Intro to cancer Flashcards
What is cancer?
- Cancer is a group of diseases
- Charachterised by abnormal cell growth through which cells may acquire potential to disperse (metastasise) from site of origin (primary tumour) to other sites in body(secondary tumours)
- Tumour growth id dependent upon delivery of nutrients and oxygen via incd vascular supply (angiogeneisis)
What are the different types of Tumour?
- Benign
- Malignant
What are benign tumours?
- Cells do not invade surrounding tissue - Do not metastasise
- Usually encapsualted - Restrains invasive capacity
- Can arise in any tissues; cells resemble those original tissue
- Cells well differentiated, slow growing
- For the most part, relatively harmless
What are Malignant tumours?
- Capable of intravasation, arrest at distant site and metastasis
- 85% carcinomas (epithelial cells), most others are sarcomas (Mesenchymal–connective tissue, fat, bone, etc)
- 3% are leukaemias and lymphomas - liquid tumours
- Cells poorly differentiated; Freq cell divisions–>Fast growing
- Leads to poor patient outcomes
What are the classifications of cancer pathology?
Carcinoma
* Most common type of cancer
* Arising from cells of embryonic endoderm or ectoderm
* Cover external and internal body surfacese.g. lung, breast, colon
Sarcoma
* Cancer arising from cells of embryonic mesoderm
* The supporting cells of body, bone, cartilage, fat, connective tissue and muscle
Lymphoma
* Cancer that arises in lymph nodes and tissues of bodies immmune system
Leukaemia
* Cancer of the immature white blood cells that grow in the bone marrow and accumulate in large numbers in blood stream
What are the causes of cancer?
- Tobacco
- Body weight
- Physical activity
- Diet
- Hormones
- Sunlight (UV)
- Occupational carcinogens
- Infectious agents (Viruses, Bacteria)
- Medical treatment
- Pollution
- Genetic factors
What are symptoms of cancer?
- Disease specific
- Often no symptoms in the early stages; but metastasis is early event
Lung cancer
* Cough haemoptysis (Coughing blood), chest pain, breathlessness and tiredness
Pancreatic cancer
* Weight loss, stomach or back pain, jaundice, development of diabetes
Breast cancer
* Lump or thickening (90% of such abnormalities are benign), change in breast size, discharge, bleeding, weight loss
What are mutations of cancer genes?
- Disruption of processes that control growth, location and mortality of cells contribute to development of tumours
-
Proto-oncogenes
* Encode aspects of signalling pathways that regulate proliferation
* Loss of function inc growth
2.Tumour suppressor genes
* Loss of function leads to dysregulation of cell cycle control, protein degredation, cell adhesion and motility
3.DNA repair enzymes
* Loss of function attenuates repair processes and genomic integrity
Explain diagram of cancer mutations
What makes a cell metastatic?
- Genetic mutations: Normal cell transforms into a cancer cell by accural of multiple genetic mutations over time
-
Mutagenic initiation
* Chemicals, radiation, viruses, spontaneous changes
* Incd Genome instability, positively selected -
Epigenetic alterations
* Acetuylation, methylation
What is Metastasis?
(The cascade) part 1
1.Migration – Cells move away from primary site and invade neighbouring tissue
2.Intravasation – Cells transmigrate across vessel wall barrier and enter circulation
* Enhanced by chronic inf, EC integrity loss, inc permeability
3.Survival – New microenvironment, shear forces from blood flow
* Only 1-4% of circulation tumour cells complete metastatic cascade
* Heterogenous pop of cells
* Heterotypic interactions with platelets - pro-metastatic role
* Selectins - Expressed by platelets and recognise carbohydrate moiety on cancer cells
* (Attach to cancer cells and protect them from immune responses and physical stress of blood vessel)
What is Metastasis?
(The cascade) part 2
4.Arrest at distant site - Cells have to avoid hostile blood or lymphatic flow forces and subsequently adhere stably to endothelial lining of target organs
* Endothelial fitness and crosstalk with CTCs might define final metastatic outcome
5.Extravasation - Cells transmigrate across vessel wall barrier and leave circulation
* Enhanced by chronic inf, EC integrity lost, incd permeability
6.Growth of secondary tumour
* Important role of angiogenesis
Explain the cascasde (diagram)
What are the hallmarks of cancer?
- Lifecycle of cancer?
- Sustaining proliferate signalling
- Evading growth suppressors
- Activating invasion and metastasis
- Enabling replicative immortality
- Inducing angiogenesis
- Resisting cell death
What are the emerging Hallmarks and enabling charchteristics of cancer?
Emerging Hallmarks
* Avoiding immune destruction
* Deregulating Cellular energetics
Enabling Characteristics
* Tumour-promoting inflammation
* Genome instability and mutation
What is angiogenesis?
- Cancr cells release a diffusible factor (tumour angiogenic factor) that stimulates blood vessels to grow towards it in order for it to include and maintain blood supply
What is angiogenesis (2)?
Normal process
* Development
* Menstural cycle
* Wound healing
* In response to ischaemic disease
Highjacked in cancer
* Requirement for tumour growt beyonf 1mm3
* Driven by incd metabolic demand and tissue hypoxia
What is normal angiogenesis?
- Formation of new blood vessels from pre-exiting vasculature, enabling vascularisation of prev avascular region
- Metabolically active tissues require constant supply of O2 and nutrients (need blood vessel within microns)
What is Dysregulated angiogenesis?
- Shares many characteristics with normal angiogenesis
- Pathological angiogenesis is persistent and unresolved
- Little stability and high cell turnover
- Vessel morphology
1. Poorly designed and distributed
2. Intrinsically leaky, lacking vasoconstrictor tone
3. ECs loosely connected with inadequate pericycle coverage
4. Vessel lumen is heterogenous mixture of endothelial and tumour cells
Compare normal vs Tumur angiogenesis.
Normal……….Tumour
Controlled……….Uncontrolled
Highly reg……….Unregulated
Organised……….Disorg
Mature……….Immature
Low interstitial pressure……….High interstitial pressure
Compare normal vs tumour blood vessels
(Diagram)
