Extracellular Targeting of Cell Signaling in Cancer: Strategies Directed at MET and RON Receptor Tyrosine Kinase Pathways

International experts present innovative therapeutic strategies to treat cancer patients and prevent disease progression

Extracellular Targeting of Cell Signaling in Cancer highlights innovative therapeutic strategies to treat cancer metastasis and prevent tumor progression. Currently, there are no drugs available to treat or prevent metastatic cancer other than non-selective, toxic chemotherapy. With contributions from an international panel of experts in the field, the book integrates diverse aspects of biochemistry, molecular biology, protein engineering, proteomics, cell biology, pharmacology, biophysics, structural biology, medicinal chemistry and drug development.

A large class of proteins called kinases are enzymes required by cancer cells to grow, proliferate, and survive apoptosis (death) by the immune system. Two important kinases are MET and RON which are receptor tyrosine kinases (RTKs) that initiate cell signaling pathways outside the cell surface in response to extracellular ligands (growth factors.) Both kinases are oncogenes which are required by cancer cells to migrate away from the primary tumor, invade surrounding tissue and metastasize. MET and RON reside on both cancer cells and the support cells surrounding the tumor, called the microenvironment. MET and RON are activated by their particular ligands, the growth factors HGF and MSP, respectively. Blocking MET and RON kinase activation and downstream signaling is a promising therapeutic strategy for preventing tumor progression and metastasis. Written for cancer physicians and biologists as well as drug discovery and development teams in both industry and academia, this is the first book of its kind which explores novel approaches to inhibit MET and RON kinases other than traditional small molecule kinase inhibitors. These new strategies target key tumorigenic processes on the outside of the cell, such as growth factor activation by proteases. These unique strategies have promising potential as an improved alternative to kinase inhibitors, chemotherapy, or radiation treatment.

Keywords: MET; c-MET, RON; HGFA; HGF, MSP, matriptase; hepsin; protease; peptidase; cancer; oncology; metastasis; KLK, SFTI-1; Serpin, PS-SCL; kinase; cell signaling; receptor tyrosine kinase; inhibitor; tumor microenvironment; antibody; growth factor; ligand; cytokine; chemotherapy; targeted therapy; peptidomimetic; therapeutic; Role of HGF/c-MET and MSP/RON driven pathways in Cancer; Cross-talk of c-MET and RON: Resistance mechanisms to Kinase Inhibitors; Hepatocyte Growth Factor Activator HGFA Discovery, function, and role in cancer; Matriptase Discovery, function, and role in cancer; Hepsin Discovery; Inhibitory antibodies of the proteases HGFA, matriptase, hepsin; Inhibitory antibodies of the growth factor HGF and kinase c-MET; Peptidomimetic and Small Molecule Inhibitors of HGFA, matriptase and Hepsin; Design of Cyclic Peptide serine protease inhibitors based on SFTI-1, Pharmaceutical & Medicinal Chemistry, Cell & Molecular Biology, Pharmaceutical & Medicinal Chemistry, Cell & Molecular Biology