Tumour Biology part 2 Flashcards
What are the different types of screening ?
Physical exam and history: to check warning signals and patient’s habits and past illnesses and treatments.
- Laboratory tests: samples of tissue, blood, urine, or other substances in the body.
- Imaging procedures: Procedures that make pictures of areas inside the body. •
Genetic tests: Tests that look for certain gene mutations (changes) that are linked to some types of cancer.
What is Biopsy ? (Hyperplasia)
Reversible tissue growth based on an excessive rate of cell division.
Normal tissue response to an irritating stimulus (e.g. callus).
Cell structure and arrangement within the tissue remain normal
What is Biopsy (dyperplasia )
Abnormal type of excessive cell proliferation characterized by loss of normal tissue arrangement and cell structure.
Often reversible but occasionally malignant
Carcinoma in Situ
Most severe cases of dysplasia: carcinomas in situ.
dysplasia: carcinomas in situ.
Mild dysplasia
Carcinoma in situ (severe dysplasia) Cancer (invasive)
Normal Hyperplasia
Uncontrolled growth of cells that remains in the original location but may metastasize.
Tumour staging
Staging is based on tumor size, invasion of surrounding tissues, and metastasis to lymph nodes or other parts of the body.
What causes Cancer?
The change in risk for cancer for Japanese families could involve cultural, behavioral, or environmental factors predominant in one location and not in the other.
Tobacco is responsible for 30 % of death
Main cause of lung cancer but also contributes to cancer of the mouth, larynx, esophagus, stomach, pancreas, kidney, and bladder.
Responsible for one out of every three cancer deaths, the largest single cause of death from cancer.
Viruses
Some of the viral genetic information is inserted into the chromosomes of the infected cell, and this causes the cell to become malignant.
Liver cancer - Hepatisis B Virus
Usually caused by persistent infections
Cancer develops rarely, usually many years after infection
Virus infection is only one link of a complex chain of reactions.
HIV infections ?
HIV immune suppression makes people susceptible to KSHV infection (Kaposi’s sarcoma-associated herpesvirus), which stimulates Kaposi’s sarcoma, a malignant tumor of blood vessels located in the skin
Inheritance
80-90% percent of cancers occur in people with no family history of the disease. However, certain kinds of inherited genetic alterations can increase an individual’s susceptibility to develop cancer
What is a gene promoter ?
A DNA sequence that initiates the transcription of a gene
Proto-oncogenes
Genes that promote cell growth, differentiation or mitotic activity.
A mutation, amplification or translocation to another chromosome could lead to oncogene activation
An epigenetic change (i.e. DNA methylation) could also lead to oncogenic activation
What are Oncogenes?
Oncogenes are genes whose PRESENCE in certain forms can stimulate the development of cancer.
What are Tumour Suppresor genes ?
Tumor suppressor genes are normal genes whose ABSENCE can lead to cancer: they slow down cell growth and division.
Inherited defect in one gene copy will not lead to cancer because the other normal copy is still functional, but it increases the risk of developing cancer.
p53 – The guardian of the genome
One particular tumor suppressor gene codes for a protein called “p53” that can trigger cell suicide (apoptosis).
In cells that have undergone DNA damage, the p53 protein acts like a brake pedal to halt cell growth and division.
If the damage cannot be repaired, the p53 protein eventually initiates cell suicide, thereby preventing the genetically damaged cell from growing out of control.
DNA Repair Gene
DNA repair proteins correct errors that arise when cells duplicate their DNA prior to cell division. Mutations in both copies of DNA repair genes lead to a failure in repair, allowing subsequent mutations to accumulate.
What does Cancer involve ?
Cancer tends to involve multiple mutations affecting different aspects of the cell biology of the tumor: tissue invasion and metastasis, angiogenesis, apoptosis evasion, etc.
What doe Cancer involve ?
Cancer Tends to Involve Multiple Mutations
Cancer Tends to Involve Multiple Mutation
Malignant cells invade neighboring tissues, enter blood vessels, and metastasize to different sites
More mutations, more genetic instability, metastatic disease
Proto-oncogenes mutate to oncogenes
Mutations inactivate DNA repair genes
Cells proliferate
Mutation inactivates suppressor gene
Benign tumor cells grow only locally and cannot spread by invasion or metastasis
Apoptosis ? - Programmed Cell death
Cell suicide
Cancer angiogenesis
Tumours derive blood supply from the tissues they invade.
If a malignant tumour overgrows its own blood supply: necrosis
They also induce angiogenesis to maintain their demands
Oncogene Addiction ?
Cancer cells contain multiple genetic and epigenetic abnormalities.
Despite this complexity, their growth and survival can often be impaired by the inactivation of a single oncogene. This phenomenon is called “oncogene addiction”.
Combination therapy may also be required to prevent the escape of cancers from a given state of oncogene addiction.
Orthogonal Cancer Therapies
A tumor consists of genetically distinct subpopulations of cancer cells, each with its own characteristic sensitivity profile to a given therapeutic agent.
Each cancer therapy can be viewed as a filter that removes a subpopulation of cancer cells that are sensitive to this treatment while allowing other insensitive subpopulations to escape.
By combining therapies with orthogonal modes of action, a combinatorial filter can be set up to prevent tumor recurrence
