Cancer and Precision Medicine

Question 1

Retinoblastoma

Answer 1

AD transmission
RB1 gene on chr 13 (first tumor suppressor gene discovered)
90% penetrance
most common eye tumor in children

Question 2

CML

Answer 2

driven by single chromosomal translocation- bcr-abl
imatinib therapy- high response rate
or other tyrosine kinase inhibitor

Question 3

How do cancer avoid lysis by immune cells

Answer 3

membrane bound inhibitory immune checkpt ligands- PD-L1 and PD-L2
soluble immnosuppressive factors- IL-10, TGF-B, PGE2
Downregulation of MHCI to mutated antigen can’t be presented

Question 4

Inhibitory T cell checkpts

Answer 4

Normal resolution of immune response
induce peripheral tolerance

PD-1, CTLA-4 (competes with CD-28 which is an activating molecule)
CTLA4 (ipilimumab) inhibitors function during antigen presentation
PD-1 inhibitors (nivolumab) function at T cell/tumor cell interface