Antitumoral

Question 1

Toceranib (Palladia) is

Answer 1

tyrosine kinase inhibitor

Question 2

For what is toceranib used

Answer 2

to treat Patnaik grade II or III, recurrent, cutaneous mast cell tumors with or without regional lymph node involvement…

Question 3

Most common AE with toceranib

Answer 3

-diarrhoea
- loss of appetite, weight loss
-lameness,
- hematochezia
Nasal depigmentation

Question 4

Can toceranib be used in cats ?

Answer 4

yes

Question 4

What receptors does toceranib inhibit?

Answer 4

-RTK (receptor tyrosine kinase) called c-KIT
-VEGFR2 and PDGFR-beta

Question 5

MOA of toceranib

Answer 5

Tyrosine kinase inhibitors competitively inhibits ATP binding in target RTKs (receptors)
Blocks TK from transferring a phosphate group from ATP to proteins (ie prevents receptor phosphorylation)
Prevents downstream signal transduction and results in cell cycle arrest and tumour apoptosis

Question 6

The c-KIT gene (proto-oncogene) in mast cells encodes the c-KIT receptor (tyrosine kinase receptor) for _______ cell factor (SCF).

Answer 6

stem

Question 6

A gain of function mutation in the c-KIT gene results in constitutive ________ of the c-KIT receptor even in the absence of SCF binding.

Answer 6

activation

Question 7

The most common type of mutation is an internal tandem duplication (ITD) in exons 8 or ___ of the c-KIT gene.

Answer 7

11

Question 8

Mast cell tumours with c-KIT mutations tend to have a ________ prognosis and shorter survival time than those with wild-type c-KIT.

Answer 8

poorer

Question 9

Ki-67 and c-KIT are both immunohistochemical markers which help to determine the ______ in dogs with MCTs.

Answer 9

prognosis

Question 10

BRUTON’S TYROSINE KINASE=BTK

what is their function

Answer 10

-supports humoral activity
-critical in B cell development and function
-important in B cell receptor signalling and in cell migration

-BTK mediates B cell responses to antigen-engagement as well as stimulation via CD40, toll-like receptors, Fc receptors and chemokine receptors

-autoreactive B cells are more dependant upon BTK for survival than normal B cells
-there is 99% homology in BTK protein sequence alignment of all tested species- rodent, dog, nonhuman primate and human

Question 11

BRUTON’S TYROSINE KINASE INHIBITORS= BTKi

Answer 11

-inhibit BTK in non-T cell white blood cells (including B cells, neutrophils, and mast cells)
-reduce downstream signalling from the B cell receptor and FcgammaR (surface IgG receptor) on B and other non-T white blood cells
-they reduce ability of peripheral B cells to mature and interfere with cell proliferation, differentiation and survival
-effective in some B cell malignancies in dogs and humans