Background The aim of the present retrospective study was to analyze medical outcome and risk factors associated with treatment outcomes according to KRAS status in patient with metastatic colorectal malignancy (mCRC) treated with bevacizumab (bev) plus chemotherapy in the first-line setting. median PFS in individuals with wild-type KRAS (wtKRAS) vs mutant KRAS was 11.5 vs 11.4 months respectively. The median OS was 30.7 vs 28.4 months (p = 0.312). Individuals with KRAS mutation experienced lung metastases more frequently than wtKRAS individuals (32.0% vs 23.8%; p = 0.001). We observed no difference in medical end result PR65A between hepatic and extrahepatic metastatic disease. Summary KRAS mutation does not interfere with medical benefit from first-line treatment with bevacizumab plus chemotherapy in mCRC individuals. Electronic supplementary material The online version of this article (doi:10.1186/s12876-015-0266-6) contains supplementary material which is available to authorized users. [6] and more Bardoxolone (CDDO) aggressive biological behavior [7]. Additionally Ras signaling advertised angiogenesis through repression of anti-angiogenic thrombospondin-1 [8]. Therefore Ras oncogenes may contribute to tumor progression by both a direct effect on tumor cell proliferation as well as indirectly by facilitating tumor angiogenesis inside a Bardoxolone (CDDO) paracrine fashionexperiments showing that KRAS mutation is definitely Bardoxolone (CDDO) a predictor of oxaliplatin level of sensitivity in colon cancer cells it has been suggested that mutant KRAS CRC individuals might benefit more from receiving first-line oxaliplatin-based regimens [17]. Although we have not observed a better response in KRAS mutated mCRC individuals treated with bev/OX-based therapy over those with wtKRAS as it was reported when individuals with advanced CRC were treated in the 1st collection with FOLFOX-6 [18] the reported level of sensitivity of mutated KRAS carcinoma cells to oxaliplatin may clarify the improved medical end result when KRAS mutant individuals were treated with bev/OX-based over bev/IRI-based therapy. We have confirmed that individuals showing with synchronous metastases have an inferior prognosis compared to individuals with metachronous metastases. Among the evaluated guidelines metastatic involvement of multiple organs at time of treatment initiation was the strongest prognostic element reducing both PFS and OS. Within the subgroup of individuals with metastatic disease limited to one distant organ we did not observed difference in Bardoxolone (CDDO) medical outcome with regard to hepatic or extrahepatic (including pulmonary) involvement. Interestingly together with Rossi [19] we notice trend toward longer both PFS and OS in individuals with extrahepatic disease and KRAS mutation than in wtKRAS subgroup when treated with bevacizumab plus chemotherapy. Apart from this truth we while others [20-22] have reported that KRAS mutation in colorectal malignancy itself is associated with pulmonary metastasis. Findings from your VICTOR trial showing that KRAS mutant tumors are associated with an increased risk of lung relapse in CRC individuals supported the part of chest imaging in monitoring Bardoxolone (CDDO) of colorectal malignancy Bardoxolone (CDDO) individuals particularly of those with resected main mutated KRAS carcinoma [20 22 The reason behind improved incidence of lung metastases in KRAS mutated colorectal tumors remains unknown at this moment. Considering the decreased proportion of lymph node metastasis in mutated KRAS individuals compared to wtKRAS subgroup (Table?1 [23 24 it seems that carcinoma cells with activating mutation in KRAS may exhibit a more hematogenous metastatic spread rather than along a lymphogenous path. Survival of tumor cells within the bloodstream and adhesion in the vasculature in the metastatic sites depend on tumor cell – platelet relationships [25]. We hypothesize that activating mutation of KRAS inducing manifestation of molecules responsible for connection with platelets such as tissue element [26] cyclooxygenase and metalloproteinase-9 [27] or cathepsin B [28] might contribute to improved protection of these carcinoma cells against shear stress as well as to enhanced adhesion properties which in turn prospects to onset of pulmonary metastasis of mutated KRAS carcinoma cells and higher metastatic activity in general [29]. The present study is definitely a retrospective analysis and thus an unintentional selection bias for any subset of individuals is possible. However the guidelines of our analysis that confer considerable reliability to the presented results are for example unselective multicenter input of evaluated.