The Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway was discovered more than a quarter-century ago. As a fulcrum of many vital cellular processes, the JAK/STAT pathway constitutes a rapid membrane-to-nucleus signaling module and induces the expression of various critical mediators of cancer and inflammation. Growing evidence suggests that dysregulation of the JAK/STAT pathway is associated with various cancers and autoimmune diseases. In this review, we discuss the current knowledge about the composition, activation, and regulation of the JAK/STAT pathway. Moreover, we highlight the role of the JAK/STAT pathway and its inhibitors in various diseases.

Ovarian cancer is one of the leading causes of death in patients with gynecological malignancy. Despite optimal cytoreductive surgery and platinum-based chemotherapy, ovarian cancer disseminates and relapses frequently, with poor prognosis. Hence, it is urgent to find new targeted therapies for ovarian cancer. Recently, the tumor microenvironment has been reported to play a vital role in the tumorigenesis of ovarian cancer, especially with discoveries from genome-, transcriptome- and proteome-wide studies; thus tumor microenvironment may present potential therapeutic target for ovarian cancer. Here, we review the interactions between the tumor microenvironment and ovarian cancer and various therapies targeting the tumor environment.

Cancer cells resistance to various therapies remains to be a key challenge nowadays. For a long time, scientists focused on tumor cells themselves for the mechanisms of acquired drug resistance. However, recent evidence showed that tumor microenvironment (TME) is essential for regulating immune escape, drug resistance, progression and metastasis of malignant cells. Reciprocal interactions between cancer cells and non-malignant cells within this milieu often reshape the TME and promote drug resistance. Therefore, advanced knowledge about these sophisticated interactions is significant for the design of effective therapeutic approaches. In this review, we highlight cancer-associated fibroblasts (CAFs), tumor-associated macrophages (TAMs), tumor-associated neutrophils (TANs), myeloid-derived suppressor cells (MDSCs), T-regulatory lymphocytes (Tregs), mesenchymal stem cells (MSCs), cancer-associated adipocytes (CAAs), and tumor endothelial cells (TECs) existing in TME, as well as their multiple cross-talk with tumor cells, which eventually endows tumor cells with therapeutic resistance.

Advanced studies of microRNAs (miRNAs) have revealed their manifold biological functions, including control of cell proliferation, cell cycle and cell death. However, it seems that their roles as key regulators of metabolism have drawn more and more attention in the recent years. Cancer cells display increased metabolic autonomy in comparison to non-transformed cells, taking up nutrients and metabolizing them in pathways that support growth and proliferation. MiRNAs regulate cell metabolic processes through complicated mechanisms, including directly targeting key enzymes or transporters of metabolic processes and regulating transcription factors, oncogenes / tumor suppressors as well as multiple oncogenic signaling pathways. MiRNAs like miR-375, miR-143, miR-14 and miR-29b participate in controlling cancer cell metabolism by regulating the expression of genes whose protein products either directly regulate metabolic machinery or indirectly modulate the expression of metabolic enzymes, serving as master regulators, which will hopefully lead to a new therapeutic strategy for malignant cancer. This review focuses on miRNA regulations of cancer cell metabolism,including glucose uptake, glycolysis, tricarboxylic acid cycle and insulin production, lipid metabolism and amino acid biogenesis, as well as several oncogenic signaling pathways. Furthermore, the challenges of miRNA-based strategies for cancer diagnosis, prognosis and therapeutics have been discussed.

The poor prognosis for patients with advanced malignancy relates partly to the inability to reverse cancer metastasis. In this study we have investigated an integrated immunotherapy method against pre-established metastases in three kinds of advanced cancer models including B16 melanoma, 4T1 breast tumor, and Hca hepatoma. The progression of metastases into multistep lymph nodes (LN) and internal organs was, markedly impeded in the midway stage and reversed in the ultimate stage following a 20-day course of intravenous immunotherapy [with interleukin-12 (IL-12) gene-engineered mesenchymal stem cells (MSCs), administered once every 5 days P < 0.05)]; the therapy was without systemic toxic effects. As the control, obvious systemic toxicity was observed in the free AdIL-12 group, yet metastasis was partly delayed only in the midway stage but not in the ultimate stage. Enzyme-linked immunosorbent assay (ELISA) showed that the intratumoral expression levels of IL-12 were enhanced by cytokine-engineered MSCs to be tenfold greater than that of free AdIL-12 groups in the ultimate stage; conversely, free AdIL-12 groups showed elevated serum, but not intratumoral levels of IL-12, during the midway stage. Furthermore, histomorphometric analysis revealed a reductive tendency toward reversion of tumor-associated lymphatic sprouts and an increased tumor apoptosis index in engineered MSC groups (P < 0.05). These data indicate the potential of cytokine-engineered MSCs to be considered as an integrated therapeutic weapon for targeting advanced malignancies.

Advanced and recurrent gynecological cancers are associated with poor prognosis and lack of effective treatment. The developments of the molecular mechanisms on cancer progression provide insight into novel targeted therapies, which are emerging as groundbreaking and promising cancer treatment strategies. In gynecologic malignancies, potential therapeutic targeted agents include antiangiogenic agents, poly (ADP-ribose) polymerase (PARP) inhibitors, tumor-intrinsic signaling pathway inhibitors, selective estrogen receptor downregulators, and immune checkpoint inhibitors. In this article, we provide a comprehensive review of the clinical evidence of targeted agents in gynecological cancers and discuss the future implication.