Cancer

Patient sample, cell culture and mouse studies suggest inhibiting ARPC3 in combination with angiogenesis inhibitors could help treat metastatic colorectal cancer. In patients treated with Avastin bevacizumab, high levels of ARPC3 in liver metastases were associated with high tumor co-option of sinusoidal vessels - a non-angiogenic vascularization process - and poor survival. Also in liver metastases from patients, levels of sinusoidal vessel co-option were higher in metastases that developed during Avastin treatment than in untreated metastases and those that developed before treatment. In a human colorectal cancer cell line, shRNA targeting ARPC3 decreased migration compared with scrambled shRNA. In a xenograft mouse model of metastatic colorectal cancer, shRNA targeting ARPC3 combined with Xeloda capecitabine and an anti-VEGF-A mAb decreased metastatic liver tumor growth and blood vessel density in liver metastases compared with the shRNA alone or Xeloda plus the anti-VEGF-A mAb. Next steps could include identifying and testing ARPC3 inhibitors in combination with angiogenesis inhibitors.

Roche, its Genentech Inc. unit, and Chugai Pharmaceutical Co. Ltd. market Avastin, a humanized mAb against vascular endothelial growth factor (VEGF), to treat colorectal and other cancers...