Avtor/Urednik		Lah, Tamara T; Duran-Alonso, Maria Beatriz; van Noorden, Cornelis JF
Naslov		Antiprotease therapy in cancer: hot or not?
Tip		članek
Vir		Expert Opin Biol Ther
Vol. in št.		Letnik 6, št. 3
Leto izdaje		2006
Obseg		str. 257-79
Jezik		eng
Abstrakt		The activity of a set of peptidases (proteases) involved in cancer progression is collectively known as the cancer 'degradome'. Invasion and metastasis were initially considered as late events in cancer development and the processes in which proteases were involved. However, recent studies indicate that invasion and metastasis are not late events, but can occur during early stages as well. Moreover, other processes occurring in various stages of cancer progression are also protease-dependent, such as (upregulation of) cell proliferation, (downregulation of) apoptosis, involvement of white blood cells, angiogenesis and induction of multi-drug resistance. Proteolytic activity in tumours is regulated in a complex manner, as both genetically unstable cancer cells and stable stromal cells, such as fibroblasts, endothelial cells and inflammatory cells, are involved. In vitro studies and studies using animal models have clearly shown protease dependency of many processes in carcinogenesis. However, clinical trials using protease inhibitors have thus far been unsuccessful except for a few applications of matrix metalloprotease (MMP) inhibitors when used in combination with cytostatic anticancer agents and/or in the early stages of cancer. Antithrombotics, such as low-molecular-weight heparin and warfarin, were also successful in clinical trials, probably by interfering with proteases of the coagulation cascade. The two-way association between cancer and thrombosis has long been recognised in the clinic. The poor outcome of other clinical trials of protease inhibitors is probably due to the late stages of cancer of the patient populations included, and the limited understanding of the complex regulation and effects of the activity of the various proteases in tumours depending on, among others, tumour type and stage, interactions between the cancer cells, other cells and the extracellular matrix in tumours. Therefore, a better fundamen
Deskriptorji		NEOPLASMS NEOPLASM STAGING NEOPLASM INVASIVENESS NEOPLASM METASTASIS ASPARTIC PROTEINASES APOPTOSIS NEOVASCULARIZATION, PATHOLOGIC CYSTATINS CYSTEINE PROTEINASES GENE THERAPY LYSOSOMES METALLOPROTEINASES PLASMINOGEN ACTIVATOR INHIBITOR 1 SERINE PROTEINASES SURVIVAL ANALYSIS