Biomarkers for checkpoint inhibition in hematologic malignancies
Publication date: Available online 18 June 2018 Source:Seminars in Cancer Biology Author(s): 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 cl...
Source: Seminars in Cancer Biology - June 19, 2018 Category: Cancer & Oncology Source Type: research

Emerging Trends in Biomarker Discovery: Ease of Prognosis and Prediction in Cancer
Publication date: Available online 29 May 2018 Source:Seminars in Cancer Biology Author(s): Anil K. Sharma (Source: Seminars in Cancer Biology)
Source: Seminars in Cancer Biology - May 30, 2018 Category: Cancer & Oncology Source Type: research

Implementing Precision Cancer Medicine in the Genomic Era
Publication date: Available online 30 May 2018 Source:Seminars in Cancer Biology Author(s): Hui-Zi Chen, Russell Bonneville, Sameek Roychowdhury The utilization of genomic data to direct treatment for cancer patients represents the central tenet in precision oncology, in which a patient is matched to a specific drug or therapy based on the genetic drivers detected in his or her tumor rather than the tumor’s histologic classification. The expected but not always realized outcomes of molecularly matched therapies include increased response rates, more durable responses, deeper responses, and decreased number of therap...
Source: Seminars in Cancer Biology - May 30, 2018 Category: Cancer & Oncology Source Type: research

Gyneco-oncological genomics and emerging biomarkers for cancer treatment with immune-checkpoint inhibitors
Publication date: Available online 27 May 2018 Source:Seminars in Cancer Biology Author(s): 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 prognost...
Source: Seminars in Cancer Biology - May 28, 2018 Category: Cancer & Oncology Source Type: research

Emerging biomarkers for immune checkpoint inhibition in lung cancer
Publication date: Available online 19 May 2018 Source:Seminars in Cancer Biology Author(s): George Cyriac, Leena Gandhi Immune checkpoint inhibition with anti-PD-1 therapy has been notably successful in non-small cell lung cancer (NSCLC) and changed standard practice in multiple settings. However, despite some durable benefits seen, the majority of unselected patients with NSCLC fail to respond to checkpoint inhibitors. Patient selection is crucial and will become even more important in the development of combination therapies with immune checkpoint inhibitors. PD-L1 expression by immunohistochemistry (IHC) has emerged as...
Source: Seminars in Cancer Biology - May 20, 2018 Category: Cancer & Oncology Source Type: research

Clinical applications of gut microbiota in cancer biology
Publication date: Available online 18 May 2018 Source:Seminars in Cancer Biology Author(s): Sunny H. Wong, Thomas N.Y. Kwong, Chun-Ying Wu, Jun Yu The involvement of microorganisms in cancer has been increasing recognized. Collectively, microorganisms have been estimated to account for ~20% of all cancers worldwide. Recent advances in metagenomics and bioinformatics have provided new insights on the microbial ecology in different tumors, pinpointing the roles of microorganisms in cancer formation, development and response to treatments. Furthermore, studies have emphasized the importance of host-microbial and inter-microb...
Source: Seminars in Cancer Biology - May 19, 2018 Category: Cancer & Oncology Source Type: research

Molecular subtyping of colorectal cancer: Recent progress, new challenges and emerging opportunities
Publication date: Available online 18 May 2018 Source:Seminars in Cancer Biology Author(s): 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 featu...
Source: Seminars in Cancer Biology - May 19, 2018 Category: Cancer & Oncology Source Type: research

Cancer stem cells: regulation programs, immunological properties and immunotherapy
Publication date: Available online 9 May 2018 Source:Seminars in Cancer Biology Author(s): 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 f...
Source: Seminars in Cancer Biology - May 10, 2018 Category: Cancer & Oncology Source Type: research

CRISPR/Cas9 for cancer research and therapy
We describe novel Cas9 variants and how they are used in functional genomics to discover novel cancer-specific vulnerabilities. Furthermore, we highlight the impact of CRISPR/Cas9 in generating organoid and mouse models of cancer. Finally, we provide an overview of the first clinical trials that apply CRISPR/Cas9 as a therapeutic approach against cancer. (Source: Seminars in Cancer Biology)
Source: Seminars in Cancer Biology - May 5, 2018 Category: Cancer & Oncology Source Type: research

Foxo transcription factors in T cell biology and tumor immunity
Publication date: Available online 21 April 2018 Source:Seminars in Cancer Biology Author(s): 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 fun...
Source: Seminars in Cancer Biology - May 5, 2018 Category: Cancer & Oncology Source Type: research

DNA replication stress and its impact on chromosome segregation and tumorigenesis
Publication date: Available online 23 April 2018 Source:Seminars in Cancer Biology Author(s): 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 insta...
Source: Seminars in Cancer Biology - May 5, 2018 Category: Cancer & Oncology Source Type: research

Translational genomics in pancreatic ductal adenocarcinoma: A review with re-analysis of TCGA dataset
Publication date: Available online 26 April 2018 Source:Seminars in Cancer Biology Author(s): 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-...
Source: Seminars in Cancer Biology - May 5, 2018 Category: Cancer & Oncology Source Type: research

Novel role of forkhead box O 4 transcription factor in cancer: Bringing out the good or the bad
Publication date: Available online 30 April 2018 Source:Seminars in Cancer Biology Author(s): 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 progressio...
Source: Seminars in Cancer Biology - May 5, 2018 Category: Cancer & Oncology Source Type: research

Checkpoints and beyond – Immunotherapy in colorectal cancer
Publication date: Available online 30 April 2018 Source:Seminars in Cancer Biology Author(s): 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 inhibitor...
Source: Seminars in Cancer Biology - May 5, 2018 Category: Cancer & Oncology Source Type: research

Statistical methods for genome-wide association studies
Publication date: Available online 1 May 2018 Source:Seminars in Cancer Biology Author(s): 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 visu...
Source: Seminars in Cancer Biology - May 5, 2018 Category: Cancer & Oncology Source Type: research

Epigenomic biomarkers for prognostication and diagnosis of gastrointestinal cancers
Publication date: Available online 14 April 2018 Source:Seminars in Cancer Biology Author(s): 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 gastroint...
Source: Seminars in Cancer Biology - April 15, 2018 Category: Cancer & Oncology Source Type: research

Ras and Rap1: A Tale of Two GTPases
Publication date: Available online 3 April 2018 Source:Seminars in Cancer Biology Author(s): 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...
Source: Seminars in Cancer Biology - April 4, 2018 Category: Cancer & Oncology Source Type: research

Genome Sequencing Analysis of Liver Cancer for Precision Medicine
Publication date: Available online 29 March 2018 Source:Seminars in Cancer Biology Author(s): 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 varia...
Source: Seminars in Cancer Biology - March 29, 2018 Category: Cancer & Oncology Source Type: research

Cancer molecular markers: A guide to cancer detection and management
Publication date: Available online 8 February 2018 Source:Seminars in Cancer Biology Author(s): Meera Nair, Sardul Singh Sandhu, Anil Kumar Sharma Cancer is generally caused by the molecular alterations which lead to specific mutations. Advances in molecular biology have provided an impetus to the study of cancers with valuable prognostic and predictive significance. Over the hindsight various attempts have been undertaken by scientists worldwide, in the management of cancer; where, we have witnessed a number of molecular markers which allow the early detection of cancers and lead to a decrease in its mortality rate. Rece...
Source: Seminars in Cancer Biology - March 22, 2018 Category: Cancer & Oncology Source Type: research

The Impact of Tumor Cell Metabolism on T Cell-Mediated Immune Responses and Immuno-Metabolic Biomarkers in Cancer
Publication date: Available online 21 March 2018 Source:Seminars in Cancer Biology Author(s): 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 re...
Source: Seminars in Cancer Biology - March 21, 2018 Category: Cancer & Oncology Source Type: research

P21 activated kinase signaling in cancer
Publication date: Available online 9 January 2018 Source:Seminars in Cancer Biology Author(s): Chetan K. Rane, Audrey Minden The p21 Activated Kinases (PAKs) are a family of serine threonine kinases, that consist of 6 members, PAKs 1–6, which are positioned at an intersection of multiple signaling pathways implicated in oncogenesis. The PAKs were originally identified as protein kinases that function downstream of the Ras related Rho GTPases Cdc42 and Rac. PAK1 and PAK4, which belong to Group I and Group II PAKs, respectively, are most often associated with tumorigenesis. On account of their well characterized roles...
Source: Seminars in Cancer Biology - March 17, 2018 Category: Cancer & Oncology Source Type: research

Epigenetics of breast cancer: Biology and clinical implication in the era of precision medicine
Publication date: Available online 12 January 2018 Source:Seminars in Cancer Biology Author(s): Barbara Pasculli, Raffaela Barbano, Paola Parrella In the last years, mortality from breast cancer has declined in western countries as a consequence of a more widespread screening resulting in earlier detection, as well as an improved molecular classification and advances in adjuvant treatment. Nevertheless, approximately one third of breast cancer patients will develop distant metastases and eventually die for the disease. There is now a compelling body of evidence suggesting that epigenetic modifications comprising DNA methy...
Source: Seminars in Cancer Biology - March 17, 2018 Category: Cancer & Oncology Source Type: research

Intratumor heterogeneity in epigenetic patterns
Publication date: Available online 31 January 2018 Source:Seminars in Cancer Biology Author(s): Yassen Assenov, David Brocks, Clarissa Gerhäuser Analogous to life on earth, tumor cells evolve through space and time and adapt to different micro-environmental conditions. As a result, tumors are composed of millions of genetically diversified cells at the time of diagnosis. Profiling these variants contributes to understanding tumors’ clonal origins and might help to better understand response to therapy. However, even genetically homogenous cell populations show remarkable diversity in their response to different...
Source: Seminars in Cancer Biology - March 17, 2018 Category: Cancer & Oncology Source Type: research

Homeostatic interplay between FoxO proteins and ER proteostasis in cancer and other diseases
Publication date: Available online 31 January 2018 Source:Seminars in Cancer Biology Author(s): Matías González-Quiroz, Hery Urra, Celia María Limia, Claudio Hetz Cancer cells are exposed to adverse conditions within the tumor microenvironment that challenge cells to adapt and survive. Several of these homeostatic perturbations insults alter the normal function of the endoplasmic reticulum (ER), resulting in the accumulation of misfolded proteins. ER stress triggers a conserved signaling pathway known as the unfolded protein response (UPR) to cope with the stress or trigger apoptosis of damaged cells....
Source: Seminars in Cancer Biology - March 17, 2018 Category: Cancer & Oncology Source Type: research

New biomarkers for diagnosis and prognosis of localized prostate cancer
Publication date: Available online 31 January 2018 Source:Seminars in Cancer Biology Author(s): Dimitry A. Chistiakov, Veronika A. Myasoedova, Andrey V. Grechko, Alexandra A. Melnichenko, Alexander N. Orekhov The diagnostics and management of localized prostate cancer is complicated because of cancer heterogeneity and differentiated progression in various subgroups of patients. As a prostate cancer biomarker, FDA-approved detection assay for serum prostate specific antigen (PSA) and its derivatives are not potent enough to diagnose prostate cancer, especially high-grade disease (Gleason ≥7). To date, a collection of ne...
Source: Seminars in Cancer Biology - March 17, 2018 Category: Cancer & Oncology Source Type: research

Histopathological growth patterns as a candidate biomarker for immunomodulatory therapy
Publication date: Available online 31 January 2018 Source:Seminars in Cancer Biology Author(s): Pieter-Jan van Dam, Sofie Daelemans, Elizabeth Ross, Yannick Waumans, Steven Van Laere, Emily Latacz, Roanne Van Steen, Christel De Pooter, Mark Kockx, Luc Dirix, Peter B. Vermeulen The encroachment of a growing tumor upon the cells and structures of surrounding normal tissue results in a series of histopathological growth patterns (HGPs). These morphological changes can be assessed in hematoxylin-and-eosin (H&E) stained tissue sections from primary and metastatic tumors and have been characterized in a range of tissue ...
Source: Seminars in Cancer Biology - March 17, 2018 Category: Cancer & Oncology Source Type: research

Primary and metastatic brain cancer genomics and emerging biomarkers for immunomodulatory cancer treatment
Publication date: Available online 31 January 2018 Source:Seminars in Cancer Biology Author(s): F. Passiglia, C. Caglevic, E. Giovannetti, JA. Pinto, P. Manca, S. Taverna, A. Listì, I. Gil-Bazo, LE. Raez, A. Russo, C. Rolfo Recent studies with immunomodulatory agents targeting both cytotoxic T-lymphocyte protein 4 (CTLA4) and programmed cell death 1 (PD1)/programmed cell death ligand 1 (PDL1) have shown to be very effective in several cancers revealing an unexpected great activity in patients with both primary and metastatic brain tumors. Combining anti-CTLA4 and anti-PD1 agents as upfront systemic therapy has reve...
Source: Seminars in Cancer Biology - March 17, 2018 Category: Cancer & Oncology Source Type: research

Head and neck squamous cell carcinoma: Genomics and emerging biomarkers for immunomodulatory cancer treatments
Publication date: Available online 31 January 2018 Source:Seminars in Cancer Biology Author(s): Benjamin Solomon, Richard J. Young, Danny Rischin Head and neck squamous cell carcinoma (HNSCC) comprises a heterogeneous group of tumors that arise from the squamous epithelium of the oral cavity, oropharynx, larynx and hypopharynx. While many HNSCCs are related to classical etiologic factors of smoking and alcohol, a clinically, genomically, and immunologically distinct subgroup of tumors arise from the epithelium of the tonsil and the base of tongue as a result of infection with Human Papilloma Virus (HPV). In this review we...
Source: Seminars in Cancer Biology - March 17, 2018 Category: Cancer & Oncology Source Type: research

AGC kinases in cancer metastasis, immune checkpoint regulation and drug resistance
Publication date: February 2018 Source:Seminars in Cancer Biology, Volume 48 Author(s): Gongda Xue, Brian A. Hemmings (Source: Seminars in Cancer Biology)
Source: Seminars in Cancer Biology - March 17, 2018 Category: Cancer & Oncology Source Type: research

Blocking Ras inhibition as an antitumor strategy
Publication date: Available online 2 February 2018 Source:Seminars in Cancer Biology Author(s): Nagore I. Marín-Ramos, Silvia Ortega-Gutiérrez, María L. López-Rodríguez Ras proteins are among the most frequently mutated drivers in human cancer and remain an elusive pharmaceutical targeting. Previous studies have improved the understanding of Ras structure, processing, and signaling pathways in cancer cells and have opened new possibilities for inhibiting Ras function. In this review we discuss the most recent advances towards inhibiting Ras activity with small molecules, highlighting the...
Source: Seminars in Cancer Biology - March 17, 2018 Category: Cancer & Oncology Source Type: research

Genetic status of KRAS influences Transforming Growth Factor-beta (TGF- β) signaling: An insight into Neuropilin-1 (NRP1) mediated tumorigenesis
Publication date: Available online 2 February 2018 Source:Seminars in Cancer Biology Author(s): Sneha Vivekanandhan, Debabrata Mukhopadhyay Oncogenic RAS and deregulated transforming growth factor-beta (TGF)-β signaling have been implicated in several cancers. So far, attempts to target either one of them therapeutically have been futile as both of them are involved in multiple fundamental cellular processes and the normal forms are expressed by almost all cells. Hence, their inhibition would disrupt several physiological processes. Besides, their downregulation stimulates the tumor cells to develop adaptive mechanis...
Source: Seminars in Cancer Biology - March 17, 2018 Category: Cancer & Oncology Source Type: research

FOXO family in regulating cancer and metabolism
Publication date: Available online 2 February 2018 Source:Seminars in Cancer Biology Author(s): Jian Ma, Smita Matkar, Xin He, Xianxin Hua FOXO proteins are a sub-group of a superfamily of forkhead box (FOX)-containing transcription factors (TFs). FOXOs play an important role in regulating a plethora of biological activities ranging from development, cell signaling, and tumorigenesis to cell metabolism. Here we mainly focus on reviewing the role of FOXOs in regulating tumor and metabolism. Moreover, how crosstalk among various pathways influences the function of FOXOs will be reviewed. Further, the paradoxical role for FO...
Source: Seminars in Cancer Biology - March 17, 2018 Category: Cancer & Oncology Source Type: research

Understanding the microbiome: Emerging biomarkers for exploiting the microbiota for personalized medicine against cancer
Publication date: Available online 6 February 2018 Source:Seminars in Cancer Biology Author(s): Meenakshi Rajpoot, Anil K. Sharma, Anil Sharma, Girish Kumar Gupta The human body is a home to more than 1 trillion microbes with a diverse variety of commensal microbes that play a crucial role towards the health of the individual. These microbes occupy different habitats such as gut, skin, vagina, oral etc. Not only the types and abundance of microbes are different in different organs, but also these may differ in different individuals. The genome of these microbiota and their ecosystem constitute to form a microbiome. Factor...
Source: Seminars in Cancer Biology - March 17, 2018 Category: Cancer & Oncology Source Type: research

Forkhead box O proteins: Crucial regulators of cancer EMT
Publication date: Available online 7 February 2018 Source:Seminars in Cancer Biology Author(s): Zhiqiang Ma, Zhenlong Xin, Wei Hu, Shuai Jiang, Zhi Yang, Xiaolong Yan, Xiaofei Li, Yang Yang, Fulin Chen The epithelial-mesenchymal transition (EMT) is an acknowledged cellular transition process in which epithelial cells acquire mesenchymal-like properties that endow cancer cells with increased migratory and invasive behavior. Forkhead box O (FOXO) proteins have been shown to orchestrate multiple EMT-associated pathways and EMT-related transcription factors (EMT-TFs), thereby modulating the EMT process. The focus of the curre...
Source: Seminars in Cancer Biology - March 17, 2018 Category: Cancer & Oncology Source Type: research

Epigenetic deregulation in chronic lymphocytic leukemia: Clinical and biological impact
Publication date: Available online 7 February 2018 Source:Seminars in Cancer Biology Author(s): Larry Mansouri, Justyna Anna Wierzbinska, Christoph Plass, Richard Rosenquist Deregulated transcriptional control caused by aberrant DNA methylation and/or histone modifications is a hallmark of cancer cells. In chronic lymphocytic leukemia (CLL), the most common adult leukemia, the epigenetic ‘landscape’ has added a new layer of complexity to our understanding of this clinically and biologically heterogeneous disease. Early studies identified aberrant DNA methylation, often based on single gene promoter analysis wi...
Source: Seminars in Cancer Biology - March 17, 2018 Category: Cancer & Oncology Source Type: research

Cancer Molecular Markers: A guide to cancer detection and Management.
Publication date: Available online 8 February 2018 Source:Seminars in Cancer Biology Author(s): Meera Nair, Sardul Singh Sandhu, Anil Kumar Sharma Cancer is generally caused by the molecular alterations which lead to specific mutations. Advances in molecular biology have provided an impetus to the study of cancers with valuable prognostic and predictive significance. Over the hindsight various attempts have been undertaken by scientists worldwide, in the management of cancer; where, we have witnessed a number of molecular markers which allow the early detection of cancers and lead to a decrease in its mortality rate. Rece...
Source: Seminars in Cancer Biology - March 17, 2018 Category: Cancer & Oncology Source Type: research

Immuno-oncology-101: overview of major concepts and translational perspectives
Publication date: Available online 8 February 2018 Source:Seminars in Cancer Biology Author(s): B. Allard, S. Aspeslagh, S. Garaud, F.A. Dupont, C. Solinas, M. Kok, B. Routy, C. Sotiriou, J. Stagg, L. Buisseret Cancer immunotherapy is demonstrating impressive clinical benefit in different malignancies and clinical oncologists are increasingly turning their attention to immune-oncology. It is now well recognized that innate and adaptive immune cells infiltrating tumors are associated with clinical outcomes and responses to treatments, and can be harnessed to patients’ benefit. Considerable advances have also been mad...
Source: Seminars in Cancer Biology - March 17, 2018 Category: Cancer & Oncology Source Type: research

New weapons to penetrate the armor: Novel reagents and assays developed at the NCI RAS Initiative to enable discovery of RAS therapeutics
Publication date: Available online 9 February 2018 Source:Seminars in Cancer Biology Author(s): Dominic Esposito, Andrew G. Stephen, Thomas J. Turbyville, Matthew Holderfield Development of therapeutic strategies against RAS-driven cancers has been challenging due in part to a lack of understanding of the biology of the system and the ability to design appropriate assays and reagents for targeted drug discovery efforts. Recent developments in the field have opened up new avenues for exploration both through advances in the number and quality of reagents as well as the introduction of novel biochemical and cell-based assay...
Source: Seminars in Cancer Biology - March 17, 2018 Category: Cancer & Oncology Source Type: research

Targeting the RAS-dependent chemoresistance: The Warburg connection
Publication date: Available online 9 February 2018 Source:Seminars in Cancer Biology Author(s): Roberto Serna-Blasco, Marta Sanz-Álvarez, Óscar Aguilera, Jesús García-Foncillas RAS protein family members (KRAS4A, KRAS4B, HRAS and NRAS) function as GDP–GTP-regulated on-off switches, which regulate cytoplasmic-nuclear signaling networks ruling diverse normal cellular processes. Constitutive activating mutations in RAS genes are found in up to 30% of human cancers, and remarkably, the oncogenic Ras mutations and mutations in other components of Ras/MAPK signaling pathways seem to be mutually...
Source: Seminars in Cancer Biology - March 17, 2018 Category: Cancer & Oncology Source Type: research

Targeting I κappaB kinases for cancer therapy
Publication date: Available online 24 February 2018 Source:Seminars in Cancer Biology Author(s): 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 metastas...
Source: Seminars in Cancer Biology - March 17, 2018 Category: Cancer & Oncology Source Type: research

Oncogenic KRas mobility in the membrane and signaling response
Publication date: Available online 27 February 2018 Source:Seminars in Cancer Biology Author(s): 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), signali...
Source: Seminars in Cancer Biology - March 17, 2018 Category: Cancer & Oncology Source Type: research

Genomics and emerging biomarkers for immunotherapy of colorectal cancer
Publication date: Available online 1 March 2018 Source:Seminars in Cancer Biology Author(s): 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-...
Source: Seminars in Cancer Biology - March 17, 2018 Category: Cancer & Oncology Source Type: research

New insights into RAS biology reinvigorate interest in mathematical modeling of RAS signaling
Publication date: Available online 5 March 2018 Source:Seminars in Cancer Biology Author(s): 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...
Source: Seminars in Cancer Biology - March 17, 2018 Category: Cancer & Oncology Source Type: research

RAS-mediated oncogenic signaling pathways in human malignancies
Publication date: Available online 7 March 2018 Source:Seminars in Cancer Biology Author(s): 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....
Source: Seminars in Cancer Biology - March 17, 2018 Category: Cancer & Oncology Source Type: research

FOXOs in Cancer Immunity: Knowns and Unknowns
Publication date: Available online 5 January 2018 Source:Seminars in Cancer Biology Author(s): Youcai Deng, Fangjie Wang, Tiffany Hughes, Jianhua Yu In the tumor microenvironment (TME), cancer cells, stromal cells, and immune cells, along with their extracellular factors, have profound effects on either promoting or repressing anti-cancer immunity. Accumulating evidence has shown the paradoxical intrinsic role of the Forkhead box O (FOXO) family of transcription factors in cancer, which can act as a tumor repressor while also maintaining cancer stem cells. FOXOs also regulate cancer immunity. FOXOs promote antitumor activ...
Source: Seminars in Cancer Biology - January 5, 2018 Category: Cancer & Oncology Source Type: research

A transatlantic perspective on the integration of Immuno-Oncology Prognostic and Predictive Biomarkers in innovative clinical trial design
Publication date: Available online 5 January 2018 Source:Seminars in Cancer Biology Author(s): M. Morfouace, S.M. Hewitt, R. Salgado, K. Hartmann, S. Litiere, S. Tejpar, V. Golfinopoulos, T. Lively, M. Thurin, B. Conley, D. Lacombe Immuno-therapeutics aim to activate the body’s own immune system against cancer and are one of the most promising cancer treatment strategies, but currently limited by a variable response rate. Biomarkers may help to distinguish those patients most likely to respond to therapy; they may also help guide clinical decision making for combination therapies, dosing schedules, and determining p...
Source: Seminars in Cancer Biology - January 5, 2018 Category: Cancer & Oncology Source Type: research

FoxO transcription factors in cancer metabolism
Publication date: Available online 5 January 2018 Source:Seminars in Cancer Biology Author(s): Raj Kumar Yadav, Anoop Singh Chauhan, Li Zhuang, Boyi Gan FoxO transcription factors serve as the central regulator of cellular homeostasis and are tumor suppressors in human cancers. Recent studies have revealed that, besides their classic functions in promoting cell death and inducing cell cycle arrest, FoxOs also regulate cancer metabolism, an emerging hallmark of cancer. In this review, we summarize the regulatory mechanisms employed to control FoxO activities in the context of cancer biology, and discuss FoxO function in me...
Source: Seminars in Cancer Biology - January 5, 2018 Category: Cancer & Oncology Source Type: research

Is Nanoclustering essential for all oncogenic KRas pathways? Can it explain why wild-type KRas can inhibit its oncogenic variant?
Publication date: Available online 5 January 2018 Source:Seminars in Cancer Biology Author(s): Ruth Nussinov, Chung-Jung Tsai, Hyunbum Jang Membrane-anchored oncogenic KRas can dimerize, form nanoclusters, and signal through the MAPK (Raf/MEK/ERK) and PI3Kα/Akt/mTOR. Both pathways are needed in KRAS-driven proliferation. Here we ask: Is oncogenic KRas nanoclustering (or dimerization) essential for all KRas signaling pathways? Raf kinase domain dimerization, thus MAPK activation, requires KRas nanoclusters. By contrast, the PI3Kα heterodimer acts as a monomeric unit; thus, does PI3Kα activation and PI3K&a...
Source: Seminars in Cancer Biology - January 5, 2018 Category: Cancer & Oncology Source Type: research

Glycogen Synthase Kinases: Moonlighting Proteins with Theranostic Potential in Cancer
Publication date: Available online 5 January 2018 Source:Seminars in Cancer Biology Author(s): Siddavaram Nagini, Josephraj Sophia, Rajakishore Mishra Glycogen synthase kinase-3 (GSK-3), a serine/threonine kinase is an archetypal multifunctional moonlighting protein involved in diverse cellular processes including metabolism, insulin signaling, proliferation, differentiation, apoptosis, neuronal function and embryonic development. The two known isoforms, GSK-3α and GSK-3β that undergo activation/inactivation by post-translational, site-specific phosphorylation incorporate a vast number of substrates in their re...
Source: Seminars in Cancer Biology - January 5, 2018 Category: Cancer & Oncology Source Type: research

Bioblockades join the assault on small G protein signalling
Publication date: Available online 4 January 2018 Source:Seminars in Cancer Biology Author(s): Helen R. Mott, Darerca Owen Inhibition of Ras signalling has been a goal almost since its central role in cell signalling and its deregulation in disease were discovered. Early attempts at inhibiting its post-translational modification using peptidomimetics were successful in cell culture but failed spectacularly in clinical trials, making industry wary of targeting this critical oncoprotein. Small molecule inhibition of the protein-protein interactions involving Ras has also been difficult due to the nature of the interaction i...
Source: Seminars in Cancer Biology - January 4, 2018 Category: Cancer & Oncology Source Type: research