Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2016 Nov 25;35(1):97.
doi: 10.1186/s40880-016-0162-7.

Implications of vessel co-option in sorafenib-resistant hepatocellular carcinoma

Elizabeth A Kuczynski  1 , Robert S Kerbel  2
Affiliations

Implications of vessel co-option in sorafenib-resistant hepatocellular carcinoma

Elizabeth A Kuczynski et al. Chin J Cancer. .

Abstract

The reason why tumors generally have a modest or transient response to antiangiogenic therapy is not well understood. This poses a major challenge for sorafenib treatment of advanced hepatocellular carcinoma (HCC) where alternate therapies are lacking. We recently published a paper entitled "Co-option of liver vessels and not sprouting angiogenesis drives acquired sorafenib resistance in hepatocellular carcinoma" in the Journal of the National Cancer Institute, providing a potential explanation for this limited benefit. We found that in mice bearing HCCs that had acquired resistance to sorafenib, tumors had switched from using angiogenesis for growth to co-opting the liver vasculature by becoming more invasive. Accumulating evidence suggests that many human tumor types may use vessel co-option, which has profound implications for the use of anti-angiogenic agents for cancer treatment.

Keywords: Hepatocellular carcinoma; Non-angiogenic; Resistance; Sorafenib; Vessel co-option.

PubMed Disclaimer

Figures

Fig. 1
Fig. 1
Proposed mechanism of acquired resistance to the multikinase inhibitor sorafenib in hepatocellular carcinoma (HCC). Highly angiogenic HCCs are initially responsive to sorafenib treatment. Over time, tumor cells become more invasive which promotes co-option of liver vessels in the face of angiogenesis blockade. EMT epithelial-to-mesenchymal transition
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Wilhelm SM, Adnane L, Newell P, Villanueva A, Llovet JM, Lynch M. Preclinical overview of sorafenib, a multikinase inhibitor that targets both Raf and VEGF and PDGF receptor tyrosine kinase signaling. Mol Cancer Ther. 2008;7(10):3129–3140. doi: 10.1158/1535-7163.MCT-08-0013. - DOI - PubMed
    1. Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008;359(4):378–390. doi: 10.1056/NEJMoa0708857. - DOI - PubMed
    1. Cheng AL, Kang YK, Chen Z, Tsao CJ, Qin S, Kim JS, et al. Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial. Lancet Oncol. 2009;10(1):25–34. doi: 10.1016/S1470-2045(08)70285-7. - DOI - PubMed
    1. Brizzi MP, Pignataro D, Tampellini M, Scagliotti GV, DiMaio M. Systemic treatment of hepatocellular carcinoma: why so many failures in the development of new drugs? Expert Rev Anticancer Ther. 2016;1:1–10. - PubMed
    1. Kuczynski EA, Yin M, Bar-Zion A, Lee CR, Butz H, Man S, et al. Co-option of liver vessels and not sprouting angiogenesis drives acquired sorafenib resistance in hepatocellular carcinoma. J Natl Cancer Inst. 2016;108(8):30. doi: 10.1093/jnci/djw030. - DOI - PMC - PubMed

MeSH terms