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Researchers detail possible resistance mechanisms of colorectal cancer to bevacizumab (Avastin)
Date:10/28/2013

A University of Colorado Cancer Center study published in the journal PLOS ONE shows that when colorectal cancer is targeted by the drug bevacizumab (Avastin), tumors may switch dependence from VEGF-A, which is targeted by the drug, to related growth factors in including VEGF-C, VEGF-D and placental growth factor. This change to new growth-factor dependence may allow colorectal cancer to push past bevacizumab's blockage of VEGF-A to continue to drive tumor growth.

"Think of it like damming a river. Bevacizumab can block the main flow, but then once a tumor's need builds up behind this dam, water starts to flow around the blockage in the form of streams and tributaries. That's like these other growth factors eventually a tumor becomes able to use these tributaries of VEGF-C, VEGF-D and placental growth factor to supply itself with the 'water' it needs," says Christopher Lieu, MD, investigator at the CU Cancer Center and assistant professor of Medical Oncology at the University of Colorado School of Medicine.

The analogy of liquid is an apt one bevacizumab slows cancer's growth by limiting a tumor's ability to grow the new blood vessels it needs to supply itself with nutrients. Especially in combination with chemotherapy, bevacizumab has proved an effective treatment for colorectal cancer. But then there frequently comes a point at which bevacizumab stops working and the tumor restarts its growth. This study asked why.

Specifically, Lieu and colleagues serially tested the levels of other VEGF-related growth factors in 42 patients treated with bevacizumab and chemotherapy, at many points during the course of their treatment.

"What we saw is that levels of VEGF-C and placental growth factor went up just before tumors progressed and then stayed high during the periods of tumor growth. Interestingly, VEGF-D was only elevated during progression. But it seems that tumors may be using these growth factors as ways to create bl
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Contact: Garth Sundem
garth.sundem@ucdenver.edu
University of Colorado Denver
Source:Eurekalert

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