Targeting glioblastoma stem cells: The first step of photodynamic therapy.

Glioblastoma is one of the most malignant types of brain cancer. Evidence suggests that within gliomas there is a small subpopulation of cells with the capacity for self-renewal, called glioma stem cells. These cells could be responsible for tumorigenesis, chemo and radioresistance, and finally for the recurrence of the tumor. Fluorescence-guided resection have improved the results of treatment against this disease, prolonging the survival of patients by a few months. Also, clinical trials have reported potential improvements in the therapeutic response after photodynamic therapy. Thus far, there are few published works that show the response of glioblastoma stem-like cells to photodynamic therapy. Here, we present a brief review exclusively commenting on the therapeutic approaches to eliminate glioblastoma stem cells and on the research publications about this topic of glioblastoma stem cells in relation to photodynamic therapy. It is our hope that this review will be useful to provide an overview about what is known to date on the topic and to promote the generation of new ideas for the eradication of glioblastoma stem cells by photodynamic treatment.

Isolation and initial characterization of human glioblastoma cells resistant to photodynamic therapy.

Glioblastoma is the most severe form of brain cancer. Despite multimodal therapy combining surgery, radiotherapy and chemotherapy, prognosis of patients is dismal. It has been observed that the surgical resection guided by photosensitizer fluorescence followed by photodynamic therapy (PDT) prolongs the average survival in patients with glioblastoma. The main problem with all oncological treatments, including PDT, is the presence of resistant cells. The objective of this study was to isolate and perform an initial characterization of human glioblastoma cells resistant to PDT employing methyl-5-aminolevulinic acid. We obtained resistant cells from the T98 G cell line. Resistant populations accumulated less photosensitizer, formed spheroids of higher number of cells, had higher tumorigenic capacity, and expressed higher mRNA levels of fibroblastic growth factor receptor (FGFR), epidermal growth factor receptor (EGFR) and ß-platelet-derived growth factor receptor (ßPDGFR) than parental cells. The studies of glioblastoma resistance to PDT would help to better understand the causes of tumor recurrence after PDT and to develop new therapeutic proposals in this field of oncology.

Ecological photodynamic therapy: new trend to disrupt the intricate networks within tumor ecosystem.

As with natural ecosystems, species within the tumor microenvironment are connected by pairwise interactions (e.g. mutualism, predation) leading to a strong interdependence of different populations on each other. In this review we have identified the ecological roles played by each non-neoplastic population (macrophages, endothelial cells, fibroblasts) and other abiotic components (oxygen, extracellular matrix) directly involved with neoplastic development. A way to alter an ecosystem is to affect other species within the environment that are supporting the growth and survival of the species of interest, here the tumor cells; thus, some features of ecological systems could be exploited for cancer therapy. We propose a well-known antitumor therapy called photodynamic therapy (PDT) as a novel modulator of ecological interactions. We refer to this as "ecological photodynamic therapy." The main goal of this new strategy is the improvement of therapeutic efficiency through the disruption of ecological networks with the aim of destroying the tumor ecosystem. It is therefore necessary to identify those interactions from which tumor cells get benefit and those by which it is impaired, and then design multitargeted combined photodynamic regimes in order to orchestrate non-neoplastic populations against their neoplastic counterpart. Thus, conceiving the tumor as an ecological system opens avenues for novel approaches on treatment strategies.