Hallmarks of Neoplasm

Question 1

Sustaining proliferative signaling

Answer 1

• Oncogenes
• TKR
• Myc Genes
• can proliferate without external signal

Question 2

Example for sustaining proliferative signaling

Answer 2

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

Question 3

Intervention for sustaining proliferative signaling

Answer 3

EGFR inhibitors

Question 4

evading growth suppressors

Answer 4

• 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

Question 5

Example of evading growth suppressors

Answer 5

Pancreatic cancer

• MENIN gene mutation results in release of growth control due to diminished tumor suppressor function
• Will get tumors at other sites

Question 6

intervention for evading growth suppressors

Answer 6

Cyclin dependent kinase inhibitors

Question 7

Activating and invasion of metastasis

Answer 7

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

Question 8

Example of Activating and invasion of metastasis

Answer 8

Breast cancer

-CDH1 gene mutation leads to loss of E Cadherin which enhances invasiveness

Question 9

intervention for Activating and invasion of metastasis

Answer 9

Inhibitors of HGF/c Met

Question 10

Enabling replicative immortality

Answer 10

• Preservation of DNA
• Telomerase
• cancer stem cells with unlimited replicative potential

Question 11

example of Enabling replicative immortality

Answer 11

Uterine cancer
-Alterations in promoter of gene encoding telomerase reverse transcriptase (TERT) lead to protection of telomeres and increased cellular longevity

Question 12

intervention for Enabling replicative immortality

Answer 12

telomerase inhibitors

Question 13

Inducing angiogenesis

Answer 13

Trick host tissue into making more blood vessels

-tumors that are 1-2mm outgrow blood supply and need to induce this

Question 14

example of Inducing angiogenesis

Answer 14

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

Question 15

intervention for Inducing angiogenesis

Answer 15

inhibitors of VEGF signal (bevacizumab- Avastin)

Question 16

Resisting cell death

Answer 16

• Sabotage cell apoptosis pathway

- overexpression of antiapoptotic signaling molecules like Bcl-2

Question 17

examples of Resisting cell death

Answer 17

Colon cancer

-Mutation in TP53 also result in degradation of apoptosis mechanisms in response to DNA damage

Question 18

intervention for Resisting cell death

Answer 18

Pro-apoptotic BH3 mimetics

Question 19

Deregulating cellular energetics

Answer 19

• Prefer aerobic glycolysis
• Perform glycolysis in an oxygen rich environment
• Results in metabolic building blocks in order to replicate
• Increase glucose receptors
• PET scan

Question 20

example of Deregulating cellular energetics

Answer 20

Glycolytic fueling associated with activated oncogenes and mutated tumor suppressor genes

Question 21

intervention for Deregulating cellular energetics

Answer 21

Aerobic glycolysis inhibitors

Question 22

Avoiding immune destruction

Answer 22

• Immunogenic tumor cells may secrete immunosuppressive factors like TGF-Beta
• Tumor cells may recruit suppressive inflammatory cells such as regulatory T cells

Question 23

example of Avoiding immune destruction

Answer 23

Shut down patrolling lymphocytes

Question 24

intervention for Avoiding immune destruction

Answer 24

Immune activating anti-CTLA4 MAb

Question 25

Tumor-promoter inflammation

Answer 25

Inflammatory state also facilitates acquisition of hallmarks of cancer due to increased bioactive molecules

• Growth factors: enhance proliferation
• Survival factors: help avoid apoptosis
• Proangiogenic factors: stimulate angiogenesis
• ECM matrix modifying: stimulate angiogenesis, invasion, metastasis
• Inductive signals: help activate epithelial mesenchymal transition program

Question 26

intervention for Tumor-promoter inflammation

Answer 26

Selective anti-inflammatory drugs

Question 27

Genome instability and mutation

Answer 27

Single or cumulative genomic alterations enhances the acquisition of one or more of the hallmarks of cancer

Susceptibility to mutations occurs when defects occur in

• DNA damage sensors and repair activators
• DNA repair apparatus such as mismatch repair proteins
• Systems which inactivate or intercept mutagenic molecules before DNA damage can occur

Question 28

intervention for Genome instability and mutation

Answer 28

PARP inhibitors