TBL 8 - Neoplasia: Principles of tumor Pathobiology and Carcinogenesis Flashcards
(189 cards)
Describe a benign tumor.
Typically remains localized without destructive invasion or distant spread.
Describe a malignant tumor.
Typically invasive by nature and can spread to adjacent organs and/or distant tissues/ sites.
What is the definition of Hallmarks if Cancer?
A set of functional capabilities acquired by cells as they make their way from normalcy to neoplastic growth states.
Capabilities that are crucial for their ability to form malignant tumors.
What are proto-oncogenes?
Genes that encode normal cellular products involved in cellular growth and repair that, when over-expressed or form activating mutations, are converted to oncogenes.
What are some examples of genes that have point mutations, allowing them to have constitutive activation? (3)
K-RAS, EGF receptor, and BRAF
What are some examples of genes that become amplified or have over 2 copies of the coding DNA per cell? (6)
HER2, FGF3, MYC, CDK4, EGFR, and RAS
What are some examples of genes that are involved in translocation? (2)
BCL-ABL and EWS-FLI1
What are some examples of mechanisms leading to cancer gaining functional independence?
- Point mutations
- Gene amplification
- Aberrant over-expression
- DNA translocation
What happens when EGF (epidermal growth factor) receptor dimerizes?
1) Tyrosine phosphorylation
2) Cell proliferation due to HER2 over-expression
HER2: human epidermal growth factor receptor 2
What are some examples of HER-2 directed therapies? (5)
Trastuzmab, Lapatinib, Pertuzumab, Neratinib, Afatinib
What is B-Raf?
A proto-oncogene that is a downstream signal of RAS.
What would an activating mutation in BRAF cause?
Ras-independent activation of MAPK (MEK).
What is an example of a novel BRAF inhibitor?
Dabrafenib
What drugs worked better for patients: novel BRAF inhibitors or Ras targeting drugs?
Novel BRAF inhibitors
What is the normal function of PTEN?
1) Dephosphorylates PIP3 to PIP2
2) Antagonizes PI3K
3) Blocks AKT activation
PI3K: phosphoinositol 3-kinase
How can PTEN be silenced?
- Mutation
- Promotor hypermethylation
- Post-translational modification (ubiquitination and methylation)
What are MYC, c-JUN, c-FOS, and REL?
Transcriptional proteins
What does the transcriptional protein MYC impact when it undergoes amplification or translocation?
- Cell cycle progression genes like D cyclins
- Ribosomal RNA and metabolic reprogramming
- Up-regulation of telomerase and stem cell characteristics
What is NFkB?
A family of transcription proteins that have pro-cancer roles.
What do mutations in upstream NFkB effectors cause?
Activation of the NFkB pathway and then persistent activation of NFkB.
What is the retroviral oncogene v-Rel a homologue of?
It is a homologue of cRel which is one of the subunits if NFkB.
How are BRCA1 and the NFkB pathway connected?
Silencing of BRCA1 causes constitutive activation of the NFkB pathway.
What does persistent activation of the NFkB pathway cause?
- Abnormal cell proliferation and differentiation
- Enhanced metastasis
- Treatment resistance
What is an important role in cancer for NFkB?
Regulating the energy metabolism in cancer cells.