Our results provide strong evidence that LOXmediated up-regulation of VEGF is responsible for the LOX dependent alterations in angiogenesis in vivo. Notably, immunohistochemical staining of a CRC TMA unveiled that LOX expression is clinically correlated with VEGF expression and blood-vessel development in patients, validating the results in vitro and in mouse models. Therapeutic Erlotinib clinical trial targeting of LOX may consequently supply a novel method to reduce VEGF mediated angiogenesis in CRC. Of note, one of the LOX household members, lysyl oxidase like 2, has been related to the regulation of sprouting angiogenesis within the zebrafish embryo. It will therefore be of great interest to help explore the role of the LOX members of the family in both fundamental and disease specific biological functions. In summary, our research has Cholangiocarcinoma demonstrated that LOX, an extracellular matrix modifying enzyme known to get a critical role in cancer development, promotes angiogenesis in in vitro and in vivo models of CRC. To get this we found that LOX was significantly related to blood-vessel density in patient samples. We’ve presented evidence of a novel link between LOX expression and VEGF secretion in vitro, in vivo and in patients, and shown this happens through PDGFRB mediated activation of Akt. Our results claim that inhibition of LOX in a therapeutic environment has potential to slow cancer development not just by suppressing invasion and metastasis, but in addition by reducing tumor angiogenesis. These results have crucial clinical implications for the development of novel strategies for treating cancer patients. The PI3K/Akt/mTOR path mediates multiple myeloma cell proliferation, survival, and growth of drug resistance, underscoring the role of mTOR inhibitors including rapamycin with potential anti MM task. But, recent data demonstrate a positive feedback loop from mTOR/S6K1 to Akt, whereby Akt activation natural product library confers resistance to mTOR inhibitors. We proved that elimination of mTOR signaling in MM cells by rapamycin was connected with upregulation of Akt phosphorylation. We hypothesized that curbing this positive feedback with a strong Akt chemical perifosine could complement rapamycin induced cytotoxicity in MM cells. Perifosine restricted rapamycin caused p Akt, causing increased cytotoxicity in MM. 1S cells also in the presence of IL 6, IGF 1 or bone marrow stromal cells. More over, rapamycin induced autophagy in MM. 1S MM cells as shown by electron microscopy and immunocytochemistry, was increased by perifosine. Mixture therapy improved apoptosis discovered by caspase/PARP cleavage and Annexin/PI analysis. Significantly, in vivo anti-tumor activity and prolongation of survival in a MM mouse xenograft type after treatment was increased with combination of perifosine and nabrapamycin. The caspases, and employing the in silico predictive evaluation we confirmed our experimental findings of this drug combination on PI3K, Akt, mTOR kinases.