Week 4: Signal Transduction III: TKIs in Colon and CLL Flashcards Preview

IHO Ben > Week 4: Signal Transduction III: TKIs in Colon and CLL > Flashcards

Flashcards in Week 4: Signal Transduction III: TKIs in Colon and CLL Deck (17)
Loading flashcards...
1
Q

What can cause over expression?

A

DNA amplification, increased transcription, decreased degradation of mRNA or protein

2
Q

What usually causes constitutive activity?

A

Mutation in the gene

3
Q

What is the chemotherapy for colon cancer in metastatic setting? Does it cure anyone?

A

5-FU with either irinotecan or oxaliplatin; doesn’t clear unless it’s in the adjuvant setting, only extends life by 2 years in metastatic setting

4
Q

What gene is the driver of proliferation and survival in colon cancer?

A

EGFR

5
Q

What genes are constitutively active in the EGFR pathway?

A

Ras and Raf

6
Q

What is needed for the the blocking of EGFR to be successful?

A

Tumors that express wild-type ras and raf

7
Q

What is MOA of panitumumab?

A

blocks EGFR

8
Q

What can panitumumab be used to treat?

A

colon cancer, squamos cancers of head and neck, squamos cancers of cervix and penis

9
Q

What is the most common form of leukemia?

A

Chronic lymphocytic leukemia

10
Q

What are the two phenotypes of CLL?

A

node-predominant and leukemia (circuilating)

11
Q

What proteins are consider in the prognosis of CLL patients?

A

Ki67 and Bax/BCL-2 ratio

12
Q

What does CLL usually present with?

A

autoimmune phenomena: immune thrombocytopenic purpura, AIHA, autoimmune agranulocytosis. hypogammaglobulinemia and virulent infections

13
Q

What is constitutively expressed in CLL?

A

non-mutated Bruton’s tyrosine kinase

14
Q

What are the treatments for CLL?

A

Rituximab, chlorambucil, BTK inhibitors (Ibrutinib), Idelalisib, venetoclax (Bcl-2 modulator)

15
Q

What is the MOA of ibrutinib?

A

BTK inhibitor; covalent modifier of ATP binding site on BTK

16
Q

What is most common resistance to ibrutinib?

A

C481S, changing the nucleophilic -SH to a -OH. Others: PLC-gamma mutations

17
Q

What are strategies for eliminating growth promoting signals?

A

Lower blood hormone levels, block hormone receptor, block down-stream signaling between receptor and effector aparatus