W6: Cancer Micorenvironment and Carcinogens

Question 1

How does hypoxia promote angiogenesis?

Answer 1

hypoxia increases HIF1a which drives expression of VEGF and bFGF

Question 2

What are components of tumor stroma (6)

Answer 2

ECM
fibroblast
blood vessels/lymphatics
adipose tissue
inflammatory cells
immune cells

Question 3

Full names:

HIF1a
VEGF
bFGF

Answer 3

HIF1a (hypoxia inducible factor 1a)
VEGF (vascular endothelial growth factor)
bFGF (basic fibroblast growth factor)

Question 4

a therapeutic target of angiogenesis in tumor

Answer 4

VEGF inhibitor

Question 5

in pancreatic ductal adenoma (PDA), the __ signaling pathway was targeted to decrease cancer stroma but failed because it acted on both cancer and normal cells

Answer 5

hedgehog

hedgehog inhibitor; it is now recommended to combine with other therapies

Question 6

oncogene __ is initiating event in pancreatic cancer

Answer 6

kras

Question 7

Cancer cells can direct killing of CTL (T killer cell) by generating apoptotic stimuli via __

Answer 7

FasL

Question 8

Cancer cell milieu can express factors that activate immune check points like

Answer 8

CTLA-4 and PD-L1

checkpoint proteins that block T cell activity

Question 9

Checkpoint with

CTLA-4:
PD-1:

Answer 9

CTLA-4: prevent DC and T cell interaction

PD-1: prevent T cell from attacking cancer cells

Question 10

For cancer therapy, these can turn on anergic or exhausted T cells (3)

Answer 10

anti CTLA-4
anti PD-1
anti PDL-1

Question 11

Cancer cell can promote immunosuppressive environment via promoting expansion of suppressor cells like

Answer 11

Treg

Question 12

immunosuppressive milieu of tumors (4)

Answer 12

FasL (kill CTL)

Treg (immune suppressor)

VEGF (inhibit mature DC ability to stimulate T cell)

Cytokines (promote T cell anergy)

Question 13

2 broad classes of carcinogens are __ and __; which one has to come before the other to induce cancer?

Answer 13

initiator, promoter

initiator has to come first