Lecture 2 Flashcards
WHAT IS CANCER?
a disease of unregulated growth of cells resulting from genetic mutations
Not a single disease but a generic/umbrella term for a large family of diseases that can affect any part of the body.
Definition: a disease caused by an uncontrolled division of abnormal cells in a part of the body.
* Usually fatal if untreated
Cancer cells are abnormal in many ways
- in the way they multiply indefinitely
- how they invade underlying tissue
- migrate to other sites of the body and multiply there
Cancer causes death because
the cells proliferate continuously and don’t die at the same rate as normal cells, crowding out healthy cells and causing disruption to normal function
- 2018 – 18 million diagnoses , 9.6 million deaths
- Up to 50% of the population will get cancer at some stage of their life.
Neoplastic diseases:
Normal life processes are characterized by continuous growth and maturation of cells, and all cells are subject to control mechanisms that regulate their growth rate.
- In contrast, Neoplasm (Neo =new + plasm=growth) is an overgrowth of cells that serve no useful purpose; for example a tumour
A benign tumour (neuroma) arises from the siatic nerve. Note No infiltration of the adjacent nerve
CLASSIFICATION OF TUMOURS
Benign tumor
-small
slow growing
non invasive
well differentiated
stay localized (stay where they are and can’t invade or metastasize)
Malignant Tumor
large
fast-growing
invasive
poorly differentiated
metastasize (infiltrate, invade, destroy surrounding tissue and metastasize to other parts of body)
Cancers are usually described by
a) the location in the body from which they originated in;
b) the type of cell from which they originate (as many organs are composed of multiple types of tissue)
Polyp, papiloma
Any benign tumour projecting from surface epithelium.
Adenoma (adeno- gland )
benign tumour of epithelial tissue with glandular origin; often from glandular organs, including the adrenal glands, pituitary
gland, thyroid, prostate
Carcinoma
Malignant tumor arising from surface, glandular or parenchymal epithelium (but not endothelium or mesothelium) approx. 90% of human cancers
Sarcoma
Malignant tumour of mesenchymal, connective tissue eg bone, cartilage, fat, muscle, vascular, or hematopoietic tissues
Leukemia
Neoplasm of blood cells
TYPES OF CANCERS
Carcinomas
(cells that cover internal and
external body surfaces)
TERATOMA
A tumour of mixed cell components
Often arise in the reproductive tract
May consist of fat, muscle, bone, hair and oil
E.g. Dermoid cyst: A common benign cystic tetratoma that commonly arises in the ovary
HALLMARKS OF CANCER
- Self-sufficiency in growth signals 2. Insensitivity to anti-growth signals 3. Evading apoptosis
- Limitless replicative potential
- Sustained angiogenesis
- Tissue invasion and metastasis
Updated in 2011 to include 2 new Hallmarks
1. Deregulated metabolism
2. Evading the immune system
CANCER CELL DIVISION
Normally, cell divisions are strictly controlled. Require signaling from growth factor receptors to proliferate and will undergo a controlled form of cell death (apoptosis) when this signaling ceases or in response to DNA damage
In cancer cells, mutations have removed these controls and allows for the cells to continually grow out of control
– They may not detect neighbouring cells
– They may produce their own growth hormones to stimulate cell division
– They may not produce tumour suppressor proteins
– They ignore normal apoptotic processes
GROWTH OF CANCER CELLS
Cancer cells can divide every 2-6 weeks
This is a rough estimate and can vary significantly between different tumor types and different patients
Tumuor size
One million cancer cells = head of a pin One billion cancer cells = a small grape
If cancer cells divide every month, it would be 2.5 years before one cancer cell grows into a small grape-sized tumor.
cancer
- a person has usually had cancer for several years before it is detected and/or causes side effects.
Multiple genetic changes required for full development of cancer – can take several years to accumulate
- Often results in gradual changes to the cells structure, shape and biological behaviour
- Often undergoes changes including hyperplasia (increased cell growth) and dysplasia (disorderly growth)
- Development of a small localised tumour called “carcinoma in situ” can then develop. Although not usually dangerous, these in-situ tumours can progress to malignant, aggressive tumours.
ONCOGENESIS
Transformation of normal cells into cancer cells is referred to as tumourigenesis, carcinogenesis or oncogenesis
Multi-step process, entailing changes in the expression of many genes. Commonly mutated genes include both tumuour suppressors (genes which work to reduce development of cancer) and oncogenes (genes that promote cancer once mutated)
Cancer risk increases with age. Two main theories currently exist to explain this findings
: -Conventional oncogenesis
-Adaptive oncogenesi
CONVENTIONAL ONCOGENESIS MODEL - Conventional View :
Aging primarily contributes to increased cancers by facilitating the accumulation of oncogenic mutations (red cells), including activating mutations in oncogenes or genetic/epigenetic inactivation of tumor suppressor genes.
as we age the risk of cancer increases.
More than 80% of human cancers being diagnosed after the age of 50, aging represents the single most important prognostic factor for many cancers, including lung, breast, colon, prostate, and certain leukemias
INVASION
When cancer cells spread (no longer benign) from the primary site to another part of the body Complex process involving change of cells to a migratory phenotype and secretion of enzymes to break down surrounding ECM
Metastasis
Tumour cells are transported through the circulatory system
Cancer migrate to particular locations within the body including the bone, liver, brain, lungs and lymph nodes, where they may form secondary/tertiary tumours
Most people who die of cancer die of metastatic disease. Prognosis declines significantly the greater the spread of the metastasis
TUMOUR ANGIOGENESIS & NECROSIS
As a tumour develops it requires oxygen and nutrients for survival. As a tumour enlarges the centre of the tumour may not receive enough nutrients, forming a necrotic core
Cancers often secrete signaling factors (e.g. VEGF) to induce nearby blood vessels to grow towards them to continue supplying oxygen and nutrients.
This process is known as angiogenesis and can be inhibited with anti-angiogenic therapy to try and limit blood supply to the tumuor
Skin cancer
- Usually keratinocyte or melanocyte based tumours
- Often divided into melanoma and non- melonoma
Nevus
a benign tumour of melanocytes, often called a mole
Melanoma
malignant tumour of melanocytes
basal cell carcinoma
Accounts for approximately 75% of all skin cancers.
This highly treatable cancer starts in the basal cell layer of the epidermis (the top layer of skin) and grows very slowly.
Basal cell carcinoma usually appears as a small, shiny bump or nodule on the skin - mainly those areas exposed to the sun, such as the head, neck, arms, hands, and face.
It commonly occurs among persons with light-colored eyes, hair, and complexion.
squamous cell carcinom
Accounts for about 20% of all skin cancer cases. Although more aggressive than basal cell carcinoma, this cancer is highly treatable. Squamous cell carcinoma, may appear as nodules or red, scaly patches of skin, and may be found on the face, ears, lips, and mouth. Squamous cell carcinoma can spread to other parts of the body. This type of skin cancer is usually found in fair-skinned people
malignant melanoma
-less common, this type of skin cancer is the most deadly,
-79% of all skin cancer deaths
. Malignant melanoma starts in the cells that produce pigment in the skin. Malignant melanoma usually begins as a mole that then turns cancerous
.
This cancer may spread quickly. Malignant melanoma most often appears on fair-skinned men and women, but persons with all skin types may be affected.
LUNG CANCER
1 cause of cancer deaths worldwide
- Lung cancers can arise in any part of the lung, but 90% to 95% of cancers of the lung are thought to arise from the epithelial cells, the cells lining the larger and smaller airways (bronchi and bronchioles), for this reason, lung cancers are sometimes called bronchogenic carcinomas.
- Cancers also can arise from the pleura (called mesotheliomas) or rarely from supporting tissues within the lungs, for example, the blood vessels.
