Is It Time for a More Holistic Approach to the Treatment of Multiple Myeloma?

In the UK, approximately 5820 new cases of multiple myeloma (MM) are diagnosed each year. This number has increased by a third since the early 1990s. Considerable progress has been achieved in our ability to treat MM as a result of the development of new chemotherapeutic agents. MM is a disease more commonly seen in elderly individuals who frequently have pre-existing co-morbidities and are subject to social pressures that impact adversely on their quality of life (QOL). As their lives are extended by more effective treatment of MM, there is a greater need to address such issues. This review will focus on the holistic needs of a patient with MM, and how all members of the multidisciplinary team have a role. The aim is to advocate for centres to support MM patients to live well with their condition.

Anticancer Activity of Propolis and Its Compounds

Propolis is a natural material that honey bees (Apis mellifera) produce from various botanical sources. The therapeutic activity of propolis, including antibacterial, antifungal, and anti-inflammatory effects, have been known since antiquity. Cancer is one of the major burdens of disease worldwide, therefore, numerous studies are being conducted to develop new chemotherapeutic agents and treatments for cancer. Propolis is a rich source of biologically active compounds, which affect numerous signaling pathways regulating crucial cellular processes. The results of the latest research show that propolis can inhibit proliferation, angiogenesis, and metastasis of cancer cells and stimulate apoptosis. Moreover, it may influence the tumor microenvironment and multidrug resistance of cancers. This review briefly summarizes the molecular mechanisms of anticancer activity of propolis and its compounds and highlights the potential benefits of propolis to reduce the side effects of chemotherapy and radiotherapy.

Folate metabolism: a re-emerging therapeutic target in haematological cancers

Folate-mediated one carbon (1C) metabolism supports a series of processes that are essential for the cell. Through a number of interlinked reactions happening in the cytosol and mitochondria of the cell, folate metabolism contributes to de novo purine and thymidylate synthesis, to the methionine cycle and redox defence. Targeting the folate metabolism gave rise to modern chemotherapy, through the introduction of antifolates to treat paediatric leukaemia. Since then, antifolates, such as methotrexate and pralatrexate have been used to treat a series of blood cancers in clinic. However, traditional antifolates have many deleterious side effects in normal proliferating tissue, highlighting the urgent need for novel strategies to more selectively target 1C metabolism. Notably, mitochondrial 1C enzymes have been shown to be significantly upregulated in various cancers, making them attractive targets for the development of new chemotherapeutic agents. In this article, we present a detailed overview of folate-mediated 1C metabolism, its importance on cellular level and discuss how targeting folate metabolism has been exploited in blood cancers. Additionally, we explore possible therapeutic strategies that could overcome the limitations of traditional antifolates.

Secondary Metabolites from Saccharomyces cerevisiae Species with Anticancer Potential

Chemotherapeutic agents produce from numerous sources such as animals, plants and micro-organisms are derived from the natural products. Although the existing therapeutic pipeline lacks fungal-derived metabolites, but hundreds of secondary metabolites derived from fungi are known to be possible chemotherapies. Over the past three decades, several secondary metabolites such as flavonoids, alkaloids, phenolic and polyketides have been developed by Saccharomyces cerevisiae species with exciting activities that considered valued for the growth of new chemotherapeutic agents. Many secondary metabolites are protective compounds which prevent abiotic and biotic stresses, i.e. predation, infection, drought and ultraviolet. Though not taking part in a living cell’s central metabolism, secondary metabolites play an important role in the function of an organism. Nevertheless, due to slow biomass build-up and inadequate synthesis by the natural host the yield of secondary metabolites is low by direct isolation. A detailed comprehension of biosynthetic pathways for development of secondary metabolites are necessary for S. cerevisiae biotransformation. These metabolites have higher inhibitory effect, specificity among cancer and normal cells, and the mechanism of non-apoptotic cell killing. This study shows the significance of bioactive compounds produced by S. cerevisiae species with their possible activity and value in chemotherapeutic drugs pipeline. The isolation and alteration of these natural secondary metabolites would promote the development of chemotherapeutic drugs.

Glioblastoma: Pathogenesis and Current Status of Chemotherapy and Other Novel Treatments

Glioblastoma is one of the most common and detrimental forms of solid brain tumor, with over 10,000 new cases reported every year in the United States. Despite aggressive multimodal treatment approaches, the overall survival period is reported to be less than 15 months after diagnosis. A widely used approach for the treatment of glioblastoma is surgical removal of the tumor, followed by radiotherapy and chemotherapy. While there are several drugs available that are approved by the Food and Drug Administration (FDA), significant efforts have been made in recent years to develop new chemotherapeutic agents for the treatment of glioblastoma. This review describes the molecular targets and pathogenesis as well as the current progress in chemotherapeutic development and other novel therapies in the clinical setting for the treatment of glioblastoma.

Heterobimetallic Ru(ii)/Fe(ii) complexes as potent anticancer agents against breast cancer cells, inducing apoptosis through multiple targets

Antimetastatic activity, high selectivity and cytotoxicity for human tumor cell lines make ruthenium(ii) complexes attractive for the development of new chemotherapeutic agents for cancer treatment.

Small Molecule Inhibitors of HSF1-Activated Pathways as Potential Next-Generation Anticancer Therapeutics

Targeted therapy is an emerging paradigm in the development of next-generation anticancer drugs. Heat shock factor 1 (HSF1) has been identified as a promising drug target because it regulates several pathways responsible for cancer cell growth, metastasis, and survival. Studies have clearly demonstrated that HSF1 is an effective drug target. Herein, we provide a concise yet comprehensive and integrated overview of progress in developing small molecule inhibitors of HSF1 as next-generation anticancer chemotherapeutics while critically evaluating their potential and challenges. We believe that this review will provide a better understanding of important concepts helpful for outlining the strategy to develop new chemotherapeutic agents with promising anticancer activities by targeting HSF1.