title: Targeting therapy-resistant cancer stem cells by hyperthermia.
abstract: Eradication of all malignant cells is the ultimate but challenging goal of anti-cancer treatment; most traditional clinically-available approaches fail because there are cells in a tumour that either escape therapy or become therapy-resistant. A subpopulation of cancer cells, the cancer stem cells (CSCs), is considered to be of particular significance for tumour initiation, progression and metastasis. CSCs are considered in particular to be therapy-resistant and may drive disease recurrence, which positions CSCs in the focus of anti-cancer research, but successful CSC-targeting therapies are limited. Here, we argue that hyperthermia - a therapeutic approach based on local heating of a tumour - is potentially beneficial for targeting CSCs in solid tumours. First, hyperthermia has been described to target cells in hypoxic and nutrient-deprived tumour areas where CSCs reside and ionising radiation and chemotherapy are least effective. Second, hyperthermia can modify factors that are essential for tumour survival and growth, such as the microenvironment, immune responses, vascularisation and oxygen supply. Third, hyperthermia targets multiple DNA repair pathways, which are generally upregulated in CSCs and protect them from DNA-damaging agents. Addition of hyperthermia to the therapeutic armamentarium of oncologists may thus be a promising strategy to eliminate therapy-escaping and -resistant CSCs.
authors.affiliation: a Laboratory for Experimental Oncology and Radiobiology (LEXOR) , Center for Experimental and Molecular Medicine , Amsterdam , The Netherlands.|b Department of Radiotherapy , Academic Medical Center (AMC) and Cancer Center Amsterdam , Amsterdam , The Netherlands.
authors.forename: A L
authors.initials: AL
authors.lastname: Oei
authors.affiliation: c Department of Cell Biology and Histology , Academic Medical Center (AMC) and Cancer Center Amsterdam , Amsterdam , The Netherlands.
authors.forename: L E M
authors.initials: LEM
authors.lastname: Vriend
authors.affiliation: c Department of Cell Biology and Histology , Academic Medical Center (AMC) and Cancer Center Amsterdam , Amsterdam , The Netherlands.
authors.forename: P M
authors.initials: PM
authors.lastname: Krawczyk
authors.affiliation: d Department for Experimental Clinical Oncology , Aarhus University Hospital , Aarhus C , Denmark.
authors.forename: M R
authors.initials: MR
authors.lastname: Horsman
authors.affiliation: a Laboratory for Experimental Oncology and Radiobiology (LEXOR) , Center for Experimental and Molecular Medicine , Amsterdam , The Netherlands.|b Department of Radiotherapy , Academic Medical Center (AMC) and Cancer Center Amsterdam , Amsterdam , The Netherlands.
authors.forename: N A P
authors.initials: NAP
authors.lastname: Franken
authors.affiliation: b Department of Radiotherapy , Academic Medical Center (AMC) and Cancer Center Amsterdam , Amsterdam , The Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: Crezee
keywords: Hyperthermia; cancer stem cells; hypoxia; microenvironmental niche; radiation and chemotherapy resistance