Molecular Targeting of Integrins and Integrin-Associated Signaling Networks in Radiation Oncology.
Radiation and chemotherapy are the main pillars of the current multimodal treatment concept for cancer patients. However, tumor recurrences and resistances still hamper treatment success regardless of advances in radiation beam application, particle radiotherapy, and optimized chemotherapeutics. To specifically intervene at key recurrence- and resistance-promoting molecular processes, the development of potent and specific molecular-targeted agents is demanded for an efficient, safe, and simultaneous integration into current standard of care regimens. Potential targets for such an approach are integrins conferring structural and biochemical communication between cells and their microenvironment. Integrin binding to extracellular matrix activates intracellular signaling for regulating essential cellular functions such as survival, proliferation, differentiation, adhesion, and cell motility. Tumor-associated characteristics such as invasion, metastasis, and radiochemoresistance also highly depend on integrin function. Owing to their dual functionality and their overexpression in the majority of human malignancies, integrins present ideal and accessible targets for cancer therapy. In the following chapter, the current knowledge on aspects of the tumor microenvironment, the molecular regulation of integrin-dependent radiochemoresistance and current approaches to integrin targeting are summarized.
OncoRay-National Center for Radiation Research in Oncology, Faculty of Medicine, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
Anne
A
Vehlow
OncoRay-National Center for Radiation Research in Oncology, Faculty of Medicine, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
Katja
K
Storch
OncoRay-National Center for Radiation Research in Oncology, Faculty of Medicine, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
Daniela
D
Matzke
OncoRay-National Center for Radiation Research in Oncology, Faculty of Medicine, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany. nils.cordes@oncoray.de.|Institute of Radiooncology, Helmholtz-Zentrum Dresden-Rossendorf, Dresden, Germany. nils.cordes@oncoray.de.
Nils
N
Cordes
D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D059248:Chemoradiotherapy; D006801:Humans; D016023:Integrins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008954:Models, Biological; D058990:Molecular Targeted Therapy / Q000379:methods*; D009369:Neoplasms / Q000378:metabolism / Q000628:therapy*; D018787:Radiation Oncology / Q000379:methods*; D015398:Signal Transduction / Q000187:drug effects* / Q000528:radiation effects*; D059016:Tumor Microenvironment / Q000187:drug effects / Q000528:radiation effects
D000911:Antibodies, Monoclonal; D016023:Integrins
Focal adhesion signaling; Integrins; Molecular targeting; Radiochemosensitization