Lenvatinib/VEGF

Question 1

What does Lenvatinib inhibit?

Answer 1

Lenvatinib mesilate (lenvatinib) selectively inhibits:

1) VEGFR1–3
2) proangiogenic and oncogenic pathway-related receptor tyrosine kinases (RTKs):
- FGFR1–4
- PDGFRα
- KIT
- RET

Question 2

How does lenvatinib impact immunosuppressive pathways?

Answer 2

lenvatinib may increase antitumor immunity through decrease of the TAM population by inhibiting the VEGFR and FGFR signaling pathways.

• The VEGFR signaling pathway also plays important roles in the migration of monocytes from bone marrow into tumors
• FGF2-mediated FGFR1 signaling pathway regulates the survival and migration of TAMs in the tumor microenvironment

Question 3

How does lenvatinib improve the efficacy of PD-1 inhibitors?

Answer 3

Upreguating type-I and type-II IFN signaling pathways
-The type-II IFN, IFN-γ, is a key cytokine in
the stimulation of a host antitumor immune response, including antigen presentation and T-cell trafficking
-Type-I IFN signal activation promotes the death of cancer cells and restricts tumor growth by altering the immune microenvironment
-Efficacy of PD-1 blockade is dependent on the activation status of the IFN pathway

Question 4

What are VEGF’s impact on the immune system?

Answer 4

VEGF

• mediate defects in DC function and maturation
• upregulates PD-L1 in myeloid DCs