G Aravantinos1, A Isaakidou1, T Karantanos2, A Sioziou3, G E Theodoropoulos2, D Pektasides4, M Gazouli3. 1. Third Department of Medical Oncology, General Oncology Hospital of Kifissia ``AgioiAnargyroi'', Athens, Greece. 2. First Department of Propaedeutic Surgery, School of Medicine, University of Athens, Athens, Greece. 3. Department of Basic Medical Sciences, Laboratory of Biology, School of Medicine, University of Athens, Athens, Greece. 4. Second Department of Internal Medicine, School of Medicine, University of Athens, Athens, Greece.
Abstract
BACKGROUND: Bevacizumab, an angiogenesis inhibitor is used in regimens for metastatic colorectal cancer (CRC). A minority of cancer cells with characteristics of cancer stem cells (CSC) may be responsible for progression and development of chemotherapy resistance in this disease. CD133 is a well-known CSC marker and is associated with angiogenesis, poor prognosis and resistance to chemotherapy. OBJECTIVE: The purpose of our study was to evaluate the association between the rs3130 and rs2286455 polymorphisms of the CD133 gene and the response, toxicity, and overall survival of patients with CRC on bevacizumab-based treatment. METHODS: Forty-three patients receiving bevacizumab, irinotecan and capecitabine and 15 patients receiving bevacizumab, irinotecan and 5-FU were included. Efficacy and toxicity were evaluated. KRAS mutation analysis and rs3130 and rs2286455 polymorphisms genotyping in the tumors and peripheral blood respectively were performed with PCR-RFLP. RESULTS: No association between KRAS mutated alleles and response was found. The rs3130 CC genotype was associated with reduced toxicity of treatments (p= 0.0017), and with lower overall survival on bevacizumab (p= 0.002). CONCLUSIONS: The CC genotype of rs3130 polymorphism in the CD133 gene can predict poorer overall survival in patients with metastatic CRC on bevacizumab which cannot be attributed to increased treatment toxicity.
BACKGROUND:Bevacizumab, an angiogenesis inhibitor is used in regimens for metastatic colorectal cancer (CRC). A minority of cancer cells with characteristics of cancer stem cells (CSC) may be responsible for progression and development of chemotherapy resistance in this disease. CD133 is a well-known CSC marker and is associated with angiogenesis, poor prognosis and resistance to chemotherapy. OBJECTIVE: The purpose of our study was to evaluate the association between the rs3130 and rs2286455 polymorphisms of the CD133 gene and the response, toxicity, and overall survival of patients with CRC on bevacizumab-based treatment. METHODS: Forty-three patients receiving bevacizumab, irinotecan and capecitabine and 15 patients receiving bevacizumab, irinotecan and 5-FU were included. Efficacy and toxicity were evaluated. KRAS mutation analysis and rs3130 and rs2286455 polymorphisms genotyping in the tumors and peripheral blood respectively were performed with PCR-RFLP. RESULTS: No association between KRAS mutated alleles and response was found. The rs3130 CC genotype was associated with reduced toxicity of treatments (p= 0.0017), and with lower overall survival on bevacizumab (p= 0.002). CONCLUSIONS: The CC genotype of rs3130 polymorphism in the CD133 gene can predict poorer overall survival in patients with metastatic CRC on bevacizumab which cannot be attributed to increased treatment toxicity.
Authors: Rafia S Al-Lamki; Jun Wang; Jun Yang; Natalie Burrows; Patrick H Maxwell; Timothy Eisen; Anne Y Warren; Sakari Vanharanta; Simon Pacey; Peter Vandenabeele; Jordan S Pober; John R Bradley Journal: Oncotarget Date: 2016-04-26
Authors: Xiaolan Pan; Lingsha Huang; Dan Mo; Yihua Liang; Zhaodong Huang; Bo Zhu; Min Fang Journal: Transl Cancer Res Date: 2020-10 Impact factor: 1.241