title: Targeting the heat shock response in combination with radiotherapy: Sensitizing cancer cells to irradiation-induced cell death and heating up their immunogenicity.
abstract: Radiotherapy represents an essential treatment option for the majority of cancer patients in different stages of their disease. Physical achievements of the recent years led to the implementation of high precision treatment planning procedures, and image-guided dose delivery is current state of the art. Yet, radiotherapy still faces several limitations with cancer intrinsic radioresistance being a key driver of therapeutic failure. Accordingly, the mechanisms orchestrating radioresistance and their therapeutic targeting by combined modality approaches are in the center of attention of numerous radiation oncologists. In the present review, we summarize and discuss therapeutic approaches that exploit the heat shock response, either by hyperthermia or by pharmacological heat shock protein inhibition, in combination with radiotherapy. These strategies appear particularly promising, since they sensitize cancer cells to irradiation-induced cell death and at the same time have proven the potential to promote systemic anti-tumor immune mechanisms, which may target not only locally surviving tumor cells, but also distant out-of-field metastases.
authors.affiliation: Clinic for Radiotherapy and Radiation Oncology, Ludwig-Maximilians-University Munich, Germany. Electronic address: kirsten.lauber@med.uni-muenchen.de.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Lauber
authors.affiliation: Clinic for Radiotherapy and Radiation Oncology, Ludwig-Maximilians-University Munich, Germany.
authors.forename: Nikko
authors.initials: N
authors.lastname: Brix
authors.affiliation: Clinic for Radiotherapy and Radiation Oncology, Ludwig-Maximilians-University Munich, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Ernst
authors.affiliation: Clinic for Radiotherapy and Radiation Oncology, Ludwig-Maximilians-University Munich, Germany.
authors.forename: Roman
authors.initials: R
authors.lastname: Hennel
authors.affiliation: Clinic for Radiotherapy and Radiation Oncology, Ludwig-Maximilians-University Munich, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Krombach
authors.affiliation: Clinic for Radiotherapy and Radiation Oncology, Ludwig-Maximilians-University Munich, Germany.
authors.forename: Heike
authors.initials: H
authors.lastname: Anders
authors.affiliation: Clinic for Radiotherapy and Radiation Oncology, Ludwig-Maximilians-University Munich, Germany.
authors.forename: Claus
authors.initials: C
authors.lastname: Belka
mesh_terms: D000818:Animals; D016923:Cell Death / Q000276:immunology / Q000528:radiation effects; D003131:Combined Modality Therapy; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors* / Q000276:immunology; D006360:Heat-Shock Proteins / Q000276:immunology; D018869:Heat-Shock Response / Q000276:immunology / Q000528:radiation effects*; D006801:Humans; D006979:Hyperthermia, Induced / Q000379:methods*; D009369:Neoplasms / Q000276:immunology* / Q000532:radiotherapy*
chemical_list: D018841:HSP90 Heat-Shock Proteins; D006360:Heat-Shock Proteins
keywords: Heat shock protein; Heat shock response; Hyperthermia; Immunotherapy; Radiotherapy