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Seminars in Cancer Biology

Wei Wang, Raju Kandimalla, Hao Huang, Lina Zhu, Ying Li, Feng Gao, Ajay Goel, Xin Wang
Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths worldwide. Similar to many other malignancies, CRC is a heterogeneous disease, making it a clinical challenge for optimization of treatment modalities in reducing the morbidity and mortality associated with this disease. A more precise understanding of the biological properties that distinguish patients with colorectal tumors, especially in terms of their clinical features, is a key requirement towards a more robust, targeted-drug design, and implementation of individualized therapies...
May 15, 2018: Seminars in Cancer Biology
Djordje Atanackovic, Tim Luetkens
In the past few years we have seen remarkable paradigm shifts in the treatment of many solid tumors due to the introduction of inhibitors targeting immune checkpoints such as PD-1/PD-L1 and CTLA-4. Recent results indicate that checkpoint inhibition also represents a very promising approach for certain types of hematologic malignancies. Unfortunately, treatment with checkpoint inhibitors is also associated with substantial toxicities and high costs and only a subset of patients appears to derive clinical benefit from these treatments...
May 15, 2018: Seminars in Cancer Biology
Giuseppe Curigliano
In gynecological cancers tumor infiltrating lymphocytes and upregulation of immune-related gene signatures have been associated with a better prognosis. Knowledge of tumor immunogenicity and associated gene signatures suggests that the tumor immune landscape is a key determinant to define patient prognosis and potentially to predict response to immune-checkpoint inhibitors. The aim of this review is to give an overview of immune gene signatures across gynecology histological cancer types, defining their prognostic and potential predictive role...
May 15, 2018: Seminars in Cancer Biology
Dingxiao Zhang, Dean G Tang, Kiera Rycaj
It is becoming increasingly clear that virtually all types of human cancers harbor a small population of stem-like cancer cells (i.e., cancer stem cells, CSCs). These CSCs preexist in primary tumors, can self-renew and are more tolerant of standard treatments, such as antimitotic and molecularly targeted agents, most of which preferentially eliminate differentiated and proliferating cancer cells. CSCs are therefore postulated as the root of therapy resistance, relapse and metastasis. Aside from surgery, radiation, and chemotherapy, immunotherapy is now established as the fourth pillar in the therapeutic armamentarium for patients with cancer, especially late-stage and advanced cancers...
May 9, 2018: Seminars in Cancer Biology
Maggie Haitian Wang, Heather J Cordell, Kristel Van Steen
Genome-wide association studies (GWAS) detect common genetic variants associated with complex disorders. With their comprehensive coverage of common single nucleotide polymorphisms and comparatively low cost, GWAS are an attractive tool in the clinical and commercial genetic testing. This review introduces the pipeline of statistical methods used in GWAS analysis, from data quality control, association tests, population structure control, interaction effects and results visualization, through to post-GWAS validation methods and related issues...
May 1, 2018: Seminars in Cancer Biology
Shuai Jiang, Zhi Yang, Shouyin Di, Wei Hu, Zhiqiang Ma, Fulin Chen, Yang Yang
Forkhead box O (FOXO) family has recently been highlighted as important transcriptional regulators associated with many diverse carcinomas. Although redundant functionality between FOXO family members with cancer is known, regulatory ability of FOXO4 for tumorigenesis and tumor metastasis is still on the way. FOXO4 significantly regulates cell cycle, resists oxidative stress, and responses to hypoxia. FOXO4 alteration is closely linked to the progression of human cancer. In this review, we introduce the regulation of FOXO4 in physiological and pathological conditions...
April 29, 2018: Seminars in Cancer Biology
Tobias Gutting, Elke Burgermeister, Nicolai Härtel, Matthias P Ebert
Immunotherapy is the latest revolution in cancer therapy. It continues to show impressive results in malignancies like melanoma and others. At least so far, effects are modest in colorectal cancer (CRC) and only a subset of patients benefits from already approved checkpoint inhibitors. In this review, we discuss major hurdles of immunotherapy like the immunosuppressive niche and low immunogenicity of CRC next to current achievements of checkpoint inhibitors, interleukin treatment and adoptive cell transfer (dendritic cells/cytokine induced killer cells, tumor infiltrating lymphocytes, chimeric antigen receptor cells, T cell receptor transfer) in pre-clinical models and clinical trials...
April 28, 2018: Seminars in Cancer Biology
Jeffery Ho, Xianchun Li, Lin Zhang, Yonghao Liang, Wei Hu, Johnny C W Yau, Hung Chan, Tony Gin, Matthew T V Chan, Gary Tse, William K K Wu
Malignancy of the pancreas is a leading cause of cancer-related mortality, with the highest case-fatality of all cancers. Nevertheless, the lack of sensitive biomarkers and presence of biological heterogeneity precludes its early detection and effective treatment. The recent introduction of next-generation sequencing allows characterization of multiple driver mutations at genome- and exome-wide levels. Sequencing of DNA and RNA from circulating tumour cells has also opened an exciting era of non-invasive procedures for tumour detection and prognostication...
April 25, 2018: Seminars in Cancer Biology
Bi Ning Zhang, Andrés Bueno Venegas, Ian D Hickson, Wai Kit Chu
Genome instability and cell cycle dysregulation are commonly associated with cancer. DNA replication stress driven by oncogene activation during tumorigenesis is now well established as a source of genome instability. Replication stress generates DNA damage not only during S phase, but also in the subsequent mitosis, where it impacts adversely on chromosome segregation. Some regions of the genome seem particularly sensitive to replication stress-induced instability; most notably, chromosome fragile sites. In this article, we review some of the important issues that have emerged in recent years concerning DNA replication stress and fragile site expression, as well as how chromosome instability is minimized by a family of ring-shaped protein complexes known as SMC proteins...
April 21, 2018: Seminars in Cancer Biology
Chong T Luo, Ming O Li
The evolutionally conserved forkhead box O (Foxo) family of transcription factors is pivotal in the control of nutrient sensing and stress responses. Recent studies have revealed that the Foxo proteins have been rewired to regulate highly specialized T cell activities. Here, we review the latest advances in the understanding of how Foxo transcription factors control T cell biology, including T cell trafficking, naive T cell homeostasis, effector and memory responses, as well as the differentiation and function of regulatory T cells...
April 20, 2018: Seminars in Cancer Biology
Tianzuo Zhan, Niklas Rindtorff, Johannes Betge, Matthias P Ebert, Michael Boutros
CRISPR/Cas9 has become a powerful method for making changes to the genome of many organisms. First discovered in bacteria as part of an adaptive immune system, CRISPR/Cas9 and modified versions have found a widespread use to engineer genomes and to activate or to repress the expression of genes. As such, CRISPR/Cas9 promises to accelerate cancer research by providing an efficient technology to dissect mechanisms of tumorigenesis, identify targets for drug development, and possibly arm cells for cell-based therapies...
April 16, 2018: Seminars in Cancer Biology
Chi Chun Wong, Weilin Li, Bertina Chan, Jun Yu
Altered epigenetic regulation is central to many human diseases, including cancer. Over the past two decade, major advances have been made in our understanding of the role of epigenetic alterations in carcinogenesis, particularly for DNA methylation, histone modifications and non-coding RNAs. Aberrant hypermethylation of DNA at CpG islands is a well-established phenomenon that mediates transcriptional silencing of tumor suppressor genes, and it is an early event integral to gastrointestinal cancer development...
April 14, 2018: Seminars in Cancer Biology
Seema Shah, Ethan J Brock, Kyungmin Ji, Raymond R Mattingly
Ras oncoproteins play pivotal roles in both the development and maintenance of many tumor types. Unfortunately, these proteins are difficult to directly target using traditional pharmacological strategies, in part due to their lack of obvious binding pockets or allosteric sites. This obstacle has driven a considerable amount of research into pursuing alternative ways to effectively inhibit Ras, examples of which include inducing mislocalization to prevent Ras maturation and inactivating downstream proteins in Ras-driven signaling pathways...
April 3, 2018: Seminars in Cancer Biology
Hidewaki Nakagawa, Masashi Fujita, Akihiro Fujimoto
Liver cancer is the third leading cause of cancer-related death worldwide. Some thousands of liver cancer genome have been sequenced globally so far and most of driver genes/mutations with high frequency are established in liver cancer, including Wnt/β-catenin pathway, TP53/cell-cycle pathways, telomere maintenance, and chromatin regulators. HBV integration into cancer-related genes is also a driver event in hepatocarcinogenesis. These genes are affected by structural variants, copy-number alterations and virus integrations as well as point mutations...
March 29, 2018: Seminars in Cancer Biology
Grégory Noël, Mireille Langouo Fontsa, Karen Willard-Gallo
The role of adaptive immunity is increasingly recognized as an important element both in the process of tumorigenesis and in the patient's response to treatment. While this understanding has led to new therapeutic strategies that potentiate the activities of tumor infiltrating lymphocytes, only a minority of patients attain durable responses. Metabolic activities in the tumor microenvironment, including hypoxia and acidity, can adversely affect immune responses, making the identification of metabolic biomarkers critically important for understanding and employing immunotherapies...
March 21, 2018: Seminars in Cancer Biology
Abdul Q Khan, Shilpa Kuttikrishnan, Kodappully S Siveen, Kirti S Prabhu, Muralitharan Shanmugakonar, Hamda A Al-Naemi, Mohammad Haris, Said Dermime, Shahab Uddin
Abnormally activated RAS proteins are the main oncogenic driver that governs the functioning of major signaling pathways involved in the initiation and development of human malignancies. Mutations in RAS genes and or its regulators, most frequent in human cancers, are the main force for incessant RAS activation and associated pathological conditions including cancer. In general, RAS is the main upstream regulator of the highly conserved signaling mechanisms associated with a plethora of important cellular activities vital for normal homeostasis...
March 7, 2018: Seminars in Cancer Biology
Keesha E Erickson, Oleksii S Rukhlenko, Richard G Posner, William S Hlavacek, Boris N Kholodenko
RAS is the most frequently mutated gene across human cancers, but developing inhibitors of mutant RAS has proven to be challenging. Given the difficulties of targeting RAS directly, drugs that impact the other components of pathways where mutant RAS operates may potentially be effective. However, the system-level features, including different localizations of RAS isoforms, competition between downstream effectors, and interlocking feedback and feed-forward loops, must be understood to fully grasp the opportunities and limitations of inhibiting specific targets...
March 5, 2018: Seminars in Cancer Biology
Jakob Nikolas Kather, Niels Halama, Dirk Jaeger
Colorectal cancer (CRC) is a common and lethal disease with a high therapeutic need. For most patients with metastatic CRC, chemotherapy is the only viable option. Currently, immunotherapy is restricted to the particular genetic subgroup of mismatch-repair deficient (MMRd)/microsatellite instable (MSI) CRC. Anti-PD1 therapy was recently FDA-approved as a second-line treatment in this subgroup. However, in a metastatic setting, these MMRd/MSI tumors are vastly outnumbered by mismatch-repair proficient (MMRp)/microsatellite stable (MSS) tumors...
March 1, 2018: Seminars in Cancer Biology
Ruth Nussinov, Chung-Jung Tsai, Hyunbum Jang
Ras signaling initiates at the plasma membrane. Thus, Ras behavior at the membrane and how it relates to its interactions with Raf and PI3Kα, are of immense interest. Here we review factors influencing Ras lateral diffusion. We then ask whether oncogenic Ras diffusion speed in the membrane is important for signaling response times and whether it affects ubiquitously all pathways. We suggest that if Ras expression is sufficiently high to dimerize (or form nanoclusters), signaling response of those pathways where dimers (or nanoclusters) are involved corresponds to the speed with which Ras molecules travel in the membrane...
February 27, 2018: Seminars in Cancer Biology
Nikee Awasthee, Vipin Rai, Srinivas Chava, Palanisamy Nallasamy, Ajaikumar B Kunnumakkara, Anupam Bishayee, Subhash C Chauhan, Kishore B Challagundla, Subash C Gupta
The inhibitory kappa B kinases (IKKs) and IKK related kinases are crucial regulators of the pro-inflammatory transcription factor, nuclear factor kappa B (NF-κB). The dysregulation in the activities of these kinases has been reported in several cancer types. These kinases are known to regulate survival, proliferation, invasion, angiogenesis, and metastasis of cancer cells. Thus, IKK and IKK related kinases have emerged as an attractive target for the development of cancer therapeutics. Several IKK inhibitors have been developed, few of which have advanced to the clinic...
February 24, 2018: Seminars in Cancer Biology
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