Cancer stem cells (CSCs) account for tumor initiation, invasiveness, metastasis, and recurrence in a broad range of human cancers. Although being a key player in cancer development and progression by stimulating proliferation and metastasis and preventing apoptosis, the role of the transcription factor NF-κB in cancer stem cells is still underestimated. In the present review, we will evaluate the role of NF-κB in CSCs of glioblastoma multiforme, ovarian cancer, multiple myeloma, lung cancer, colon cancer, prostate cancer, as well as cancer of the bone. Next to summarizing current knowledge regarding the presence and contribution of CSCs to the respective types of cancer, we will emphasize NF-κB-mediated signaling pathways directly involved in maintaining characteristics of cancer stem cells associated to tumor progression. Here, we will also focus on the status of NF-κB-activity predominantly in CSC populations and the tumor mass. Genetic alterations leading to NF-κB activity in glioblastoma, ependymoma, and multiple myeloma will be discussed.

Among the cell populations existing within a tumor, cancer stem cells are responsible for metastasis formation and chemotherapeutic resistance. In the present review, we focus on the transcription factor NF-κB, which is present in every cell type including cancer stem cells. NF-κB is involved in pro-tumor inflammation by its target gene interleukin 1 (IL1) and can be activated by a feed-forward loop in an IL1-dependent manner. Here, we summarize current strategies targeting NF-κB by chemicals and biologicals within an integrated cancer therapy. Specifically, we start with a tyrosine kinase inhibitor targeting epidermal growth factor (EGF)-receptor-mediated phosphorylation. Furthermore, we summarize current strategies of multiple myeloma treatment involving lenalidomide, bortezomib, and dexamethasone as potential NF-κB inhibitors. Finally, we discuss programmed death-ligand 1 (PD-L1) as an NF-κB target gene and its role in checkpoint therapy. We conclude, that NF-κB inhibition by specific inhibitors of IκB kinase was of no clinical use but inhibition of upstream and downstream targets with drugs or biologicals might be a fruitful way to treat cancer stem cells.

We retrospectively studied 73 consecutive patients who underwent surgery 2015–2020 for removal of cerebellar metastases (CM). Median overall survival (medOS) varied widely between patients and compared favorably with the more recent literature (9.2, 25–75% IQR: 3.2–21.7 months vs. 5–8 months). Prognostic factors included clinical (but not radiological) hydrocephalus (medOS 11.3 vs. 5.2 months, p = 0.0374). Of note, a third of the patients with a KPI 12 months. Chemotherapy played a prominent prognostic role (medOS 15.5 vs. 2.3, p < 0.0001) possibly reflecting advances in treating systemic vis-à-vis controlled CNS disease. Major neurological (≥30 days), surgical and medical complications (CTCAE III–V) were observed in 8.2%, 13.7%, and 9.6%, respectively. The occurrence of a major complication markedly reduced survival (10.7 vs. 2.5 months, p = 0.020). The presence of extracerebral metastases did not significantly influence OS. Postponing staging was not associated with more complications or shorter survival. Together these data argue for individualized decision making which includes offering surgery in selected cases with a presumably adverse prognosis and also occasional urgent operations in cases without a preoperative oncological work-up. Complication avoidance is of utmost importance.

For patients with HER2-overexpressing gastric cancer, there is an improved prognosis with additional trastuzumab to chemotherapy with a platinum compound and a fluoropyrimidin in first-line therapy. Second-line combinations are currently evaluated in various studies. We report the case of a 43-year-old male patient who came to our hospital with recurrent metastatic gastric cancer after curative surgery 18 months before. His disease responded well to several therapeutic regimens. Firstline chemotherapy with a combination of epirubicin, oxaliplatin and capecitabine (EOX) and the following therapies -- peritonectomy, multivisceral resection, hyperthermic intraperitoneal chemotherapy (HIPEC), and secondline chemotherapy with oxaliplatin, 5-fluorouracil and leucovorin (FLO) - induced a complete remission. At the time of the subsequent progression, HER2 overexpression was detected. We administered the combination of irinotecan, 5-fluorouracil, leucovorin (FOLFIRI) and trastuzumab, which to our knowledge was used for the first time in a patient with metastatic gastric cancer in third-line therapy. This regimen again induced a complete remission of the disease, which has been sustained now for at least 8 months. This is the first time in the literature that a combination of FOLFIRI and trastuzumab (FOLFIRIT) was used successfully in a patient with recurrent metastatic gastric cancer.

Zusammenfassung Hintergrund Patienten mit onkologischen Erkrankungen, insbesondere mit hämatologischen Neoplasien, haben ein erhöhtes Risiko für allgemeine Infektionen und spezielle therapieassoziierte Komplikationen mit hoher Morbidität und Mortalität. Die jährliche Inzidenz und Prävalenz für Krebserkrankungen steigt in Deutschland. Moderne Therapieverfahren haben zu einem verbesserten Überleben geführt, jedoch erfordern steigendes Alter, Komorbiditäten und Gebrechlichkeit der Patienten multidisziplinäre Strategien zur Durchführung komplexer Therapiekonzepte und zur Behandlung von deren Komplikationen. Methode Eine selektive Literaturrecherche sowie die Leitlinien der European Society for Medical Oncology (ESMO), der Deutschen Gesellschaft für Hämatologie und Medizinische Onkologie (DGHO), der Arbeitsgemeinschaft Infektionen in der Hämatologie und Onkologie der DGHO (AGIHO) und der American Society of Clinical Oncology (ASCO) sind die Grundlage für den vorliegenden Artikel. Schlussfolgerungen Das Erkennen schwerer Infektionen bei Krebspatienten und deren Unterscheidung von therapieassoziierten Komplikationen stellt eine Herausforderung für den behandelnden Arzt dar. Neutropenisches Fieber ist der häufigste infektiologische Notfall in der Onkologie. Frühzeitige empirische Therapie mit Breitspektrumantibiotika und eskalierende diagnostische Maßnahmen sind notwendig für die erfolgreiche Therapie dieser Risikogruppe. In diesem Beitrag wird eine Reihe von lebensbedrohlichen Infektionen bei immunkompromittierten Patienten diskutiert.