Current and future approaches for the therapeutic targeting of metastasis (review).
Metastasis is the process whereby cancer cells disseminate and establish secondary tumors at distant sites from the primary tumor and is estimated to be responsible for approximately 90% of all cancer deaths. Cancers with metastatic spread are frequently resistant to conventional chemotherapeutic approaches, underlining the urgent need for novel treatments in these diseases. Recent advances in understanding the mechanisms underlining both the intrinsic cellular and extrinsic micro-environmental factors contributing to the metastatic process have resulted in the identification of a number of molecular targets for the development of specific anti-metastatic therapeutic strategies. These targets include intracellular enzymes such as the protein tyrosine kinases, cell surface receptors and their ligands, and elements of the extracellular matrix such as pro-angiogenic factors, protease enzymes and cytokines. Many of these pathways interact with each other, with the possibility of multiple downstream antineoplastic consequences as well as the potential for synergistic effects by targeting more than one of these factors. This review outlines several of the promising targets, and provides examples, of how these targets are being exploited as anti-metastatic therapies in conjunction with conventional treatments.
Germanov
Elitza
E
Department of Microbiology and Immunology, Faculty of Medicine, Dalhousie University, Sir Charles Tupper Medical Building, Nova Scotia B3H 1X5, Canada. germanov@dal.ca
Berman
Jason N
JN
Guernsey
Duane L
DL
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D018925:Chemokines / Q000627:therapeutic use; D006801:Humans; D020782:Matrix Metalloproteinases / Q000627:therapeutic use; D009362:Neoplasm Metastasis / Q000188:drug therapy*; D009369:Neoplasms / Q000473:pathology / Q000628:therapy*; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D018377:Neurotransmitter Agents / Q000627:therapeutic use; D011134:Polysaccharides / Q000627:therapeutic use; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects
D000970:Antineoplastic Agents; D018925:Chemokines; D018377:Neurotransmitter Agents; D011134:Polysaccharides; D047428:Protein Kinase Inhibitors; D043562:Receptors, G-Protein-Coupled; D011505:Protein-Tyrosine Kinases; D020782:Matrix Metalloproteinases