DEFINITIONSNAMING

BENIGN VS. MALIGNANTHALLMARKS OF CANCER

Introduction to 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

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)

Benign Malignant

No invasion No metastasis Retains functionVariable growth

rate, often low

InvadesMetastasises Lose functionVariable growth

rate, may be high

Describe the Behaviour of Neoplasms

Benign Malignant

CapsuleWell defined edge

Ill-defined marginHaemorrhageNecrotic Centre

Can you describe the Macroscopic differences of neoplasms

Benign Malignant

Low mitotic count, normal mitoses

Retention of specialisation

OrganisedStructural

differentiation retained

Low to high mitotic count, abnormal mitoses

Loss of specialisation

UnorganisedStructural

differentiation has wide range of changes

Can you describe the Microscopic differences of neoplasms

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

Genomic InstabilityMetabolism 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

What Happens First?

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 ImmortalityTumour 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:1. Overexpressing anti-

apoptotic proteins2. Silencing pro-apoptotic

proteins Also resist cell death by

altering normal cellular autophagy and necrosis

How Does It Survive?

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

How Does It Thrive?