Multifaceted targeting in cancer: the recent cell death players meet the usual oncogene suspects.
Recent complicated advances towards the blueprinting of the altered molecular networks that lie behind cancer development have paved the way for targeted therapy in cancer. This directed a significant part of the research community to the development of specialized targeted agents, many of which are already available or in clinical trials. The prospect of patient-tailored therapeutic strategies, although very close to becoming a reality also raises the level of complexity of the therapeutic approach. This review summarizes the functions, in vivo expression patterns and aberrations of factors presently targeted or representing potential targets by therapeutic agents, focusing on those implicated in death receptor-induced apoptosis. The authors overview the regulation of these factors and death receptor-induced apoptosis by classical oncogenes (e.g., RAS, MYC, HER2) and their effectors/regulators, most of which are also being targeted. In addition, the importance of orthologic systemic approaches in future patient-tailored therapies are discussed.
Drosopoulos
Konstantinos
K
Laboratory of Signal Mediated Gene Expression, Institute of Biological Research and Biotechnology, National Hellenic Research Foundation, Athens, Greece.
Pintzas
Alexander
A
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D002986:Clinical Trials as Topic; D016503:Drug Delivery Systems; D015195:Drug Design; D053222:Fas Ligand Protein / Q000502:physiology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D015513:Oncogene Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D009857:Oncogenes; D017434:Protein Structure, Tertiary; D053218:Receptors, Death Domain / Q000187:drug effects* / Q000235:genetics; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
D000970:Antineoplastic Agents; D053222:Fas Ligand Protein; D051034:Inhibitor of Apoptosis Proteins; D015513:Oncogene Proteins; D053218:Receptors, Death Domain; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D014409:Tumor Necrosis Factor-alpha