Emerging therapies for melanoma

Substantial progress has been made in understanding the pathogenesis of malignant melanoma at the cellular level, leading to the development of several new agents in the treatment of melanoma. The focus of this review is to summarize the emerging therapies and investigational agents in the treatment of melanoma over the last 5 years.     

Emerging immunotherapies for metastasis

Major advances in cancer immunotherapy have dramatically expanded the potential to manipulate immune cells in cancer patients with metastatic disease to counteract cancer spread and extend patient lifespan. One of the most successful types of immunotherapy is the immune checkpoint inhibitors, such as anti-CTLA-4 and anti-PD-1, that keep anti-tumour T cells active. However, not every patient with metastatic disease benefits from this class of drugs and patients often develop resistance to these therapies over time. Tremendous research effort is now underway to uncover new immunotherapeutic targets that can be used in patients who are refractory to anti-CTLA-4 or anti-PD-1 treatment. Here, we discuss results from experimental model systems demonstrating that modulating the immune response can negatively affect metastasis formation. We focus on molecules that boost anti-tumour immune cells and opportunities to block immunosuppression, as well as cell-based therapies with enhanced tumour recognition properties for solid tumours. We also present a list of challenges in treating metastatic disease with immunotherapy that must be considered in order to move laboratory observations into clinical practice and maximise patient benefit.Subject terms: Tumour immunology, Immunotherapy, Tumour immunology     

The Multifaceted Roles of B Cells in Solid Tumors: Emerging Treatment Opportunities

The influence of tumor infiltrating lymphocytes on tumor growth and response to therapy is becoming increasingly apparent. While much work has focused on the role of T cell responses in anti-tumor immunity, the role of B cells in solid tumors is much less understood. Tumor infiltrating B cells have been found in a variety of solid tumors, including breast, ovarian, prostate, melanoma, and colorectal cancer. The function of B cells in solid tumors is controversial, with many studies reporting a pro-tumor effect, while other studies demonstrate a role for B cells in the anti-tumor immune response. In this review, we discuss the prognostic ability of B cells in solid tumors as well as the mechanisms by which B cells can either promote or suppress anti-tumor immunity. Additionally, we review current therapeutic strategies that may target both pro- and anti-tumor B cells.

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Emerging therapies for urothelial cancer

Urothelial carcinoma is one of the leading causes of death in Europe and the United States. Despite its chemosensitivity, median overall survival for advanced disease is still nearly 1 year. Most second-line chemotherapeutic agents tested have been disappointing. Thus, new treatment strategies are clearly needed. This review focuses on emerging therapies in urothelial carcinoma. Results from recent clinical trials, investigating the activity of new generation cytostatic agents, as well as results from studies assessing the toxicity and efficacy of novel targeted therapies, are discussed. In this setting, anti-epidermal growth factor receptor, angiogenesis, and phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitors account for the majority of phase I and II trials.     

Emerging technologies for HER2 testing

HER2-positive status is the sole criterion for identifying patients with breast cancer for Herceptin therapy, which has known efficacy in women with metastatic breast cancer (MBC). Immunohistochemistry (IHC) and fluorescence in-situ hybridization (FISH), which measure the HER2 protein and gene, respectively, are currently the most widely used HER2 tests in the clinical setting. However, results from these assays are influenced by many variables including choice of antibody or probe, methodology, level of user experience and interlaboratory variability. Although there is no widespread standard testing algorithm, the importance of HER2 in clinical practice demands accurate and reproducible tests. Polymerase chain reaction (PCR) and chromogenic in-situ hybridization (CISH) represent upcoming methods for assessing HER2 gene amplification. Enzyme-linked immunosorption assay (ELISA), a semi-automated technique that can be used to measure the level of the HER2 extracellular domain (ECD) in serum, may also prove useful. While such technologies show great promise, they will at least have to be validated against IHC or FISH before being accepted into routine clinical practice.     

Emerging therapeutic targets for synovial sarcoma

Synovial sarcoma is part of soft tissue sarcomas, an uncommon group of malignant tumors of mesenchymal origin. Unfortunately, a very limited number of useful drugs are active for most advanced synovial sarcoma. These tumors showed VEGF expression, and elevated serum VEGF levels correlate with higher histologic tumor grade. Inhibition of VEGFR was associated with tumor activity in preclinical models of synovial sarcoma and drugs such as sorafenib, pazopanib and bevacizumab have been employed in synovial sarcoma in monotherapy and in combination with chemotherapy. Other targets such as EGFR, HER2, IGFR-1R and mTOR have been exploited, but their inhibition by drugs such as gefitinib, trastuzumab, figitumumab, and temsirolimus, has not resulted in meaningful activity. Newer approaches include CXCR4 inhibition, immune-based therapies (NY-ESO-1), targeting epigenetic misregulation with HDAC inhibitors and targeting developmental pathways such Notch and Hedgehog. This review will summarize achievements and pitfalls of drugs against emerging therapeutic targets for synovial sarcoma.     

Emerging therapies for B-cell non-Hodgkin lymphoma

In recent years considerable progress has been made in the treatment of patients with B-cell non-Hodgkin lymphoma (NHL). Although responses can be achieved with combination chemotherapy regimens, a substantial proportion of patients are still not cured. In recent years, the knowledge of the cellular and molecular biology of distinct types of B-cell NHL have led to the development of a new class of drugs that specifically targets unique disease-specific pathways. This review will focus on novel therapies that are being developed for the treatment of B-cell NHL including those targeting the B-cell receptor signaling pathway, the proteasome, epigenetic lesions, novel anti-apoptotic drugs, new monoclonal antibodies and immunomodulatory drugs.     

Emerging targeted therapies for breast cancer

Breast cancer is the most common neoplasia among women in the world. For the last few years there has been an increasing interest in the development of agents against molecular targets considered to be involved in the process of malignant transformation or tumor progression. Experimental data indicate that various intracellular signaling pathways may be activated or overexpressed in patients who have breast cancer. Targeted therapies against these pathways have recently become one of the most active and promising areas of development in oncology.     

肿瘤干细胞蛋白质组学研究方法的新进展

蛋白质组学是应用多种技术手段来研究蛋白质组的一门新兴学科,它能鉴定干细胞分化中的各种信号转导复合物和通路。首先采用多种方式来获得足够的蛋白质组分析所需的肿瘤干细胞;其次采用亚细胞分离技术作为蛋白质组学分析的工具;进一步采用蛋白质组学方法鉴定肿瘤干细胞特异性蛋白;最后采用蛋白质组学方法搜索到新的治疗靶。新的干细胞培养技术和最新水平质谱分析使肿瘤干细胞研究进入了一个崭新阶段。因此应用蛋白质组学方法可以有效地阐明哪些通路参与调节肿瘤干细胞活化等多种分子进程,进一步鉴别和寻找单个分子作为生物标志物或治疗靶。     

Emerging targeted therapies for breast cancer

Targeted therapies offer a new approach to breast cancer treatment. Rather than eliminating both malignant and normal cells nonspecifically, these so-called "rational" therapies exploit second messenger proteins, ligands, and receptors that are known to be upregulated in neoplastic cells, or are implicated in cancer metastasis. This review will highlight a number of these targets and the mechanisms that have been targeted in drug design. We will also describe recently completed and currently ongoing clinical trials investigating targeted therapies and their potential to augment standard breast cancer therapy.