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One avenue towards the development of more selective anti-cancer drugs consists in the targeted delivery of bioactive molecules (drugs, cytokines, procoagulant factors, photosensitizers, radionuclides, etc.) to the tumor environment by means of binding molecules (e.g., human antibodies) specific to tumor-associated markers. In this context, the targeted delivery of therapeutic agents to newly-formed...
Tumour vascular disrupting agents (VDAs) are designed to target established tumour blood vessels, with the aim of permanently shutting down tumour blood flow, thereby inducing secondary tumour cell death. The microtubule-disrupting tubulin-binding agents are the largest sub-group of low molecular weight VDAs, a number of which are in advanced clinical development. In addition, a number of putative...
A growing body of preclinical and clinical evidence substantiates the feasibility of combining vascular disrupting agents (VDAs) and conventional anticancer therapies. The enhanced disease response to this combination is attributable to the respective activity of VDAs on the tumor vasculature and of the cytotoxic drug on proliferating tumor cells. However, the nature of the mode of action of VDAs...
Biomarkers are now an essential component of the process of drug development. Numerous biomarkers are being generated by a diverse range of disciplines but this chapter focuses specifically on the development of in vivo imaging biomarkers of tumour response to VDA therapy in preclinical models. In vivo imaging techniques are particularly attractive to monitor VDA therapies as they (1) are non-invasive,...
A highly reproducible characteristic of vascular disrupting agent (VDA)-mediated anti-tumor therapy is the retention of a rim of viable tumor tissue surrounding a much larger central mass of necrotic tissue within days of therapy. Repopulation from the viable rim subsequently compromises much of the striking initial anti-tumor effect frequently caused by the VDA treatment. The repopulation process...
A number of clinically applicable imaging techniques are able to assess the antivascular effects of antiangiogenic drugs and vascular disruptive agents (VDAs) via changes induced in functional kinetic parameters. These techniques include dynamic contrast enhanced magnetic resonance imaging (DCE-MRI), dynamic susceptibility enhanced MRI, diffusion MRI, positron emission tomography (PET) with oxygen...
New strategies to detect tumor angiogenesis and monitor response of tumor vasculature to therapy are needed. There are a plethora of anti-angiogenic strategies being evaluated pre-clinically and in the clinical setting; however, a significant unmet challenge is following the response of tumors to anti-angiogenic therapy. Herein we review current modalities being investigated for this purpose and...
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