Neoplasia 3,4 (tbc)

1. Avoiding immune destruction
2. Evading growth suppressors
3. Enabling replicative immortality
4. Tumor promoting inflammation
5. Activating invasion and metastasis
6. Genomic instability (mutator phenotype)
7. Inducing angiogenesis
8. Resisting cell death
9. Deregulating cellular energetics
10. Sustaining proliferative signaling

1. Normal cell undergoes DNA damage
2. Failure of DNA repair causing mutation in the genome of somatic cells
3. If the mutation causes activation of growth promoting oncogenes or inactivation of tumour suppressor genes, it causes unregulated cell proliferation.
4. If the mutation causes alteration in genes that regulate apoptosis, it causes decreased apoptosis.
5. In both cases of unregulated cell proliferation and decreased apoptosis, it causes clonal expansion.
6. Angiogenesis (formation of new blood vessels) and escape from immunity along with additional mutations causes tumour progression.
7. The progression of the tumour causes a malignant neoplasm capable of invasion and metastasis.

1. Autocrine growth stimulation- abnormal expression of oncogenes (or receptors, proteins, transcription factors) or because of inactivation of tumour suppressor genes (that are supposed to inhibit growth pathways).
2. Reduced apoptosis- abnormal expression of genes which inhibit apoptosis (BCL-2)
3. Telomerase- repetitive DNA sequences at the end of a chromosome. Telomeric shortening causes restriction in the number of cell cycles. Telomerase prevents shortening.

Telomeres are repetitive DNA sequences at the end of a chromosome. Telomeric shortening causes restriction in the number of cell cycles. Telomerase prevents shortening of the telomeres which allows it to undergo further cell division.

1. Abnormal expression of oncogenes through their receptors/ signalling proteins/ transcription factors.
2. Inactivation of tumour suppressor genes (normally supposed to inhibit growth pathways)

Abnormal expression of genes which inhibit apoptosis (BCL-2 ).

It is a gene which inhibits neoplastic growth. For example, the TP53 gene is commonly mutated in cancer and it encodes for p53 protein.

It functions as a caretaker gene which repairs DNA damage and a gatekeeper gene that stops damaged cells from dividing (either by inhibiting proliferation or inducing apoptosis).

1. Mutations- missense (coding for a defective protein) or nonsense (unreadable gene)
2. Normal p53 forms complex with mutant and the normal protein gets inactivated.
3. p53 protein binds to oncoprotein encoded by the DNA viruses.

An oncogene is a gene which drives the neoplastic behaviour of cells and produce oncoproteins. It can be viral or just exist in normal cells.

1. Growth factors
2. Receptors for growth factors
3. Signalling mediator with tyrosine kinase activity- TSKs regulate cell survival and proliferation and are responsible signalling cascades.
4. Signalling mediator with nucleotide binding activity- involved in regulation of growth and proliferation

1. Additional chromosomes in the form of polyploidy (exact multiples of diploid state- 4n, 8n) or aneuploidy (inexact multiples)
2. Chromosomal translocations/ rearrangements These are called karyotypic abnormalities.

1. Telomerase expression induces immortalisation.
2. Inactivation of tumour suppressor gene function (p53, pRb) removes the growth inhibition.
3. Oncogene activation causes autocrine growth stimulation causing a neoplastic transformation.

An environmental agent which participates in causing tumours is a carcinogen. They are mutagenic and act on the DNA of the cells.

1. Epidemiological studies (accounting for confounding factors)
2. Occupational risks
3. Direct evidence (Chernobyl- observation of thyroid carcinoma in children)
4. Experimental testing (cell culture, animal testing, Ames test for mutagenicity on bacterial cultures)

Cause long lasting genetic damage, not sufficient to cause cancer – must be followed by a promoter

Require initiators to have caused damage, time period can vary after initiation

• One working gene is enough
• One faulty gene puts person at increased risk
• Two faulty mutated genes will result in a functional problem