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Article: The Matrix Reloaded-The Role of the Extracellular Matrix in Cancer.

Raskov, Hans / Gaggar, Shruti / Tajik, Asma / Orhan, Adile / Gögenur, Ismail

2023 Volume 15, Issue 7

Abstract: As the core component of all organs, the extracellular matrix (ECM) is an interlocking macromolecular meshwork of proteins, glycoproteins, and proteoglycans that provides mechanical support to cells and tissues. In cancer, the ECM can be remodelled in ... ...

Abstract	As the core component of all organs, the extracellular matrix (ECM) is an interlocking macromolecular meshwork of proteins, glycoproteins, and proteoglycans that provides mechanical support to cells and tissues. In cancer, the ECM can be remodelled in response to environmental cues, and it controls a plethora of cellular functions, including metabolism, cell polarity, migration, and proliferation, to sustain and support oncogenesis. The biophysical and biochemical properties of the ECM, such as its structural arrangement and being a reservoir for bioactive molecules, control several intra- and intercellular signalling pathways and induce cytoskeletal changes that alter cell shapes, behaviour, and viability. Desmoplasia is a major component of solid tumours. The abnormal deposition and composition of the tumour matrix lead to biochemical and biomechanical alterations that determine disease development and resistance to treatment. This review summarises the complex roles of ECM in cancer and highlights the possible therapeutic targets and how to potentially remodel the dysregulated ECM in the future. Furthering our understanding of the ECM in cancer is important as the modification of the ECM will probably become an important tool in the characterisation of individual tumours and personalised treatment options.
Language	English
Publishing date	2023-03-30
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers15072057
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Article: Neutrophils and polymorphonuclear myeloid-derived suppressor cells: an emerging battleground in cancer therapy.

Raskov, Hans / Orhan, Adile / Gaggar, Shruti / Gögenur, Ismail

Oncogenesis

2022 Volume 11, Issue 1, Page(s) 22

Abstract: Neutrophils are central mediators of innate and adaptive immunity and first responders to tissue damage. Although vital to our health, their activation, function, and resolution are critical to preventing chronic inflammation that may contribute to ... ...

Abstract	Neutrophils are central mediators of innate and adaptive immunity and first responders to tissue damage. Although vital to our health, their activation, function, and resolution are critical to preventing chronic inflammation that may contribute to carcinogenesis. Cancers are associated with the expansion of the neutrophil compartment with an escalation in the number of polymorphonuclear myeloid-derived suppressor cells (PMN-MDSC) in the peripheral circulation and tumor microenvironment. Although phenotypically similar to classically activated neutrophils, PMN-MDSC is pathologically activated and immunosuppressive in nature. They dynamically interact with other cell populations and tissue components and convey resistance to anticancer therapies while accelerating disease progression and metastatic spread. Cancer-associated neutrophilia and tumor infiltration of neutrophils are significant markers of poor outcomes in many cancers. Recently, there has been significant progress in the identification of molecular markers of PMN-MDSC providing insights into the central role of PMN-MDSC in the local tumor microenvironment as well as the systemic immune response in cancer. Further advances in sequencing and proteomics techniques will improve our understanding of their diverse functionalities and the complex molecular mechanisms at play. Targeting PMN-MDSC is currently one of the major focus areas in cancer research and several signaling pathways representing possible treatment targets have been identified. Positive results from preclinical studies clearly justify the current investigation in drug development and thus novel therapeutic strategies are being evaluated in clinical trials. In this review, we discuss the involvement of PMN-MDSC in cancer initiation and progression and their potential as therapeutic targets and clinical biomarkers in different cancers.
Language	English
Publishing date	2022-05-03
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2674437-5
ISSN	2157-9024
ISSN	2157-9024
DOI	10.1038/s41389-022-00398-3
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Article ; Online: Metabolic switch in cancer - Survival of the fittest.

Raskov, Hans / Gaggar, Shruti / Tajik, Asma / Orhan, Adile / Gögenur, Ismail

European journal of cancer (Oxford, England : 1990)

2022 Volume 180, Page(s) 30–51

Abstract: Cell metabolism is characterised by the highly coordinated conversion of nutrients into energy and biomass. In solid cancers, hypoxia, nutrient deficiencies, and tumour vasculature are incompatible with accelerated anabolic growth and require a rewiring ... ...

Abstract	Cell metabolism is characterised by the highly coordinated conversion of nutrients into energy and biomass. In solid cancers, hypoxia, nutrient deficiencies, and tumour vasculature are incompatible with accelerated anabolic growth and require a rewiring of cancer cell metabolism. Driver gene mutations direct malignant cells away from oxidation to maximise energy production and biosynthesis while tumour-secreted factors degrade peripheral tissues to fuel disease progression and initiate metastasis. As it is vital to understand cancer cell metabolism and survival mechanisms, this review discusses the metabolic switch and current drug targets and clinical trials. In the future, metabolic markers may be included when phenotyping individual tumours to improve the therapeutic opportunities for personalised therapy.
MeSH term(s)	Humans ; Neoplasms/drug therapy ; Energy Metabolism ; Glycolysis ; Mutation
Language	English
Publishing date	2022-11-26
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	82061-1
ISSN	1879-0852 ; 0277-5379 ; 0959-8049 ; 0964-1947
ISSN (online)	1879-0852
ISSN	0277-5379 ; 0959-8049 ; 0964-1947
DOI	10.1016/j.ejca.2022.11.025
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Zs.A 456: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Checkpoint inhibitor responses can be regulated by the gut microbiota - A systematic review.

Zeriouh, Mariam / Raskov, Hans / Kvich, Lasse / Gögenur, Ismail / Bennedsen, Astrid Louise Bjørn

Neoplasia (New York, N.Y.)

2023 Volume 43, Page(s) 100923

Abstract: Background: Evidence suggests that the human gut microbiota modulates the treatment response of immune checkpoint inhibitors (ICI) in cancer. Thus, finding predictive biomarkers in the fecal gut microbiota of patients who are less likely to respond to ... ...

Abstract	Background: Evidence suggests that the human gut microbiota modulates the treatment response of immune checkpoint inhibitors (ICI) in cancer. Thus, finding predictive biomarkers in the fecal gut microbiota of patients who are less likely to respond to ICI would be valuable. This systematic review aimed to investigate the association between fecal gut microbiota composition and ICI-treatment response in patients with cancer. Methods: EMBASE, Medline, and Cochrane Library databases were searched using the "Participants, Interventions, Comparisons, and Outcomes" (PICO) process to locate studies including participants with solid cancers treated with ICI intervention. The comparator was the gut microbiota, and the outcomes were oncological outcomes such as response rates and progression-free survival. Study data were synthesized qualitatively in a systematic narrative synthesis, and the risk of bias in the studies was assessed. Results: Two reviewers screened 2092 abstracts independently, and 140 studies were read as full-text reports and assessed for eligibility. Eighteen studies were included with 775 patients with different types of solid cancers who received anti-PD-1, anti-PD-L1, or anti-CTLA-4 therapy. Distinct patterns were observed in the patients' fecal samples. Some bacterial species were reported to be present in responders and non-responders, while others were present only in one group. The most reported species associated with better prognosis were Faecalibacterium prausnitzii, Streptococcus parasanguinis, Bacteroides caccae, and Prevotella copri. In contrast, the most reported species associated with poor prognosis were Blautia obeum and Bacteroides ovatus. Conclusion: Distinct microbiota features were associated with good and poor prognoses in ICI-treated patients with cancer.
MeSH term(s)	Humans ; Gastrointestinal Microbiome ; Microbiota ; Databases, Factual
Language	English
Publishing date	2023-08-19
Publishing country	United States
Document type	Systematic Review ; Journal Article ; Review
ZDB-ID	1483840-0
ISSN	1476-5586 ; 1522-8002
ISSN (online)	1476-5586
ISSN	1522-8002
DOI	10.1016/j.neo.2023.100923
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Zs.A 5203: Show issues

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Article: Cancer-Associated Fibroblasts and Tumor-Associated Macrophages in Cancer and Cancer Immunotherapy.

Raskov, Hans / Orhan, Adile / Gaggar, Shruti / Gögenur, Ismail

Frontiers in oncology

2021 Volume 11, Page(s) 668731

Abstract: Our understanding of the tumor microenvironment (TME), including the interplay between tumor cells, stromal cells, immune cells, and extracellular matrix components, is mandatory for the innovation of new therapeutic approaches in cancer. The cell-cell ... ...

Abstract	Our understanding of the tumor microenvironment (TME), including the interplay between tumor cells, stromal cells, immune cells, and extracellular matrix components, is mandatory for the innovation of new therapeutic approaches in cancer. The cell-cell communication within the TME plays a pivotal role in the evolution and progression of cancer. Cancer-associated fibroblasts (CAF) and tumor-associated macrophages (TAM) are major cell populations in the stroma of all solid tumors and often exert protumorigenic functions; however, the origin and precise functions of CAF and TAM are still incompletely understood. CAF and TAM hold significant potential as therapeutic targets to improve outcomes in oncology when combined with existing therapies. The regulation of CAF/TAM communication and/or their differentiation could be of high impact for improving the future targeted treatment strategies. Nevertheless, there is much scope for research and innovation in this field with regards to the development of novel drugs. In this review, we elaborate on the current knowledge on CAF and TAM in cancer and cancer immunotherapy. Additionally, by focusing on their heterogenous functions in different stages and types of cancer, we explore their role as potential therapeutic targets and highlight certain aspects of their functions that need further research.
Language	English
Publishing date	2021-05-20
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2649216-7
ISSN	2234-943X
ISSN	2234-943X
DOI	10.3389/fonc.2021.668731
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Article ; Online: Premetastatic niches, exosomes and circulating tumor cells: Early mechanisms of tumor dissemination and the relation to surgery.

Raskov, Hans / Orhan, Adile / Salanti, Ali / Gögenur, Ismail

International journal of cancer

2020 Volume 146, Issue 12, Page(s) 3244–3255

Abstract: The physiological stress response to surgery promotes wound healing and functional recovery and includes the activation of neural, inflammatory and proangiogenic signaling pathways. Paradoxically, the same pathways also promote metastatic spread and ... ...

Abstract	The physiological stress response to surgery promotes wound healing and functional recovery and includes the activation of neural, inflammatory and proangiogenic signaling pathways. Paradoxically, the same pathways also promote metastatic spread and growth of residual cancer. Human and animal studies show that cancer surgery can increase survival, migration and proliferation of residual tumor cells. To secure the survival and growth of disseminated tumor cells, the formation of premetastatic niches in target organs involves a complex interplay between microenvironment, immune system, circulating tumor cells, as well as chemical mediators and exosomes secreted by the primary tumor. This review describes the current understanding of the early mechanisms of dissemination, as well as how surgery may facilitate disease progression.
MeSH term(s)	Animals ; Cell Proliferation ; Cell Survival ; Disease Models, Animal ; Exosomes/immunology ; Exosomes/pathology ; Humans ; Neoplasm Seeding ; Neoplasm, Residual/blood ; Neoplasm, Residual/pathology ; Neoplasms/blood ; Neoplasms/pathology ; Neoplasms/prevention & control ; Neoplasms/surgery ; Neoplastic Cells, Circulating/immunology ; Neoplastic Cells, Circulating/pathology ; Neoplastic Stem Cells/immunology ; Neoplastic Stem Cells/pathology ; Surgical Procedures, Operative/adverse effects ; Tumor Microenvironment/immunology
Language	English
Publishing date	2020-01-03
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	218257-9
ISSN	1097-0215 ; 0020-7136
ISSN (online)	1097-0215
ISSN	0020-7136
DOI	10.1002/ijc.32820
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Zs.A 478: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 576: Show issues

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Article ; Online: Natural Killer Cells in Cancer and Cancer Immunotherapy.

Raskov, Hans / Orhan, Adile / Salanti, Ali / Gaggar, Shruti / Gögenur, Ismail

Cancer letters

2021 Volume 520, Page(s) 233–242

Abstract: The detection and killing of neoplastic cells require coordination of a variety of antitumor effector cells. Natural killer (NK) cells of the innate immune system are at the forefront of the body's defense systems and evidence suggests that the ... ...

Abstract	The detection and killing of neoplastic cells require coordination of a variety of antitumor effector cells. Natural killer (NK) cells of the innate immune system are at the forefront of the body's defense systems and evidence suggests that the infiltration and cytotoxicity of NK cells in the cancer tissue influence treatment efficacy and survival. As powerful effectors in the anticancer immune response, NK cells rapidly recognize and kill transformed cells with little reactivity against healthy self-tissues, which highlights their potential role in cancer immunotherapy. Modern immunotherapeutic approaches include immune checkpoint inhibitors to revitalize dysfunctional T cells and adoptive cell transfer using CD8
MeSH term(s)	CD8-Positive T-Lymphocytes/immunology ; Humans ; Immunotherapy ; Immunotherapy, Adoptive/trends ; Killer Cells, Natural/immunology ; Neoplasms/genetics ; Neoplasms/immunology ; Neoplasms/therapy ; Receptors, Chimeric Antigen/genetics ; Receptors, Chimeric Antigen/immunology ; Receptors, Chimeric Antigen/therapeutic use
Chemical Substances	Receptors, Chimeric Antigen
Language	English
Publishing date	2021-07-22
Publishing country	Ireland
Document type	Journal Article ; Review
ZDB-ID	195674-7
ISSN	1872-7980 ; 0304-3835
ISSN (online)	1872-7980
ISSN	0304-3835
DOI	10.1016/j.canlet.2021.07.032
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Zs.A 1177: Show issues

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Article: Electroporation and Immunotherapy-Unleashing the Abscopal Effect.

Justesen, Tobias Freyberg / Orhan, Adile / Raskov, Hans / Nolsoe, Christian / Gögenur, Ismail

Cancers

2022 Volume 14, Issue 12

Abstract: The discovery of electroporation in 1968 has led to the development of electrochemotherapy (ECT) and irreversible electroporation (IRE). ECT and IRE have been established as treatments of cutaneous and subcutaneous tumors and locally advanced pancreatic ... ...

Abstract	The discovery of electroporation in 1968 has led to the development of electrochemotherapy (ECT) and irreversible electroporation (IRE). ECT and IRE have been established as treatments of cutaneous and subcutaneous tumors and locally advanced pancreatic cancer, respectively. Interestingly, the treatment modalities have been shown to elicit immunogenic cell death, which in turn can induce an immune response towards the tumor cells. With the dawn of the immunotherapy era, the potential of combining ECT and IRE with immunotherapy has led to the launch of numerous studies. Data from the first clinical trials are promising, and new combination regimes might change the way we treat tumors characterized by low immunogenicity and high levels of immunosuppression, such as melanoma and pancreatic cancer. In this review we will give an introduction to ECT and IRE and discuss the impact on the immune system. Additionally, we will present the results of clinical and preclinical trials, investigating the combination of electroporation modalities and immunotherapy.
Language	English
Publishing date	2022-06-10
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers14122876
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Article ; Online: The gut microbiota can orchestrate the signaling pathways in colorectal cancer.

Bennedsen, Astrid L B / Furbo, Sara / Bjarnsholt, Thomas / Raskov, Hans / Gögenur, Ismail / Kvich, Lasse

APMIS : acta pathologica, microbiologica, et immunologica Scandinavica

2022 Volume 130, Issue 3, Page(s) 121–139

Abstract: Current evidence suggests that bacteria contribute to the development of certain cancers, such as colorectal cancer (CRC), partly by stimulating chronic inflammation. However, little is known about the bacterial impact on molecular pathways in CRC. ... ...

Abstract	Current evidence suggests that bacteria contribute to the development of certain cancers, such as colorectal cancer (CRC), partly by stimulating chronic inflammation. However, little is known about the bacterial impact on molecular pathways in CRC. Recent studies have demonstrated how specific bacteria can influence the major CRC-related pathways, i.e., Wnt, PI3K-Akt, MAPK, TGF-β, EGFR, mTOR, and p53. In order to advance the current understanding and facilitate the choice of pathways to investigate, we have systematically collected and summarized the current knowledge within bacterial altered major pathways in CRC. Several pro-tumorigenic and anti-tumorigenic bacterial species and their respective metabolites interfere with the major signaling pathways addressed in this review. Not surprisingly, some of these studies investigated known CRC drivers, such as Escherichia coli, Fusobacterium nucleatum, and Bacteroides fragilis. Interestingly, some metabolites produced by bacterial species typically considered pathogenic, e.g., Vibrio cholera, displayed anti-tumorigenic activities, emphasizing the caution needed when classifying healthy and unhealthy microorganisms. The results collectively emphasize the complexity of the relationship between the microbiota and the tumorigenesis of CRC, and future studies should verify these findings in more realistic models, such as organoids, which constitute a promising platform. Moreover, future trials should investigate the clinical potential of preventive modulation of the gut microbiota regarding CRC development.
MeSH term(s)	Animals ; Carcinogenesis/metabolism ; Colorectal Neoplasms/metabolism ; Colorectal Neoplasms/microbiology ; Gastrointestinal Microbiome/physiology ; Humans ; Signal Transduction/physiology
Language	English
Publishing date	2022-01-23
Publishing country	Denmark
Document type	Journal Article ; Review
ZDB-ID	93340-5
ISSN	1600-0463 ; 0903-4641
ISSN (online)	1600-0463
ISSN	0903-4641
DOI	10.1111/apm.13206
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Ud II Zs.73: Show issues

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Article ; Online: Cancer-Associated Fibroblasts and Tumor-Associated Macrophages in Cancer and Cancer Immunotherapy

Hans Raskov / Adile Orhan / Shruti Gaggar / Ismail Gögenur

Frontiers in Oncology, Vol

2021 Volume 11

Abstract	Our understanding of the tumor microenvironment (TME), including the interplay between tumor cells, stromal cells, immune cells, and extracellular matrix components, is mandatory for the innovation of new therapeutic approaches in cancer. The cell-cell communication within the TME plays a pivotal role in the evolution and progression of cancer. Cancer-associated fibroblasts (CAF) and tumor-associated macrophages (TAM) are major cell populations in the stroma of all solid tumors and often exert protumorigenic functions; however, the origin and precise functions of CAF and TAM are still incompletely understood. CAF and TAM hold significant potential as therapeutic targets to improve outcomes in oncology when combined with existing therapies. The regulation of CAF/TAM communication and/or their differentiation could be of high impact for improving the future targeted treatment strategies. Nevertheless, there is much scope for research and innovation in this field with regards to the development of novel drugs. In this review, we elaborate on the current knowledge on CAF and TAM in cancer and cancer immunotherapy. Additionally, by focusing on their heterogenous functions in different stages and types of cancer, we explore their role as potential therapeutic targets and highlight certain aspects of their functions that need further research.
Keywords	cancer-associated fibroblasts ; tumor-associated macrophages ; tumor microenvironment ; cancer immunotherapy ; cancer biology ; Neoplasms. Tumors. Oncology. Including cancer and carcinogens ; RC254-282
Subject code	610
Language	English
Publishing date	2021-05-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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