Growth factors, cytokines and soluble forms of receptor molecules in cancer patients.
A wide range of growth factors has been identified in recent years, some of which have been found to play a crucial role in neoplastic processes. Some tumours produce considerable amounts of these peptides and their requirement for growth factors is often much reduced leading to a degree of autonomy which may itself contribute to tumourigenicity. In addition, growth factors such as TGF-alpha, PDGF, FGF and IGFs have been found to be overexpressed in tumours. The growth factor effector pathway is thus open to intervention, e.g. by blocking the receptor using specific antibodies or interfering with posttranscriptional activation. This is even more evident as oncogenes such as erbB and v-sis encode for growth factor receptors. Soluble receptors, due to high affinity binding, might also be used to sequester growth factors from its specific membrane-bound receptors. Tyrosine-specific protein kinase activity may be inhibited by tyrosine analogues such as erbstatin or by more specific tyrosine-kinase inhibitors. Some therapeutical concepts have already been developed in clinical trials. Tumour necrosis factor (TNF) has successfully been used in extremity melanoma and sarcoma and monoclonal antibodies directed against the EGF receptor has also been applied in patients with advanced squamous lung cancer. Synthetic growth factor analogues which bind to the receptor without eliciting a signal may soon become a supplementary part in cancer treatment. Growth factor action is also blocked by suramin and its analogues and clinical phase I and II trials are underway. These novel therapeutical aspects will profoundly change the nature of cancer treatment.
Zumkeller
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Department of Paediatric Oncology and Haematology, University Hospital Eppendorf, Hamburg, Germany.
Schofield
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PN
D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D017660:Autoreceptors / Q000037:antagonists & inhibitors / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D016207:Cytokines / Q000502:physiology* / Q000627:therapeutic use; D015195:Drug Design; D006131:Growth Inhibitors / Q000627:therapeutic use; D006133:Growth Substances / Q000502:physiology*; D006801:Humans; D009363:Neoplasm Proteins / Q000097:blood / Q000737:chemistry / Q000502:physiology*; D009369:Neoplasms / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology*; D015282:Octreotide / Q000627:therapeutic use; D017978:Receptors, Growth Factor / Q000737:chemistry / Q000187:drug effects / Q000502:physiology*; D012995:Solubility; D013498:Suramin / Q000627:therapeutic use
D000970:Antineoplastic Agents; D017660:Autoreceptors; D016207:Cytokines; D006131:Growth Inhibitors; D006133:Growth Substances; D009363:Neoplasm Proteins; D017978:Receptors, Growth Factor; D013498:Suramin; D015282:Octreotide