltration of nearby blood and lymphatic vessels Cancer cells are transported to non-contiguous tissues (forming metastatic lesions) Development of new blood vessels All cancers require a vascular network to supply nutrients and remove waste VEGF and PDGF are key players