| 1. |
- Agathangelidis, Andreas, et al.
(författare)
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High-Throughput immunogenetics for precision medicine in cancer
- 2022
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Ingår i: Seminars in Cancer Biology. - : Elsevier. - 1044-579X .- 1096-3650. ; 84, s. 80-88
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Tidskriftsartikel (refereegranskat)abstract
- Cancer is characterized by an extremely complex biological background, which hinders personalized therapeutic interventions. Precision medicine promises to overcome this obstacle through integrating information from different 'subsystems', including the host, the external environment, the tumor itself and the tumor microenvironment. Immunogenetics is an essential tool that allows dissecting both lymphoid cancer ontogeny at both a cell-intrinsic and a cell-extrinsic level, i.e. through characterizing micro-environmental interactions, with a view to precision medicine. This is particularly thanks to the introduction of powerful, high-throughput approaches i.e. next generation sequencing, which allow the comprehensive characterization of immune repertoires. Indeed, NGS immunogenetic analysis (Immune-seq) has emerged as key to both understanding cancer pathogenesis and improving the accuracy of clinical decision making in oncology. Immune-seq has applications in lymphoid malignancies, assisting in the diagnosis e.g. through differentiating from reactive conditions, as well as in disease monitoring through accurate assessment of minimal residual disease. Moreover, Immune-seq facilitates the study of T cell receptor clonal dynamics in critical clinical contexts, including transplantation as well as innovative immunotherapy for solid cancers. The clinical utility of Immune-seq represents the focus of the present contribution, where we highlight what can be achieved but also what must be addressed in order to maximally realize the promise of Immune-seq in precision medicine in cancer.
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| 2. |
- Berg, Tracy J, et al.
(författare)
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Radiotherapy-induced remodeling of the tumor microenvironment by stromal cells
- 2022
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Ingår i: Seminars in Cancer Biology. - : Elsevier BV. - 1096-3650 .- 1044-579X. ; 86:Part 3, s. 846-856
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Forskningsöversikt (refereegranskat)abstract
- Cancer cells reside amongst a complex milieu of stromal cells and structural features known as the tumor microenvironment. Often cancer cells divert and co-opt functions of stromal cells of the microenvironment to support tumor progression and treatment resistance. During therapy targeting cancer cells, the stromal cells of the microenvironment receive therapy to the same extent as cancer cells. Stromal cells therefore activate a variety of responses to the damage induced by these therapies, and some of those responses may support tumor progression and resistance. We review here the response of stromal cells to cancer therapy with a focus on radiotherapy in glioblastoma. We highlight the response of endothelial cells and the vasculature, macrophages and microglia, and astrocytes, as well as describing resulting changes in the extracellular matrix. We emphasize the complex interplay of these cellular factors in their dynamic responses. Finally, we discuss their resulting support of cancer cells in tumor progression and therapy resistance. Understanding the stromal cell response to therapy provides insight into complementary therapeutic targets to enhance tumor response to existing treatment options.
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| 3. |
- Cerezo-Magaña, M., et al.
(författare)
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The pleiotropic role of proteoglycans in extracellular vesicle mediated communication in the tumor microenvironment
- 2020
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Ingår i: Seminars in Cancer Biology. - : ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD. - 1044-579X .- 1096-3650. ; 62, s. 99-107
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Forskningsöversikt (refereegranskat)abstract
- Compartmental exchange between cells through extracellular vesicles (EVs), including exosomes and microvesicles, has emerged as a central mechanism that coordinates the complex communication between malignant and stromal cells during tumor initiation and evolution. Some of the most critical processes of EV-mediated communication, including EV biogenesis and EV uptake, can be mediated by heparan sulfate proteoglycans (HSPGs) that reside on the surface of producer and recipient cells as well as on EVs. With interestingly similar, HSPG-dependent, pathways as the ones exploited by some viruses, EVs may, in an evolutionary perspective, be viewed as endogenous counterparts of viral particles. Cancer cell-derived EVs exert their protumorigenic effects by direct interactions of biologically active surface molecules, by transfer of proteins and nucleic acids into recipient cells or by transfer of metabolites that can be utilized as an energy source by the recipient cell. Here, we discuss the pleiotropic role of the HSPG family in these different contexts of EV communication with a specific focus on tumor development. We propose EV-associated PGs as dynamic reservoirs and chaperones of signaling molecules with potential implications in ligand exchange between EVs and tumor target cells. The protumorigenic consequences of EV mediated communication through HSPG should motivate the development of therapeutic approaches targeting EV-HSPG interactions as a novel strategy in cancer treatment.
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| 4. |
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| 5. |
- He, Fei, et al.
(författare)
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Sex dimorphism in the tumor microenvironment : From bench to bedside and back
- 2022
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Ingår i: Seminars in Cancer Biology. - : Elsevier. - 1044-579X .- 1096-3650. ; 86:3, s. 166-179
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Forskningsöversikt (refereegranskat)abstract
- Cancer represents a significant cause of death and suffering in both the developed and developing countries. Key underlying issues in the mortality of cancer are delayed diagnosis and resistance to treatments. However, improvements in biomarkers represent one important step that can be taken for alleviating the suffering caused by malignancy. Precision-based medicine is promising for revolutionizing diagnostic and treatment strategies for cancer patients worldwide. Contemporary methods, including various omics and systems biology approaches, as well as advanced digital imaging and artificial intelligence, allow more accurate assessment of tumor characteristics at the patient level. As a result, treatment strategies can be specifically tailored and adapted for individual and/or groups of patients that carry certain tumor characteristics. This includes immunotherapy, which is based on characterization of the immunosuppressive tumor microenvironment (TME) and, more specifically, the presence and activity of immune cell subsets. Unfortunately, while it is increasingly clear that gender strongly affects immune regulation and response, there is a knowledge gap concerning differences in sex-specific immune responses and how these contribute to the immunosuppressive TME and the response to immunotherapy. In fact, sex dimorphism is poorly understood in cancer progression and is typically ignored in current clinical practice. In this review, we aim to survey the available literature and highlight the existing knowledge gap in order to encourage further studies that would contribute to understanding both gender-biased immunosuppression in the TME and the driver of tumor progression towards invasive and metastatic disease. The review highlights the need to include sex optimized/genderized medicine as a new concept in future medicine cancer diagnostics and treatments.
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| 6. |
- Hemminki, Kari, et al.
(författare)
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Autoimmune diseases and hematological malignancies : exploring the underlying mechanisms from epidemiological evidence
- 2020
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Ingår i: Seminars in Cancer Biology. - : Elsevier BV. - 1096-3650 .- 1044-579X. ; 64, s. 114-121
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Forskningsöversikt (refereegranskat)abstract
- Autoimmune diseases are characterized by the irregular functioning of the immune system that leads to the loss of tolerance to self-antigens. The underlying nature of autoimmune diseases has led to speculation that the risk of malignancy might be higher or lower in patients with such diseases. However, the rarity and heterogeneity of both autoimmune diseases and malignancies is the main challenge for systematic exploration of associations between autoimmune diseases and cancer. The nationwide usages of electronic health records in Sweden and other countries has created longitudinal clinical datasets of large populations, which are ideal for quantifying the associations as well as possible guidance concerning the underlying mechanisms. In this report, we firstly summarize the population-based epidemiological association studies between autoimmune diseases and subsequent hematological malignancies using data derived mainly from Swedish nationwide data. These include over one million cancer cases and approximately 500,000 patients with medically diagnosed autoimmune disease. We further discuss the underlying mechanisms that contribute to the observed association between autoimmune diseases and hematological malignancies, including shared genetics, environmental factors, medical treatments of autoimmune diseases as well as dysregulated immune function.
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| 7. |
- Kajitani, Naoko, et al.
(författare)
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The role of RNA-binding proteins in the processing of mRNAs produced by carcinogenic papillomaviruses
- 2022
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Ingår i: Seminars in Cancer Biology. - : Elsevier BV. - 1044-579X .- 1096-3650. ; 86, s. 482-496
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Forskningsöversikt (refereegranskat)abstract
- Human papillomaviruses (HPV) are epitheliotropic DNA tumor viruses that are prevalent in the human population. A subset of the HPVs termed high-risk HPVs (HR-HPVs) are causative agents of anogenital cancers and head-and-neck cancers. Cancer is the result of persistent high-risk HPV infections that have not been cleared by the immune system of the host. These infections are characterized by dysregulated HPV gene expression, in particular constitutive high expression of the HPV E6 and E7 oncogenes and absence of the highly immunogenic viral L1 and L2 capsid proteins. HPVs make extensive use of alternative mRNA splicing to express its genes and are therefore highly dependent on cellular RNA-binding proteins for proper gene expression. Levels of RNA-binding proteins are altered in HPV-containing premalignant cervical lesions and in cervical cancer. Here we review our current knowledge of RNA-binding proteins that control HPV gene expression. We focus on RNA-binding proteins that control expression of the E6 and E7 oncogenes since they initiate and drive development of cancer and on the immunogenic L1 and L2 proteins as there silencing may contribute to immune evasion during carcinogenesis. Furthermore, cellular RNA-binding proteins are essential for HPV gene expression and as such may be targets for therapy to HPV infections and HPV-driven cancers.
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| 8. |
- Lilljebjörn, Henrik, et al.
(författare)
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Transcriptomics paving the way for improved diagnostics and precision medicine of acute leukemia
- 2022
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Ingår i: Seminars in Cancer Biology. - : Elsevier BV. - 1044-579X. ; 84, s. 40-49
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Tidskriftsartikel (refereegranskat)abstract
- Transcriptional profiling of acute leukemia, specifically by RNA-sequencing or whole transcriptome sequencing (WTS), has provided fundamental insights into its underlying disease biology and allows unbiased detection of oncogenic gene fusions, as well as of gene expression signatures that can be used for improved disease classification. While used as a research tool for many years, RNA-sequencing is becoming increasingly used in clinical diagnostics. Here, we highlight key transcriptomic studies of acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) that have improved our biological understanding of these heterogeneous malignant disorders and have paved the way for translation into clinical diagnostics. Recent single-cell transcriptomic studies of ALL and AML, which provide new insights into the cellular ecosystem of acute leukemia and point to future clinical utility, are also reviewed. Finally, we discuss current challenges that need to be overcome for a more wide-spread adoption of RNA-sequencing in clinical diagnostics and how this technology significantly can aid the identification of genetic alterations in current guidelines and of newly emerging disease entities, some of which are critical to identify because of the availability of targeted therapies, thereby paving the way for improved precision medicine of acute leukemia.
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| 9. |
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| 10. |
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| 11. |
- Molnar-Gabor, Fruzsina, et al.
(författare)
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Harmonization after the GDPR? Divergences in the rules for genetic and health data sharing in four member states and ways to overcome them by EU measures: insights from Germany, Greece, Latvia and Sweden
- 2022
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Ingår i: Seminars in Cancer Biology. - : Elsevier. - 1044-579X .- 1096-3650. ; 84, s. 271-283
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Tidskriftsartikel (refereegranskat)abstract
- The EU member states’ healthcare and health-related research sectors are both characterized by an emerging infrastructural coalescence on a national and European level. The culmination of this coalescence is the planned creation of a European Health Data Space, an EU-wide infrastructure for the processing of personal data for healthcare and for secondary uses such as scientific research. In contrast to growing technical interoperability, the legal framework for such integration is not yet defined in detail, particularly with regard to data protection law. Its development is accompanied by discussions about divergent member state implementations of the EU General Data Protection Regulation (GDPR) that affect data sharing between healthcare and scientific research actors and across various sectors driven by divergent processing purposes.The article presents four member states’ main rules on data sharing based on the respective provision of the GDPR in six health-related contexts regarding data sharing across the healthcare and research sector and between the main actors of those sectors. The striking differences are then evaluated from the perspective of their factual effect on European data sharing depending on the legal characteristics of the GDPR provisions they rely on. Against this backdrop, the planned regulatory measures for the setup of the European Health Data Space are introduced and evaluated with regard to further harmonization between member states’ laws and possibilities to overcome divergences in data protection rules relevant for European data sharing.The results of the analysis point to the conclusion that the destructive effect of divergent member state rules depends on the legal qualification of the EU provisions they rely on and that this qualification also determines which further EU regulatory measure would be the most effective to set the framework for the European Health Data Space.
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| 12. |
- Nyström, Hanna, 1980-
(författare)
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Extracellular matrix proteins in metastases to the liver : Composition, function and potential applications
- 2021
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Ingår i: Seminars in Cancer Biology. - : Academic Press. - 1044-579X .- 1096-3650. ; 71, s. 134-142
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Tidskriftsartikel (refereegranskat)abstract
- The rising evidence of the tumor microenvironment (TME) and its role in cancer have made this an area of increased research efforts. The focus is both on the primary tumor but also on the metastatic setting. The TME though, does not only consist of the non-malignant cells of a tumor, but also of the acellular compartment: The Extracellular Matrix (ECM). The liver is a common organ for metastasis of many cancers and for some of these cancers' liver surgery is a standard treatment with long-term cure, whereas for other cancers not considered meaningful. Blood supply and anatomical reasons plays one part for the establishment of liver metastasis. It is however a well-known fact that the "soil" of a metastatic organ is of utter importance in the process of metastasis. The "soil" consists of the TME where the ECM is a critical and active part. This review focuses what is known about the normal ECM of the human liver, what is known about ECM proteins in human liver metastasis, challenges of studying the ECM in liver metastases and lastly, potential applications of this field of knowledge.
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| 13. |
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| 14. |
- Pienta, K. J., et al.
(författare)
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Cancer cells employ an evolutionarily conserved polyploidization program to resist therapy
- 2022
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Ingår i: Seminars in Cancer Biology. - : Elsevier BV. - 1044-579X. ; 81, s. 145-159
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Tidskriftsartikel (refereegranskat)abstract
- Unusually large cancer cells with abnormal nuclei have been documented in the cancer literature since 1858. For more than 100 years, they have been generally disregarded as irreversibly senescent or dying cells, too morphologically misshapen and chromatin too disorganized to be functional. Cell enlargement, accompanied by whole genome doubling or more, is observed across organisms, often associated with mitigation strategies against environmental change, severe stress, or the lack of nutrients. Our comparison of the mechanisms for polyploidization in other organisms and non-transformed tissues suggest that cancer cells draw from a conserved program for their survival, utilizing whole genome doubling and pausing proliferation to survive stress. These polyaneuploid cancer cells (PACCs) are the source of therapeutic resistance, responsible for cancer recurrence and, ultimately, cancer lethality.
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| 15. |
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| 16. |
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| 17. |
- Rosenquist, R, et al.
(författare)
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Precision medicine in cancer: A paradigm shift
- 2022
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Ingår i: Seminars in cancer biology. - : Elsevier BV. - 1096-3650 .- 1044-579X. ; 84, s. 1-2
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 18. |
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| 19. |
- Skandalis, Spyros S., et al.
(författare)
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Intracellular hyaluronan : Importance for cellular functions
- 2020
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Ingår i: Seminars in Cancer Biology. - : Elsevier. - 1044-579X .- 1096-3650. ; 62, s. 20-30
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Forskningsöversikt (refereegranskat)abstract
- Hyaluronan-rich matrices are abundant in ECM and are involved in biological processes, such as cell growth and migration. Hyaluronan is synthesized by the hyaluronan synthase family of enzymes, HAS1, HAS2 and HAS3; the HAS1 and HAS3 genes give rise to different transcripts through alternative splicing, and the HAS2 gene to a noncoding RNA antisense transcript in addition to the protein-coding transcript. Biosynthesis of hyaluronan increases during inflammation and cancer and is regulated by cytokines and growth factors. In addition to extracellular hyaluronan-rich matrices, cytoplasmic and nuclear forms of hyaluronan have been detected in normal and pathological processes. Extra- and infra-cellular hyaluronan binds to hyaluronan binding proteins, such as CD44, RHAMM, CDC37 and USP17, affecting cellular behavior. Although neither the exact mechanisms by which hyaluronan is present in the intracellular compartments, nor its function at these sites are currently understood, there are evidence that intracellular hyaluronan has important regulatory roles during cell cycle, cell motility, RNA translation and splicing, and autophagy.
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| 20. |
- Stenzinger, Albrecht, et al.
(författare)
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Trailblazing precision medicine in Europe : A joint view by Genomic Medicine Sweden and the Centers for Personalized Medicine, ZPM, in Germany
- 2022
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Ingår i: Seminars in Cancer Biology. - : Elsevier. - 1044-579X .- 1096-3650. ; 84, s. 242-254
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Tidskriftsartikel (refereegranskat)abstract
- Over the last decades, rapid technological and scientific advances have led to a merge of molecular sciences and clinical medicine, resulting in a better understanding of disease mechanisms and the development of novel therapies that exploit specific molecular lesions or profiles driving disease. Precision oncology is here used as an example, illustrating the potential of precision/personalized medicine that also holds great promise in other medical fields. Real-world implementation can only be achieved by dedicated healthcare connected centers which amass and build up interdisciplinary expertise reflecting the complexity of precision medicine. Networks of such centers are ideally suited for a nation-wide outreach offering access to precision medicine to patients independent of their place of residence. Two of these multicentric initiatives, Genomic Medicine Sweden (GMS) and the Centers for Personalized Medicine (ZPM) initiative in Germany have teamed up to present and share their views on core concepts, potentials, challenges, and future developments in precision medicine. Together with other initiatives worldwide, GMS and ZPM aim at providing a robust and sustainable framework, covering all components from technology development to clinical trials, ethical and legal aspects as well as involvement of all relevant stakeholders, including patients and policymakers in the field.
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| 21. |
- Tolmachev, Vladimir, et al.
(författare)
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The emerging role of radionuclide molecular imaging of HER2 expression in breast cancer
- 2021
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Ingår i: Seminars in Cancer Biology. - : Elsevier BV. - 1044-579X .- 1096-3650. ; 72, s. 185-197
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Forskningsöversikt (refereegranskat)abstract
- Targeting of human epidermal growth factor type 2 (HER2) using monoclonal antibodies, antibody-drug conjugates and tyrosine kinase inhibitors extends survival of patients with HER2-expressing metastatic breast cancer. High expression of HER2 is a predictive biomarker for such specific treatment. Accurate determination of HER2 expression level is necessary for stratification of patients to targeted therapy. Non-invasive in vivo radionuclide molecular imaging of HER2 has a potential of repetitive measurements, addressing issues of heterogeneous expression and conversion of HER2 status during disease progression or in response to therapy. Imaging probes based of several classes of targeting proteins are currently in preclinical and early clinical development. Both preclinical and clinical data suggest that the most promising are imaging agents based on small proteins, such as single domain antibodies or engineered scaffold proteins. These agents permit a very specific high-contrast imaging at the day of injection.
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| 22. |
- Turanli, Beste Calimlioglu, et al.
(författare)
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Systems biology based drug repositioning for development of cancer therapy
- 2021
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Ingår i: Seminars in Cancer Biology. - : Elsevier BV. - 1096-3650 .- 1044-579X. ; 68, s. 47-58
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Forskningsöversikt (refereegranskat)abstract
- Drug repositioning is a powerful method that can assists the conventional drug discovery process by using existing drugs for treatment of a disease rather than its original indication. The first examples of repurposed drugs were discovered serendipitously, however data accumulated by high-throughput screenings and advancements in computational biology methods have paved the way for rational drug repositioning methods. As chemotherapeutic agents have notorious side effects that significantly reduce quality of life, drug repositioning promises repurposed noncancer drugs with little or tolerable adverse effects for cancer patients. Here, we review current drug-related data types and databases including some examples of web-based drug repositioning tools. Next, we describe systems biology approaches to be used in drug repositioning for effective cancer therapy. Finally, we highlight examples of mostly repurposed drugs for cancer treatment and provide an overview of future expectations in the field for development of effective treatment strategies.
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| 23. |
- Watabe, Tetsuro, et al.
(författare)
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Roles of TGF-β signals in tumor microenvironment via regulation of the formation and plasticity of vascular system
- 2023
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Ingår i: Seminars in Cancer Biology. - 1044-579X. ; 92, s. 130-138
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Forskningsöversikt (refereegranskat)abstract
- Tumor cells evolve in tumor microenvironment composed of multiple cell types. Among these, endothelial cells (ECs) are the major players in tumor angiogenesis, which is a driver of tumor progression and metastasis. Increasing evidence suggests that ECs also contribute to tumor progression and metastasis as they modify their phenotypes to differentiate into mesenchymal cells through a process known as endothelial-mesenchymal transition (EndoMT). This plasticity of ECs is mediated by various cytokines, including transforming growth factor-β (TGF-β), and modulated by other stimuli depending on the cellular contexts. Recent lines of evidence have shown that EndoMT is involved in various steps of tumor progression, including tumor angiogenesis, intravasation and extravasation of cancer cells, formation of cancer-associated fibroblasts, and cancer therapy resistance. In this review, we summarize current updates on EndoMT, highlight the roles of EndoMT in tumor progression and metastasis, and underline targeting EndoMT as a potential therapeutic strategy.
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| 24. |
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