HGS-ETR1 had an effective pharmacokinetic half-life, and induced rapid tumour regression in multiple xenograft tumour models alone and in combination with chemotherapeutic agents.
This combination resulted in significant survival improvements in multiple murine tumour models, including breast and ovarian cancers, and was well tolerated.
Notably, we found that Uncl-Sema3E not only inhibited endothelial cells in culture, but its ectopic expression strongly impaired tumour angiogenesis and tumour growth in multiple preclinical tumour models in mice, either spontaneously or generated by cancer cell transplantation.
Compared to doxorubicin, SP1049C demonstrated superior antitumour activity in vivo in multiple animal tumour models and activity in doxorubicin-resistant settings (Batrakova et al, 1996; Alakhov et al, 1999).
It has also demonstrated antitumour effects in multiple tumour xenograft mouse models, including prostate, gastric, pancreatic, bladder, breast, gastric and hepatocellular cancers (Elices et al, 2005a; Greiner et al, 2007; LePage et al, 2007a; Guillen et al, 2009), as well as multiple myeloma (Ocio et al, 2009).
The putative therapeutic potential of Uncl-Sema3E was validated in multiple orthotopic or spontaneous tumour models in vivo, where either local or systemic delivery of Uncl-Sema3E-reduced angiogenesis, growth and metastasis, even in the case of tumours refractory to treatment with a soluble vascular endothelial growth factor trap.
However, associations between these risk factors and nodal status found in the standard polytomous logistic regression models were no longer significant in models considering multiple tumour characteristics simultaneously (Supplementary Tables 5 and 6 online).
Use of a novel extension of the polytomous logistic regression permitted simultaneous modelling of multiple tumour characteristics.
Several top candidates were converted to IgG1 and further characterised for agonist activity on multiple tumour cell types and antitumour activity in xenograft models.
Presented results importantly demonstrate that chaetocin has substantial activity in solid tumour models and not just in multiple myeloma as we had previously reported.
