The use of tyrosine kinase inhibitors in modifying the response of tumor microvasculature to radiotherapy.

Abstract:

:The response of the tumor microvasculature to ionizing radiation can be modified to improve tumor control in preclinical mouse models of cancer. Recent studies have shown that a variety of cancer drugs can improve the response of cancers to radiotherapy. Protein tyrosine kinase inhibitors (TKIs) have been shown to enhance radiation-induced destruction of tumor blood vessels. Among these compounds are inhibitors of a broad spectrum of receptor tyrosine kinases (RTKs). Inhibition of RTKs attenuates downstream signaling from various angiogenic growth factors, including vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), and fibroblast growth factor (FGF). RTK inhibitors with various specificities against the receptors for VEGF, PDGF, and FGF manifest significant antiangiogenic activities as well. We have shown using tumor vascular window model and tumor growth delay assays that these compounds can enhance tumor radiation response by attacking tumor microvasculature. Furthermore, we have shown that radiation and RTK inhibitors exert their antiangiogenic effect through inhibition of the PI3K/Akt signaling pathway, which results in induction of apoptosis. Our studies have provided a basis for future clinical investigations of combining radiotherapy and RTK inhibitors.

authors

Lu B,Shinohara ET,Edwards E,Geng L,Tan J,Hallahan DE

doi

10.1177/153303460500400614

keywords:

subject

Has Abstract

pub_date

2005-12-01 00:00:00

pages

691-8

issue

6

eissn

1533-0346

issn

1533-0338

pii

d=3022&c=4191&p=13211&do=detail

journal_volume

4

pub_type

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