Hallmarks of Neoplasm Flashcards
Sustaining proliferative signaling
- Oncogenes
- TKR
- Myc Genes
- can proliferate without external signal
Example for sustaining proliferative signaling
Breast Cancer
- ERBB gene amplification leads to overexpression of HER2 receptor resulting in increased cellular proliferation
- Not an error in the code, rather it is amplification of the gene
- Over expression of receptors on the cell
- Do have targeted therapy for this
Intervention for sustaining proliferative signaling
EGFR inhibitors
evading growth suppressors
- P53
- Speed bumps
- RB
- mutations in tumor suppressor
- most often mutations in transcription factors, cell cycle inhibitors, signal transduction, cell surface receptors, regulators of response to DNA damage
Example of evading growth suppressors
Pancreatic cancer
- MENIN gene mutation results in release of growth control due to diminished tumor suppressor function
- Will get tumors at other sites
intervention for evading growth suppressors
Cyclin dependent kinase inhibitors
Activating and invasion of metastasis
Alter epithelium
-Protection: need to have functioning junctions
-Glandular structure: secrete important fluids
Increases likelihood of getting into other tissues
-Can get lumps formed from altered glands and get randomly dispersed tissues
Example of Activating and invasion of metastasis
Breast cancer
-CDH1 gene mutation leads to loss of E Cadherin which enhances invasiveness
intervention for Activating and invasion of metastasis
Inhibitors of HGF/c Met
Enabling replicative immortality
- Preservation of DNA
- Telomerase
- cancer stem cells with unlimited replicative potential
example of Enabling replicative immortality
Uterine cancer
-Alterations in promoter of gene encoding telomerase reverse transcriptase (TERT) lead to protection of telomeres and increased cellular longevity
intervention for Enabling replicative immortality
telomerase inhibitors
Inducing angiogenesis
Trick host tissue into making more blood vessels
-tumors that are 1-2mm outgrow blood supply and need to induce this
example of Inducing angiogenesis
Renal cancer
-Mutations in VHL gene result in up regulation of expression of genes such as VEGF and PDGF whose products are involved in angiogenesis
intervention for Inducing angiogenesis
inhibitors of VEGF signal (bevacizumab- Avastin)
Resisting cell death
- Sabotage cell apoptosis pathway
- overexpression of antiapoptotic signaling molecules like Bcl-2
examples of Resisting cell death
Colon cancer
-Mutation in TP53 also result in degradation of apoptosis mechanisms in response to DNA damage
intervention for Resisting cell death
Pro-apoptotic BH3 mimetics
Deregulating cellular energetics
- Prefer aerobic glycolysis
- Perform glycolysis in an oxygen rich environment
- Results in metabolic building blocks in order to replicate
- Increase glucose receptors
- PET scan
example of Deregulating cellular energetics
Glycolytic fueling associated with activated oncogenes and mutated tumor suppressor genes
intervention for Deregulating cellular energetics
Aerobic glycolysis inhibitors
Avoiding immune destruction
- Immunogenic tumor cells may secrete immunosuppressive factors like TGF-Beta
- Tumor cells may recruit suppressive inflammatory cells such as regulatory T cells
example of Avoiding immune destruction
Shut down patrolling lymphocytes
intervention for Avoiding immune destruction
Immune activating anti-CTLA4 MAb
