The role of pericytes on the efficacy of bevacizumab in colorectal cancer.

BACKGROUND: Pericytes are mesenchymal cells surrounding capillary vessels and are known to play an essential role in tumor angiogenesis. Chondroitin sulfate proteoglycan 4 (CSPG4) is a cell surface proteoglycan and its release from pericytes and vascular smooth muscle cells is very important in tumor angiogenesis. Bevacizumab, which is a monoclonal antibody frequently used in the treatment of metastatic colorectal cancer, binds to the ligand of vascular endothelial growth factor A (VEGFA) and inhibits tumor angiogenesis. However, no reliable biomarker for predicting patients that will show a good response to this therapy has been established yet. In this study, we aimed to identify the significance of the presence of pericyte and VEGFA and CSPG4 expressions on the efficacy of Bevacizumab. METHODS: Fifty patients with metastatic or recurrent colorectal cancer who had been treated with Bevacizumab combined chemotherapy treatment were included in the study. The expressions of VEGFA and CSPG4 genes and also human ß-actin as the reference gene were examined using the quantitative real-time polymerase chain reaction method in the formalin-fixed paraffinembedded tumor tissues. For determining vascular and pericyte density in tumor tissue, immunohistochemical analysis was performed with CD31, alpha-smooth muscle actin, and CD34 antibodies. RESULTS: CSPG4 positive group had better objective response rate, as well as longer progression-free and overall survival than CSPG4 negative ones. Progression-free survival was significantly longer in VEGFA low group and CD31 low group. No significant correlation was found between CD34 positivity, SMA positivity, and progression-free and overall survival. DISCUSSION: Our results suggested that bevacizumab may be more effective in patients having less vascular density in the tumor tissue. But further studies are needed to support this finding.

Recent Advances in Cancer Stem Cell Targeted Therapy.

The cancer stem cells (CSCs) are a subpopulation of cancer cells with unique properties of self-renewal and differentiation potential. Recent evidence suggests that these cells might be responsible for tumor relapse and treatment resistance. Conventional cancer treatment modalities like chemotherapy and radiotherapy usually fail in eradicating CSCs in a tumor mass. Preclinical studies aiming at targeting CSCs have yielded great promise to increase the cancer cure rate. Likewise, targeting of conventional chemotherapeutic drugs to the CSCs and new small molecule inhibitors of stem-cell signaling pathways in humans carry the potential of improving the cancer management. Dendritic cell (DC)-based vaccines seem to be safe and efficient tools in targeting CSCs. The combination of DC vaccines with immune-checkpoint inhibitors is also promising. The viral vectors, particularly the oncolytic viruses, targeting CSCs have emerged as potential curative agents in cancer treatment. Here, we review the recent advances in targeting CSCs via stem cell markers, signaling pathways, immune system, cancer vaccines, and viral treatments.