Tedaviye yanıtsız kanser kök hücrelerinin hipertermi ile hedeflenmesi
Targeting therapy-resistant cancer stem cells by hyperthermia.
Int J Hyperthermia. 2017 Jan 19:1-23. doi: 10. 1080 / 02656736. 2017. 1279757. [Epub ahead of print]
Oei AL1,2, Vriend LE3, Krawczyk PM3, Horsman MR4, Franken NA1,2, Crezee J2.
Author information
• 1a Laboratory for Experimental Oncology and Radiobiology (LEXOR), Center for Experimental and Molecular Medicine, The Netherlands.
• 2b Department of Radiotherapy , The Netherlands.
• 3c Department of Cell Biology and Histology, Academic Medical Center (AMC) and Cancer Center Amsterdam, P.O. Box 22700, 1100 DE, Amsterdam, The Netherlands.
• 4d Department for Experimental Clinical Oncology, Aarhus University Hospital, 8000 Aarhus C, Denmark.
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 tumor 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 tumor 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 tumor - is potentially beneficial for targeting CSCs in solid tumors. First, hyperthermia has been described to target cells in hypoxic and nutrient-deprived tumor areas where CSCs reside and ionizing radiation and chemotherapy are least effective. Second, hyperthermia can modify factors that are essential for tumor survival and growth, such as the microenvironment, immune responses, vascularization 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.
KEYWORDS:
cancer stem cells; hyperthermia; hypoxia; microenvironmental niche; radiation and chemotherapy resistance
