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Advances in Cancer Research

Christopher J Clarke
For many years, neutral sphingomyelinases (N-SMases) were long thought to be anticancer enzymes owing to their roles as key producers of ceramide linked to apoptosis, growth arrest, and the chemotherapeutic response. However, in recent years, with the cloning of multiple isoforms and with new information on their cellular roles, particularly for nSMase2, a more complex picture is emerging suggesting that N-SMases have both pro- and anticancer roles. In this chapter, we will summarize current knowledge on N-SMase expression in cancer and the roles of N-SMase activity and specific isoforms in cancer-relevant biologies...
2018: Advances in Cancer Research
Giovanni D'Angelo, Sitapriya Moorthi, Chiara Luberto
Sphingomyelin (SM) biosynthesis represents a complex, finely regulated process, mostly occurring in vertebrates. It is intimately linked to lipid transport and it is ultimately carried out by two enzymes, SM synthase 1 and 2, selectively localized in the Golgi and plasma membrane. In the course of the SM biosynthetic reaction, various lipids are metabolized. Because these lipids have both structural and signaling functions, the SM biosynthetic process has the potential to affect diverse important cellular processes (such as cell proliferation, cell survival, and migration)...
2018: Advances in Cancer Research
Falak Patel, Stefka D Spassieva
Cancer patients' quality of life is greatly dependent on the efficacy of treatments and their associated side effects, which can significantly reduce the overall quality of life. Although the effectiveness of cancer treatments has improved over time, adverse effects persist with each treatment. Some side effects, such as paclitaxel-induced peripheral neuropathy, can be dose limiting, thus further reducing the potential of paclitaxel chemotherapy treatment. Premature ovarian failure in young female patients due to radiation and chemotherapy therapy can have devastating infertility consequences...
2018: Advances in Cancer Research
Jeremy Shaw, Pedro Costa-Pinheiro, Logan Patterson, Kelly Drews, Sarah Spiegel, Mark Kester
Sphingolipids are bioactive lipids that participate in a wide variety of biological mechanisms, including cell death and proliferation. The myriad of pro-death and pro-survival cellular pathways involving sphingolipids provide a plethora of opportunities for dysregulation in cancers. In recent years, modulation of these sphingolipid metabolic pathways has been in the forefront of drug discovery for cancer therapeutics. About two decades ago, researchers first showed that standard of care treatments, e.g., chemotherapeutics and radiation, modulate sphingolipid metabolism to increase endogenous ceramides, which kill cancer cells...
2018: Advances in Cancer Research
Clayton S Lewis, Christina Voelkel-Johnson, Charles D Smith
Sphingosine kinases (SK1 and SK2) are key, druggable targets within the sphingolipid metabolism pathway that promote tumor growth and pathologic inflammation. A variety of isozyme-selective and dual inhibitors of SK1 and SK2 have been described in the literature, and at least one compound has reached clinical testing in cancer patients. In this chapter, we will review the rationale for targeting SKs and summarize the preclinical and emerging clinical data for ABC294640 as the first-in-class selective inhibitor of SK2...
2018: Advances in Cancer Research
Megan M Young, Hong-Gang Wang
Macroautophagy (herein referred to as autophagy) is a highly conserved stress response that engulfs damaged proteins, lipids, and/or organelles within double-membrane vesicles called autophagosomes for lysosomal degradation. Dysregulated autophagy is a hallmark of cancer; and thus, there is great interest in modulating autophagy for cancer therapy. Sphingolipids regulate each step of autophagosome biogenesis with roles for sphingolipid metabolites and enzymes spanning from the initial step of de novo ceramide synthesis to the sphingosine-1-phosphate lyase 1-mediated exit from the sphingolipid pathway...
2018: Advances in Cancer Research
Christina Voelkel-Johnson, James S Norris, Shai White-Gilbertson
Sphingolipid metabolism is known to play a role in cell death, survival, and therapy resistance in cancer. Sphingolipids, particularly dihydroceramide and ceramide, are associated with antiproliferative or cell death responses, respectively, and are central to effective cancer therapy. Within the last decade, strides have been made in elucidating many intricacies of sphingolipid metabolism. New information has emerged on the mechanisms by which sphingolipid metabolism is dysregulated during malignancy and how cancer cells survive and/or escape therapeutic interventions...
2018: Advances in Cancer Research
Samy A F Morad, Myles C Cabot
Chemotherapy resistance, inherent or acquired, represents a serious barrier to the successful treatment of cancer. Although drug efflux, conducted by plasma membrane-resident proteins, detoxification enzymes, cell death inhibition, and DNA damage repair are ensemble players in this unwanted biology, a full understanding of the many in concert molecular mechanisms driving drug resistance is lacking. Recent discoveries in sphingolipid (SL) metabolism have provided significant insight into the role of these lipids in cancer growth; however, considerably less is known with respect to SLs and the drug-resistant phenotype...
2018: Advances in Cancer Research
Antonio Gomez-Muñoz
Ceramide 1-phosphate (C1P) is a pleiotropic bioactive sphingolipid metabolite capable of regulating key physiologic cell functions and promoting pathologic processes. Concerning pathology, C1P or ceramide kinase (CerK), the enzyme responsible for its biosynthesis in mammalian cells, has been implicated in cancer cell growth, survival, and dissemination and is involved in inflammatory responses associated with different types of cancer cells. The mechanisms or signaling pathways mediating these C1P actions have only been partially described...
2018: Advances in Cancer Research
Kristen A Jeffries, Natalia I Krupenko
Ceramides, important players in signal transduction, interact with multiple cellular pathways, including p53 pathways. However, the relationship between ceramide and p53 is very complex, and mechanisms underlying their coregulation are diverse and not fully characterized. The role of p53, an important cellular regulator and a transcription factor, is linked to its tumor suppressor function. Ceramides are involved in the regulation of fundamental processes in cancer cells including cell death, proliferation, autophagy, and drug resistance...
2018: Advances in Cancer Research
Mariana Nikolova-Karakashian
Nonalcoholic fatty liver disease (NAFLD) is a group of liver disorders encompassing simple hepatic steatosis and its more aggressive forms of nonalcoholic steatohepatitis and cirrhosis. It is a rapidly growing health concern and the major cause for the increasing incidence of primary liver tumors. Unequivocal evidence shows that sphingolipid metabolism is altered in the course of the disease and these changes might contribute to NAFLD progression. Recent data provide solid support to the notion that deregulated ceramide and sphingosine-1-phosphate metabolism are present at all stages of NAFLD, i...
2018: Advances in Cancer Research
Ahmed Elsherbini, Erhard Bieberich
Exosomes are secreted extracellular vesicles (EVs) that carry micro RNAs and other factors to reprogram cancer cells and tissues affected by cancer. Exosomes are exchanged between cancer cells and other tissues, often to prepare a premetastatic niche, escape immune surveillance, or spread multidrug resistance. Only a few studies investigated the function of lipids in exosomes although their lipid composition is different from that of the secreting cells. Ceramide is one of the lipids critical for exosome formation, and it is also enriched in these EVs...
2018: Advances in Cancer Research
Rose Nganga, Natalia Oleinik, Besim Ogretmen
Mechanistic details for the roles of sphingolipids and their downstream targets in the regulation of tumor growth, response to chemo/radiotherapy, and metastasis have been investigated in recent studies using innovative molecular, genetic and pharmacologic tools in various cancer models. Induction of ceramide generation in response to cellular stress by chemotherapy, radiation, or exogenous ceramide analog drugs mediates cell death via apoptosis, necroptosis, or mitophagy. In this chapter, distinct functions and mechanisms of action of endogenous ceramides with different fatty acyl chain lengths in the regulation of cancer cell death versus survival will be discussed...
2018: Advances in Cancer Research
Ann-Marie Broome
No abstract text is available yet for this article.
2018: Advances in Cancer Research
Lance Dockery, Marie-Christine Daniel
This chapter reviews the use of dendronized systems as nanocarriers for the delivery of chemotherapeutic drugs. Dendronized systems include dendrimers prepared through convergent methods as well as other systems containing dendrons (e.g., polymers, nanoparticles, liposomes). The preparation of such systems is detailed, followed by the various conjugation techniques used for the transport of chemotherapeutic drugs and their specific delivery to tumor cells. In addition, the ability of dendronized systems to provide passive and active targeting to tumors is discussed...
2018: Advances in Cancer Research
Al de Leon, Reshani Perera, Pinunta Nittayacharn, Michaela Cooley, Olive Jung, Agata A Exner
Ultrasound is the second most utilized imaging modality in the world because it is widely accessible, robust, and safe. Aside from its extensive use in diagnostic imaging, ultrasound has also been frequently utilized in therapeutic applications. Particularly, when combined with appropriate delivery systems, ultrasound provides a flexible platform for simultaneous real-time imaging and triggered release, enabling precise, on-demand drug delivery to target sites. This chapter will discuss the basics of ultrasound including its mechanism of action and how it can be used to trigger the release of encapsulated drug either through thermal or cavitation effects...
2018: Advances in Cancer Research
C Tilden Hagan, Yusra B Medik, Andrew Z Wang
Cancer immunotherapy is a powerful, growing treatment approach to cancer that can be combined with chemotherapy, radiotherapy, and oncosurgery. Modulating the immune system to enhance anticancer response by several strategies has yielded improved cancer survival. Despite this progress, the success rate for immunotherapy has been below expectations due to unpredictable efficacy and off-target side effects from systemic dosing. Nanotechnology offers numerous different materials and targeting properties to overcome many of these challenges in immunotherapy...
2018: Advances in Cancer Research
Linmei Li, Shiqiang Yan, Bingcheng Lin, Qihui Shi, Yao Lu
Cancer immunotherapy fights against cancer by modulating the immune response and is delivering encouraging results in clinical treatments. However, it is challenging to achieve durable response in all cancer patients during treatment due to the diversity and dynamic nature of immune system as well as inter- and intratumor heterogeneity. A comprehensive assessment of system immunity and tumor microenvironment is crucial for effective and safe cancer therapy, which can potentially be resolved by single-cell proteomic analysis...
2018: Advances in Cancer Research
Dean M Connor, Ann-Marie Broome
Gold nanoparticles (Au NPs) are very attractive and versatile nanoparticles since they have a remarkable capacity to absorb and scatter light, convert optical energy into heat via nonradiative electron relaxation dynamics, and surface chemistries that can be capitalized upon so that the nanoparticles act as drug carriers. Au NPs have excellent stability and biocompatibility, tailorable shapes and sizes, an easily functionalized surface, high drug-loading capacity, and low toxicity. The properties of Au NPs can be leveraged to develop more precisely targeted and effective cancer therapeutics...
2018: Advances in Cancer Research
Shiqun Shao, Min Xue
Supramolecular interactions, such as those observed between antibodies and antigens, have been employed in developing analytical methods for several decades. One major area of interest concerns cancer research, where intricate supramolecular designs have emerged to tackle difficult analytes in complex tumor systems. Our increasing knowledge toward supramolecular systems have elicited profound interest in creating more efficient analytical approaches, evidenced by the ever-growing body of literature in the field...
2018: Advances in Cancer Research
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