Overview of Cancer Flashcards
What are the hallmarks of cancer and the therapeutic methods to target them?
Sustaining proliferative signalling - EGFR inhibitors.
Evading growth suppressors - Cyclin dependent kinase inhibitors.
Avoiding immune destruction - Immune activating anti-CTLA4 Mab.
Evading replicative immortality - Telomerase inhibitors.
Tumour promoting inflammation -
Selective antinflammatory drugs.
Activating invasion and metastasis - Inhibitors of HFG/c-Met.
Inducing angiogenesis - Inhibitors of VEGF signaling.
Genome instability and mutation - PARP inhibitors.
Resting cell death - Proapoptic BH3 mimetics.
Deregulating cellular energetics - Aerobic glycolysis inhibitors.
What are transformed 3T3 cells?
They are 3TC cells which are transfected by constitutive Ras to make them transformed. 3T3 cells are already immortal due to their loss of p19ARF or p53.
How are tumours named?
They are classified based on their embryonic tissue of origin.
Carcinomas - epithelial cells.
Adenocarcinoma - glandular tissue eg breast.
Sarcomas - connective tissue and muscle.
Leukemias - blood cell derived sarcomas.
What are benign tumours?
They resemble normal cells and tend to localised. They are often surrounded by a fibrous capsule and usually require little treatment. They can be surgically removed if appropriate.
What are malignant tumours?
They are less well differentiated than normal cells and grow and divide more rapidly. They have a high nucleus to cytoplasm ratio and fewer specialised structure. They are more difficult to treat and have less definition. They invade surrounding tissue and enter circulation when seeded at a different site - metastasis.
How are proto-oncogenes converted to oncogenes?
Proto-oncogenes normal function is to control cell growth. They are converted to oncogenes by gain of function mutation. Point mutation is always active, gene amplification - more protein, chromosomal translocation.
Oncogenes are genes which encode a protein able to transform cells , they are derived from normal cellular gene.
What are tumour suppressor genes?
Genes which restrain cell growth, promote cell death and DNA repair. When their function is lost it leads to excessive, unregulated growth of damaged cells. Recessive genes - both copies must be lost. There can be hereditary predisposition where the inheritance of a mutated copy of TSGene increases the tendency to develop cancer.
Transcription of tumour suppressor genes can be blocked by methylation of cytosine residues in promoter.
What are epigenetics?
Modifications to genomic and chromatin components/structure. They alter gene transcription and protein expression. They have heritable changes and usually involve histone modifications - methylation.
What is Knudoson Hyptothesis of cancer?
Cancer cells usually contain 3 to 7 mutations and cells undergoing a mutation must survive long enough to sustain subsequent mutations. Malignant transformation of a single cell is sufficient to give rise to a tumour. Any cell in a specific tissue is as likely to be transformed as any type of the same type. Benign tissue surrounded by malignancy frequently contains all but one of these mutations.
What are the risk factors of cancer?
Lifestyle - environment, job.
Smoking accounts for 40% of cancer deaths. Tobacco smoke contains 81 carcinogens.
UV, radiation exposure.
Diet -
Eastern diet increased risk of stomach cancer over western diet.
Mediterranean diet is the best.
Reproductive life -
Nuns have a higher risk of breast cancer but lower risk of cervical cancer.
Where do tumours usually result from?
Activation of immune system and inflammation. The tumour microenvironment is important.
