Cancer- Intro Flashcards
What is Cancer?
Cancer is a group of diseases which are characterised by uncontrolled cell growth, multiplication and spread within the body, of abnormal forms of the body’s own cells
What is the medical term for Cancer?
Neoplasm = new growth
Almost all cancers are clones of cells which arise from one mutated cell
What mechanisms are different in cancer cells?
The normal regulatory mechanisms that control growth and multiplication have been lost or changed
New cells form when the body doesn’t need them
What special characteristic do cancer cells lack?
Special characteristics that distinguish one type of cell from another e.g. liver cell from a blood cell
Cancer cells tend to be poorly differentiated
What do the extra cells in cancer form?
a mass of tissue called a tumour
can be benign or malignant
What’s the difference between benign and malignant tumours?
Benign:
- Rarely life threatening
- Do not invade neighbouring tissues
- Does not spread to other parts of the body
Malignant:
- May be life threatening
- Can invade nearby organs and tissues
- Can spread (metastasis)
What is metastasis?
Cancer cells from the original (primary) tumour grow and/or move to invade neighbouring tissues
If these tissues contain blood or lymphatic vessels, some cancer cells can break away from the primary tumour, enter circulatory system and travel through the body
The cancer cells that break away and enter the circulatory system, what do they form?
Reinvade tissue at new location and grow
Produces secondary tumours
The cells are the same from the same primary tumour
What are the different ways of naming types of Cancer
- Refer to the site of primary tumour
- Named after the person who discovered it
- According to the primary tissue from which they arose
What are the most common cancers in the UK?
Breast, lung, large bowel, and prostate cancers (54%)
What is the incidence of cancer by age?
63% in people aged 65+
36% in 75+
What is cancer prevalence?
Refers to the number of people who have previously received a diagnosis and who are still alive at a given point
Both incidence and survival pattern
How do most cancers arise?
Most cancers arise spontaneously
It is caused mostly by mutations in the genes of individual cells
However, many factors influence it’s rate of occurrence
What are the causes of some cancers attributed to?
(A) Lifestyle + environmental factors- smoking, diet, sunlight/ UV exposure, occupation
(B) Viruses- cause of 15% of cancers
(C) Inherited genetic mutations
(D) Hormonal factors
What are carcinogens and mutagens?
Carcinogens are substances or radiation types that directly cause cancer, most act by mutating DNA
A compound that reacts with DNA and somehow changes the genetic makeup is a mutagen
Are all cancers avoidable?
No, in many cases it seems that cancers develop simply due to the unavoidable accumulation of mutations in aging cells
What are the 2 main categories of genetic change that gives rise to cancer?
- The activation of proto-oncogenes to oncogenes
- The inactivation of tumour suppressor cells
What are somatic mutations?
They arise in a single cell in a developing or adult organism and are not inherited in germline
When are mutations most dangerous?
If these mutations occur in a cell that is about to die, it is very unlikely to be dangerous
Mutations are most dangerous in stem cells, healthy stem cells give rise to many new cells
What are oncogenes and tumour suppressors?
Mutations in genes can turn normal cells into cancer cells
Oncogenes are genes that drive cancer when they are turned on too much
Tumour suppressors do this when turned off or are lost
What are proto-oncogenes?
Normal genes which in healthy cells code for proteins involved in control of cell division, cell death
Oncogenes arise from mutated proto-oncogenes
What do oncogenes do?
Are either more active than their corresponding proto-oncogene or active at inappropriate times
Some oncogenes stimulate uncontrolled cell proliferation
What are the different ways a proto-oncogene can become an oncogene?
- Point mutation
- Gene amplification
- Chromosomal translocation
How do point mutations give rise to cancer?
Point mutations can occur within the protein coding sequences, changing the protein to be more active
Can also occur in control regions of a gene, leading to more protein production
Increased protein (onco-proteins) production drives cancer
What is an example of a proto-oncogene subject to point mutation?
PIK3CA
The PIK3CA gene encodes the catalytic subunit of the enzyme PI3-kinase
PI3-kinase is a lipid kinase that phosphorylates a lipid to signal cell growth
What is the TP53 gene?
Encodes the tumour supressor P53
P53 is a transcription factor which causes cells to stop growing and/or die when cells are stressed and damaged
What growth signal is usually overactivated in most tumours?
The lipid PIP3
How does gene amplification give rise to cancer cells?
Over expression of a gene can make a proto-oncogene behave like an oncogene
Any problems with DNA damage in cancer genome = multiple copies of genes leading to increased protein production
What are the examples of gene amplifications in different cancers?
MYC in leukemias
K-RAS in colon cancer
HER2 in breast cancer
What is an example of gene amplification in breast cancer?
HER2- defines sub type (20%) of breast cancer
Means extra copies of HER2 gene, much more HER2 protein HER2 encodes receptor for growth factors
What is chromosomal translocation?
Brings together two previously unlinked segments of the genome together. Large scale genomic rearrangement
Happens sometimes when DNA damage repair joins incorrect chromosome fragments together
How does chromosomal translocation result in cancer?
- synthesis of a new fusion protein
OR - inducing inappropriate expression of a protein
What is the Philadelphia chromosome?
Chronic Myeloid Leukemia’s are caused by a translocation between chromosomes 9 and 22
Results in a fusion gene bcr-abl wbich codes for an unregulated fusion-protein tyrosine kinase which doesn’t exist in normal cells
What happens in Burkitt’s lymphoma?
a translocation is seen involving chromosome 8 and three other chromosomes (2,14,22)
In this case a fusion protein isn’t produced
This results in over-expression of the MYC protein
What do Tumour Supressor genes code for?
code for proteins that the normal function of which makes cancer less likely
e.g. proteins that function as negative regulators of cell proliferation or survival
What happens if tumour suppressor genes become mutated or inactivated?
cell transformation can take place
such cells can progress to cancer, usually in combination with other genetic changes
What role do alleles play in tumour suppressor genes?
in some cases, both alleles (gene copies) that code for a tumour suppressor gene must be mutated or inactivated before an effect can take place, i.e they are recessive
What is an example of a tumour suppressor protein?
p53 are involved in detecting damage in a cells DNA and blocking its replication
i.e preventing mutations passing on
If the DNA cannot be repaired then p53 promotes apoptosis
Most cancers have mutations in p53
What does the p53 protein do?
The p53 protein is a DNA binding transcription factor which when undamaged and activated binds to the promoter sequences of genes to switch on their expression
These sets of genes are those involved in growth arrest and apoptosis
What is the most frequent event leading to cancer in humans?
Mutation of the tumour suppressor gene: TP53 which codes for the protein p53
In normal cells how does the p53 protein work?
A DNA damaging checkpoint, requiring the p53 protein, prevents a cell from the completing the cell cycle if it’s DNA is damaged or the cell has suffered other types of damage
What % of cancers harbour a TP53 mutation and have no functioning p53 protein?
50% of human cancers
What are inherited vs sporadic cancers?
Most cancers are sporadic, arise at random or caused by environmental factors, random mutation
Some people inherit an elevated risk of cancer. In this case a high risk cancer gene is inherited in all cells of the body. It is usually a damaged copy of a tumour suppressor gene