Inhibition of the Soluble Extracellular Domain of E-cadherin: A Novel Tumoricidal drug for Cancers

Using biological or small molecule drugs to sequester or inhibit tumor-derived sEcad in the tumor cell microenvironment

One of the greatest challenges encountered in the development of novel anticancer therapies is the inability of the therapeutic agents to distinguish between normal healthy tissues and aberrant cancerous cells. The non-selective cytotoxicity andnarrow therapeutic index of these chemotherapeutic agents results in an untoward systemic drug toxicity that is debilitating to patients and heightens overall patient mortality. Thus, an important attribute of promising new anticancer drugs is todevelop an agent that has the ability to selectively target cancer cells, while sparing deleterious effects on normal healthy cells and tissues.

Dr. Sabine Brouxhon, MD at Stony Brook University proposes the use of biological or small molecule drugs to sequester or inhibit tumor-derived sEcad in the tumor cell microenvironment. These strategies would include, but not be limited to, usingmonoclonal antibodies, mini-antibodies, recombinant antibody constructs, antibody-drug conjugates, and gene therapy of the extracellular fragment of sEcad. In addition, encapsulation of this anti-sEcad Ab with microparticulate formulations ornanoparticulate carriers can be utilized in order to achieve the stability and modified-release required for a sustained cytolytic delivery system to tumor-derived tissue sites.

Optimize drug dosing and scheduling. Rapidly distinguish responders from nonresponders to this therapeutic invention. Continuous monitoring of a patients tumor response to therapy.

Prevention and/or treatment of squamous cell cancers of the skin or melanomas

PCT Publication No. WO 2012-058418

Animal and in-vitro data is available. Antibodies need to be humanized.

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Soluble E-cadherin, breast cancer, skin cancer, lung cancer, necrosis, apoptosis, cell death, p53, tumoricidal drug

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