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Biology and therapeutic implications of VEGF‐A splice isoforms and single‐nucleotide polymorphisms in colorectal cancer
Author(s) -
Canavese Miriam,
Ngo Doan T.M.,
Maddern Guy J.,
Hardingham Jennifer E.,
Price Timothy J.,
Hauben Ehud
Publication year - 2017
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.30567
Subject(s) - angiogenesis , colorectal cancer , gene isoform , cancer research , metastasis , vascular endothelial growth factor , alternative splicing , biology , cancer , epigenetics , hif1a , medicine , oncology , gene , vegf receptors , genetics
Tumor growth, dissemination and metastasis are dependent on angiogenesis. The predominant vascular endothelial growth factor (VEGF) isoform that plays a major role in angiogenesis is VEGF‐A. Indeed, VEGF‐A is implicated in promoting angiogenesis of numerous solid malignancies, including colorectal cancer (CRC). A large body of preclinical and clinical evidence indicates that the expression of specific VEGF‐A isoforms represents a predominant pro‐angiogenic factor, which is associated with formation of metastases and poor prognosis in CRC patients. Different isoforms of human VEGF‐A have been identified, all of which arise from alternative splicing of the primary transcript of a single gene. Notably, it has been recently demonstrated that expression of type 3 isoform pattern is significantly correlated with venous involvement in CRC as well as in progression to metastatic colorectal cancer (mCRC), although it remains unclear what proportion of CRC tumors express these isoforms. This review highlights the importance of investigating the genetic and the epigenetic variations in VEGF‐A pathways in CRC, the functions of different VEGF‐A isoforms and their potential application as prognostic markers and/or therapeutic targets. Better understanding of the mechanisms controlling angiogenesis in liver metastases is necessary to address the limitations of current anti‐angiogenic therapies.