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Flashcards in Lecture 5 Deck (26)
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1
Q

examples of “macro” differences in cancer cells vs normal cells

A

– Proliferative rates
– DNA synthesis rates
– Ineffecient repair of damage

2
Q

Possible novel targets of chemotherapeutics

A
– Signal transduction
– Angiogenesis
– Evasion of apoptosis
– Immune tolerance
– Cell Cycle dysregulation
– Tissue invasion and
metastasis
3
Q

Abberant expression of growth receptors and /or mutated signal transduction elements related to:

A
– potential for proliferation, invasion, metastasis
– angiogenesis
–Shortened survival of patients
–Poor response to standard chemotherapy
–Poor prognosis
4
Q

Main mediator of cell signaling (what surface protein?)

A

receptor tyrosine kinase

5
Q

Changes in receptor kinase proteins causes what 3 consequences?

A

–Overexpression of RTK protiens
–Functional alterations caused by mutations in the corresponding genes. Gain of function
–Abnormal stimulation by autocrine growth factor loops. Increased stimulation

6
Q

Primary targeted RTKs

A

–EGFR-HER-2 family (epidermal growth factor receptor)
–C-Kit (proto-oncogene coding for an RTK)
–VEGFR‘s (vascular endothelial growth factor receptor)

7
Q

Higher tumour grades associated with what mutation?

A

C-kit (esp MCTs)

8
Q

RTK treatments

A

–Toceranib phosphate (Palladia -Pfizer)
•Overall response in grade II tumors 42.8%
•Duration of response 12 weeks
–Masitinib (AB Science- Masivet or Kinavet)
•Better time to progression than placebo
•Not available in U.S. anymore

9
Q

Side effect of RTK treatments

A

–Significant GI and potential bone marrow suppression from both.

10
Q

Uses for RTKs

A

thyroid carcinoma, anal gland adenocarcinoma, maybe metastatic OSA

11
Q

importance of tumor blood vessels

A

–Delivery of nutrients, growth factors, hormones, oxygen
–Removal of wastes and toxins
–Immune surveliance

12
Q

Vascular disrupting

agents (VDAs) function how?

A

Preferentially destroy established tumor

blood vasculature

13
Q

Two methods of targeting tumor blood flow?

A

Vascular disrupting
agents (VDAs) and Supression of endothelial cell growth and
recruitment from bone marrow

14
Q

How to use agents that suppress endothelial growth?

A

– given continously

– Most useful when tumor burden is low

15
Q

two categories of drugs that target tumor vasculature

A

biologics and small molecules

16
Q

biologics as a drug that targets tumor vasculature

A

antibodies or peptides that deliver toxins and
procoagulant and pro-apoptotic effectors to tumor
endothelium
• VEGF often antigenic target (lots of others too)

17
Q

small molecules as a drug that targets tumor vasculature

A

agents that exploit known differences
between tumor and normal endothelium to induce severe
vascular dysfunction- often blocking receptors
• Thalidomide
• Toceranib

18
Q

strategies used in vetmed to block tumor angiogensis

A

– Toceranib
• Direct inhibitor of VEGF signaling
– Metronomic chemotherapy
• Low dose daily dosing of traditional drugs
• Theory- stop endothelial cells from multiplying in, and homing to
neoplastic tissues

19
Q

drugs used it meteronomic chemotherapy

A

Chlorambucil, cyclophosphamide, lomustine, satraplatin

20
Q

two pathways of apoptosis

A
• Intrinsic (mitochondrial)
– Affected by conventional therapies
– Mutations commonly occur rendering
tumors resistant to conventional
therapies
• Extrinsic (receptors)
– Novel therapies targeting here may
circumvent resistance
21
Q

Mechanism of immune tolerance by tumors

A

they are recognized as “self”

22
Q

3 mechanisms of mitigating immune tolerance by tumors

A
  • Active Nonspecific immune stimulation
  • Active Specific- Tumor vaccines
  • Passive- Antibody administration
23
Q

goals of tumor vaccines

A
  • Activate T-cells (↑ MHC on cell surface)

* Activate antigen presenting cellsvgfb0gtfr

24
Q

Why can targeting T cells be helpful in immune therapy

A
– Destroy immunosuppressive
environment around the tumor
– May use conventional drugs
• Metronomic chemo
• Cimetidine
25
Q

Why is gene therapy promising in treating cancer

A

– Correct the genetics of the tumor- e.g.inhibit
oncogenes, stimulate/replace tumor suppressor
genes
– Stimulate cytokine production
– Limitations- transduction efficiency

26
Q

how does PGE play a role in cancer development?

A
– Conversion of pro-carcinogens to
carcinogens
– Stimulation of tumor cell growth
– Prevention of apoptotic cell
death
– Promotion of angiogenesis
– Immune suppression