Preoperative S-1 Therapy for Squamous Cell Carcinoma of The Head and Neck During the Waiting Period Before Surgery

Background: In patients with squamous cell carcinoma of head and neck (SCCHN), delayed surgery can result in poorer postoperative function and prognosis due to the growth of the tumor and the extended surgery. Further, delay may even make the tumor unresectable. To prevent tumor growth during the waiting period before surgery, S-1 has been administrated preoperatively at several facilities in Japan. To date, however, the safety and efficacy of preoperative S-1 remains unclear.Methods: We conducted a retrospective cohort study of 118 patients with SCCHN treated with S-1 before radical surgery at 2 institutions in Japan. We evaluated the safety of S-1 therapy, which was evaluated by the incidence of grade 3 or greater adverse events (AEs). The rate of achievement of the non-growth of tumors was also calculated.Results: Regarding safety, 125 AEs of all grades were recorded in 71 patients (60%). Of these, grade 3 AEs were detected in 3 patients (3%), and no grade 4 or 5 AEs occurred. The non-growth rate of primary lesions and lymph node metastases was 89% and 85%, respectively. Conclusion: Our data showed that preoperative S-1 therapy might be useful with acceptable toxicity on an outpatient basis in patients with SCCHN.

Anticancer Effects of Seaweed-Derived Bioactive Compounds

Cancer remains a major life-threatening disease worldwide. The development of anticancer drugs using natural products obtained from marine organisms has been proposed as an alternative approach. Seaweeds are the mainstay of marine ecosystems; therefore, they are highly enriched with diverse bioactive compounds. In the past decade, a vast number of natural compounds, such as polysaccharides, polyphenols, carotenoids, and terpenoids, have been isolated from seaweeds. Seaweeds have bioactive compounds that show cytotoxicity in various cancer cell lines. These compounds prevent tumor growth by inducing apoptotic cell death and arrest growth by interfering with different kinases and cell cycle pathways. This review discussed the anticancer properties of various bioactive compounds isolated from different types of seaweeds and their therapeutic potential against cancers.

Emerging Role of E2F Family in Cancer Stem Cells

The E2F family of transcription factors (E2Fs) consist of eight genes in mammals. These genes encode ten proteins that are usually classified as transcriptional activators or transcriptional repressors. E2Fs are important for many cellular processes, from their canonical role in cell cycle regulation to other roles in angiogenesis, the DNA damage response and apoptosis. A growing body of evidence demonstrates that cancer stem cells (CSCs) are key players in tumor development, metastasis, drug resistance and recurrence. This review focuses on the role of E2Fs in CSCs and notes that many signals can regulate the activities of E2Fs, which in turn can transcriptionally regulate many different targets to contribute to various biological characteristics of CSCs, such as proliferation, self-renewal, metastasis, and drug resistance. Therefore, E2Fs may be promising biomarkers and therapeutic targets associated with CSCs pathologies. Finally, exploring therapeutic strategies for E2Fs may result in disruption of CSCs, which may prevent tumor growth, metastasis, and drug resistance.

A Functional GM-CSF Receptor on Dendritic Cells Is Required for Efficient Protective Anti-Tumor Immunity

Dendritic cells (DC) play a major role during the priming phase of anti-tumor immunization, as they are required for an efficient tumor-associated antigens presentation. At least one dendritic cell-based therapy has already been successfully approved by regulators for clinical application in prostate cancer patients. Moreover, DC development is dependent on the granulocyte macrophage colony stimulating factor (GM-CSF), a cytokine that has been successfully used as a potent inducer of anti-tumoral immunity. To better understand the relation between DC and GM-CSF in anti-tumor immunity, we studied the DC function in mice lacking the cytokine receptor common subunit beta (βc-/-) for GM-CSF, IL-3 and IL-5 and immunized with irradiated tumor cells. Such immunization induces a protective, specific tumor immunization in wild-type mice, while βc-/- mice failed to mount an immune response. Upon in vitro stimulation, DC from βc-/- mice (DCβc-/-) are unable to undergo a full maturation level. In vivo experiments show that they lack the ability to prevent tumor growth, in contrast to DCWT. Moreover, matured DCWT rescued immunization in βc-/- mice. DC maturation is dependent on a functional pathway involving GM-CSF signaling through a biologically functional receptor. These findings may contribute to new strategies for efficient anti-tumor immunotherapies.

Anticancer Mechanisms of Salinomycin in Breast Cancer and Its Clinical Applications

Breast cancer (BC) is the most frequent cancer among women worldwide and is the leading cause of cancer-related deaths in women. Cancer cells with stem cell-like features and tumor-initiating potential contribute to drug resistance, tumor recurrence, and metastasis. To achieve better clinical outcomes, it is crucial to eradicate both bulk BC cells and breast cancer stem cells (BCSCs). Salinomycin, a monocarboxylic polyether antibiotic isolated from Streptomyces albus, can precisely kill cancer stem cells (CSCs), particularly BCSCs, by various mechanisms, including apoptosis, autophagy, and necrosis. There is increasing evidence that salinomycin can inhibit cell proliferation, invasion, and migration in BC and reverse the immune-inhibitory microenvironment to prevent tumor growth and metastasis. Therefore, salinomycin is a promising therapeutic drug for BC. In this review, we summarize established mechanisms by which salinomycin protects against BC and discuss its future clinical applications.

Revisiting CCL-type chemokines in breast cancer and its milieu: Prominent targetable chemokines, CCL8 and CCL21.

The patterns of chemokine expression play a decisive role in both breast cancer prognosis and metastasis. In a recent article published in Bioscience Reports 2020, “Bioinformatics identification of CCL8/21 as potential prognostic biomarkers in breast cancer microenvironment”, Chen et al. presented that expression of both CCL8 and CCL21 among CCL-type chemokines is prominent for prognosis of the breast cancer, metastasis and chemoresistance. Identifying the sources of the CCL8 and CCL21 in the tumor microenvironment and developing targeting strategies for these chemokines to prevent tumor growth will improve both prognosis and therapeutic outcomes.

Integrase-Defective Lentiviral Vector Is an Efficient Vaccine Platform for Cancer Immunotherapy

Integrase-defective lentiviral vectors (IDLVs) have been used as a safe and efficient delivery system in several immunization protocols in murine and non-human primate preclinical models as well as in recent clinical trials. In this work, we validated in preclinical murine models our vaccine platform based on IDLVs as delivery system for cancer immunotherapy. To evaluate the anti-tumor activity of our vaccine strategy we generated IDLV delivering ovalbumin (OVA) as a non-self-model antigen and TRP2 as a self-tumor associated antigen (TAA) of melanoma. Results demonstrated the ability of IDLVs to eradicate and/or controlling tumor growth after a single immunization in preventive and therapeutic approaches, using lymphoma and melanoma expressing OVA. Importantly, LV-TRP2 but not IDLV-TRP2 was able to break tolerance efficiently and prevent tumor growth of B16F10 melanoma cells. In order to improve the IDLV efficacy, the human homologue of murine TRP2 was used, showing the ability to break tolerance and control the tumor growth. These results validate the use of IDLV for cancer therapy.