STAT3 inhibition with Galiellalactone effectively targets the prostate cancer stem-like cell population."

Cancer stem cells (CSCs) are a small subpopulation of quiescent cells with the potential to differentiate into tumor cells. CSCs are involved in tumor initiation and progression and contribute to treatment failure through their intrinsic resistance to chemo- or radiotherapy, thus representing a substantial concern for cancer treatment. Prostate CSCs’ activity has been shown to be regulated by the transcription factor Signal Transducer and Activator of Transcription 3 (STAT3). Here we investigated the effect of galiellalactone (GL), a direct STAT3 inhibitor, on CSCs derived from prostate cancer patients, on docetaxel-resistant spheres with stem cell characteristics, on CSCs obtained from the DU145 cell line in vitro and on DU145 tumors in vivo. We found that GL significantly reduced the viability of docetaxel-resistant and patient-derived spheres. Moreover, CSCs isolated from DU145 cells were sensitive to low concentrations of GL, and the treatment with GL suppressed their viability and their ability to form colonies and spheres. STAT3 inhibition down regulated transcriptional targets of STAT3 in these cells, indicating STAT3 activity in CSCs. Our results indicate that GL can target the prostate stem cell niche in patient-derived cells, in docetaxel-resistant spheres and in an in vitro model. We conclude that GL represents a promising therapeutic approach for prostate cancer patients, as it reduces the viability of prostate cancer-therapy-resistant cells in both CSCs and non-CSC populations

Cancer stem cells as a predictive factor in radiotherapy.

Cancer stem cell research is one of the most thriving and competitive areas in oncology research because it has the potential to dramatically affect clinical outcomes. Led by progress in hematology, cancer stem cell research has now provided evidence to play an important role for solid cancers as well. Because radiotherapy is only second to surgery in terms of its curative potency, it is very important for radiation oncologists to learn whether progress in cancer stem cell biology can enable them to exploit this knowledge to help cure more patients suffering from cancer. The present article gives an overview about the challenges of the cancer stem cell concept and highlights some important phenomena that are under intense investigation, such as phenotypic plasticity of stemness and impact and dynamics of microenvironmental niches. We discuss the potential and limitations of current experimental and theragnostic tools and end up with an agenda for future research as outlook for translational possibilities in the clinic