To evaluate the efficacy and safety of oral fruquintinib, a vascular endothelial growth factor receptor (VEGFR) inhibitor, as third-line or later therapy in patients with metastatic CRC.
Expression of both HIF-2α and vascular endothelial growth factor (VEGFA, VEGFB, or VEGFC) was associated with a poor metastasis-free survival of CRC (HR = 6.95, HR = 113.51, and HR = 8.11, respectively).
We investigated the potential combination of VEGF inhibitors such as bevacizumab and its murine-counterpart; along with other anti-angiogenic agents and ONC201 in both CRC xenograft and patient-derived xenograft (PDX) models.
IHC analysis of TMAs further confirmed an inverse correlation between CD8A and VEGFA expression, and revealed a favorable OS for patients with CD8A<sup>Hi</sup>VEGFA<sup>Lo</sup> disease among right-side CRCs.
Anti-angiogenic therapies targeting vascular endothelial growth factor (VEGF) and its receptor (VEGF-R) are important treatments for a number of human malignancies, including colorectal cancers.
Our findings provide insight into the important role of SIRT2 in colon tumour angiogenesis and suggest that SIRT2/STAT3/VEGFA might be a novel prognostic biomarker and a potential therapeutic target for patients with colorectal cancer.
VEGF plays an important role in colorectal cancer (CRC) biology, and its inhibition by using bevacizumab, an anti-VEGF antibody, proved for the first time to be effective and became indispensable for the treatment of metastatic CRC (mCRC).
We used Luminex technology to investigate protein levels of the cytokines IL6, tumor necrosis factor-α (TNFα) and vascular endothelial growth factor (VEGF) to relate these to IL32 levels in CRC tissue.
Collectively, 4'-HW decreased the viability and reduced angiogenesis in CRC, which was associated with downregulation of VEGF-A expression by disrupting the PI3K/AKT pathway.
This resulted in the increased expression of matrix metalloproteinase 2 (MMP2), matrix metalloproteinase 9 (MMP9) and vascular endothelial growth factor (VEGF), and the subsequent promotion of CRC cell invasion.
The results showed that the expression of miR-34a was downregulated whereas TGF-β1 and VEGF were upregulated in CRC tumor tissues and peripheral blood macrophages.
The levels of VEGF and MMP-2 in portal vein serum of CRC patients can be used as effective indexes for judging the prognosis of CRC and predicting CLM.
It was observed that Tim-4 overexpression considerably enhanced CRC tumorigenesis in vivo and promoted angiogenesis through the upregulation of vascular endothelial growth factor (VEGF).
From a biological perspective, it has been demonstrated that HR2A could have a beneficial effect on CRC for many reasons: i) promotion of peri-tumoral lymphocyte growth and improvement of immune response against the tumor, ii) suppression of adhesion molecules which might favor metastasis, iii) anti-angiogenetic activity (reduction of VEGF), iv) increased production of some cytokines which may counteract tumor growth, such as tumor necrosis factor (TNF) alpha, interleukin (IL)-10 and IL-15.
Areas covered: This review aimed to summarize the actual body of knowledge available on the VEGF pathway in CRC, including currently available anti-angiogenic drugs and treatment challenges, mechanisms of resistance, promising predictive biomarkers and future perspectives.
The aim of the present study is to evaluate clock (cry1, cry2 and per2) and clock-controlled (vascular endothelial growth factor-a, early growth response protein 1 and estrogen receptor β) gene expression in colorectal cancer and adjacent tissue and identify a possible link between survival of patients and expression of above mentioned genes.
STAT3/STAT5 activation was observed in CRC-TANKs, and treatment with pimozide, a STAT5 inhibitor, reduced endothelial cell capability to form capillary-like networks, inhibiting VEGF and angiogenin production without affecting the levels of TIMP1, TIMP2, and MMP9, indicating that STAT5 is involved in cytokine modulation but not invasion-associated molecules.
These findings indicate that treatment with miR‑1 may be a novel method of tumor suppression, and provide a theoretical and experimental basis for the further targeted treatment of CRC through the regulation of miR‑1 and VEGF expression.
Furthermore, Angiotensin receptor inhibitors (ARIs) and angiotensin-converting enzyme Inhibitors (ACE-Is) demonstrate activity in CRC by their inhibition of both Insulin-like growth factor 1 (IGF-1) and Vascular endothelial growth factor (VEGF), and therefore present a potentially novel therapeutic strategy in colorectal cancer, which have summarized in the current review.