These exploratory analyses suggest that in patients with mCRC addition of bevacizumab to IFL improves survival regardless of the level of VEGF or THBS-2 expression, or MVD.

We generated VEGF‐null fibrosarcomas from VEGF‐loxP mouse embryonic fibroblasts to investigate the mechanisms of tumor escape after VEGF inactivation. These cells were found to be tumorigenic and angiogenic in vivo in spite of the absence of tumor‐derived VEGF. However, VEGF derived from host stroma was readily detected in the tumor mass and treatment with a newly developed anti‐VEGF monoclonal antibody substantially inhibited tumor growth. The functional significance of stroma‐derived VEGF indicates that the recruitment of stromal cells is critical for the angiogenic and tumorigenic properties of these cells. Here we identified PDGF AA as the major stromal fibroblast chemotactic factor produced by tumor cells, and demonstrated that disrupting the paracrine PDGFR α signaling between tumor cells and stromal fibroblasts by soluble PDGFR α‐IgG significantly reduced tumor growth. Thus, PDGFR α signaling is required for the recruitment of VEGF‐producing stromal fibroblasts for tumor angiogenesis and growth. Our findings highlight a novel aspect of PDGFR α signaling in tumorigenesis.

The lungs are the second most common site of metastasis for colorectal cancer (CRC) after the liver. Rectal cancer is associated with a higher incidence of lung metastases compared to colon cancer. In China, the proportion of rectal cancer cases is around 50%, much higher than that in Western countries (nearly 30%). However, there is no available consensus or guideline focusing on CRC with lung metastases. We conducted an extensive discussion and reached a consensus of management for lung metastases in CRC based on current research reports and the experts’ clinical experiences and knowledge. This consensus provided detailed approaches of diagnosis and differential diagnosis and provided general guidelines for multidisciplinary therapy (MDT) of lung metastases. We also focused on recommendations of MDT management of synchronous lung metastases and initial metachronous lung metastases. This consensus might improve clinical practice of CRC with lung metastases in China and will encourage oncologists to conduct more clinical trials to obtain high-level evidences about managing lung metastases. Electronic supplementary material The online version of this article (10.1186/s13045-019-0702-0) contains supplementary material, which is available to authorized users.

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