Mechanisms of tumour invasion and metastasis: emerging targets for therapy.
The progression of a tumour from one of benign and delimited growth to one that is invasive and metastatic is the major cause of poor clinical outcome in cancer patients. The invasion and metastasis of tumours is a highly complex and multistep process that requires a tumour cell to modulate its ability to adhere, degrade the surrounding extracellular matrix, migrate, proliferate at a secondary site and stimulate angiogenesis. Knowledge of the process has greatly increased and this has resulted in the identification of a number of molecules that are fundamental to the process. The involvement of these molecules has been shown to relate not only to the survival and proliferation of the tumour cell but, also to the processes of tumour cell adhesion, migration, and the tumour cells ability to degrade and escape the primary site as well as play a role in angiogenesis. These molecules may provide important therapeutic targets that represent the ability to target specific steps in the process of invasion and metastasis and provide additional therapies. The review focuses on representative key targets in each of these processes and summarises the state of play in each case.
Price
John T
JT
Bone Metastasis and Cell Migration Laboratory, St Vincent's Institute of Medical Research, Department of Surgery, University of Melbourne, St. Vincent's Hospital, Fitzroy, Melbourne, VIC 3065, Australia. jonp@ariel.its.unimelb.edu.au
Thompson
Erik W
EW
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D015820:Cadherins / Q000502:physiology; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D006801:Humans; D016023:Integrins / Q000037:antagonists & inhibitors / Q000502:physiology; D020782:Matrix Metalloproteinases / Q000378:metabolism; D009361:Neoplasm Invasiveness / Q000503:physiopathology*; D009362:Neoplasm Metastasis / Q000188:drug therapy* / Q000503:physiopathology; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000502:physiology; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051966:Phospholipase C gamma; D010960:Plasminogen Activators / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors / Q000502:physiology; D020741:rho GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000502:physiology
D000970:Antineoplastic Agents; D015820:Cadherins; D004791:Enzyme Inhibitors; D016326:Extracellular Matrix Proteins; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D016023:Integrins; D020782:Matrix Metalloproteinases; D009363:Neoplasm Proteins; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051966:Phospholipase C gamma; D010960:Plasminogen Activators; D011505:Protein-Tyrosine Kinases; D010738:Type C Phospholipases; D020741:rho GTP-Binding Proteins; C496050:PTK2 protein, human