Gut Microbiota in Colorectal Cancer: Associations, Mechanisms, and Clinical Approaches

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Cayetano Pleguezuelos-Manzano ◽  
Jens Puschhof ◽  
Hans Clevers
Keyword(s):  
Colorectal Cancer ◽  
Escherichia Coli ◽  
Gut Microbiota ◽  
Cancer Biology ◽  
Fusobacterium Nucleatum ◽  
Annual Review ◽  
Publication Date ◽  
Experimental Systems ◽  
Induce Mutagenesis ◽  
Active Contribution

Colorectal cancer (CRC) is associated with the presence of particular gut microbes, as observed in many metagenomic studies to date. However, in most cases, it remains difficult to disentangle their active contribution to CRC from just a bystander role. This review focuses on the mechanisms described to date by which the CRC-associated microbiota could contribute to CRC. Bacteria like pks+ Escherichia coli, Fusobacterium nucleatum, or enterotoxigenic Bacteroides fragilis have been shown to induce mutagenesis, alter host epithelial signaling pathways, or reshape the tumor immune landscape in several experimental systems. The mechanistic roles of other bacteria, as well as newly identified fungi and viruses that are enriched in CRC, are only starting to be elucidated. Additionally, novel systems like organoids and organs-on-a-chip are emerging as powerful tools to study the direct effect of gut microbiota on healthy or tumor intestinal epithelium. Thus, the expanding knowledge of tumor-microbiota interactions holds promise for improved diagnosis and treatment of CRC. Expected final online publication date for the Annual Review of Cancer Biology, Volume 6 is April 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Bacterial Multicellularity: The Biology of Escherichia coli Building Large-Scale Biofilm Communities

2021 ◽  
Vol 75 (1) ◽  
Author(s):  
Diego O. Serra ◽  
Regine Hengge
Keyword(s):  
Escherichia Coli ◽  
Large Scale ◽  
Second Messengers ◽  
Emergent Properties ◽  
Annual Review ◽  
Publication Date ◽  
Growth And Survival ◽  
Chemical Gradients ◽  
Life Itself ◽  
Scale Matrix

Biofilms are a widespread multicellular form of bacterial life. The spatial structure and emergent properties of these communities depend on a polymeric extracellular matrix architecture that is orders of magnitude larger than the cells that build it. Using as a model the wrinkly macrocolony biofilms of Escherichia coli, which contain amyloid curli fibers and phosphoethanolamine (pEtN)-modified cellulose as matrix components, we summarize here the structure, building, and function of this large-scale matrix architecture. Based on different sigma and other transcription factors as well as second messengers, the underlying regulatory network reflects the fundamental trade-off between growth and survival. It controls matrix production spatially in response to long-range chemical gradients, but it also generates distinct patterns of short-range matrix heterogeneity that are crucial for tissue-like elasticity and macroscopic morphogenesis. Overall, these biofilms confer protection and a potential for homeostasis, thereby reducing maintenance energy, which makes multicellularity an emergent property of life itself. Expected final online publication date for the Annual Review of Microbiology, Volume 75 is October 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Central Role of the Antigen-Presentation and Interferon-γ Pathways in Resistance to Immune Checkpoint Blockade

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Annette Paschen ◽  
Ignacio Melero ◽  
Antoni Ribas
Keyword(s):  
Antigen Presentation ◽  
Tumor Cells ◽  
Mhc Class I ◽  
Cancer Biology ◽  
Interleukin 2 ◽  
Interferon Γ ◽  
Class I ◽  
Annual Review ◽  
Publication Date ◽  
Type I

Resistance to immunotherapy is due in some instances to the acquired stealth mechanisms of tumor cells that lose expression of MHC class I antigen–presenting molecules or downregulate their class I antigen–presentation pathways. Most dramatically, biallelic β2-microglobulin (B2M) loss leads to complete loss of MHC class I expression and to invisibility to CD8+ T cells. MHC class I expression and antigen presentation are potently upregulated by interferon-γ (IFNγ) in a manner that depends on IFNγ receptor (IFNGR) signaling via JAK1 and JAK2. Mutations in these molecules lead to IFNγ unresponsiveness and mediate loss of recognition and killing by cytotoxic T lymphocytes. Loss of MHC class I augments sensitivity of tumor cells to be killed by natural killer (NK) lymphocytes, and this mechanism could be exploited to revert resistance, for instance, with interleukin-2 (IL-2)-based agents. Moreover, in some experimental models, potent local type I interferon responses, such as those following intratumoral injection of Toll-like receptor 9 (TLR9) or TLR3 agonists, revert resistance due to mutations of JAKs. Expected final online publication date for the Annual Review of Cancer Biology, Volume 6 is April 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

TGFβ: Signaling Blockade for Cancer Immunotherapy

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Szu-Ying Chen ◽  
Ons Mamäi ◽  
Rosemary J. Akhurst
Keyword(s):  
Cancer Biology ◽  
Transforming Growth Factor ◽  
Biological Activities ◽  
Tumor Stroma ◽  
Transforming Growth Factor Β ◽  
Therapeutic Window ◽  
Annual Review ◽  
Publication Date ◽  
Tgfβ Signaling ◽  
Mesenchymal Transformation

Discovered over four decades ago, transforming growth factor β (TGFβ) is a potent pleiotropic cytokine that has context-dependent effects on most cell types. It acts as a tumor suppressor in some cancers and/or supports tumor progression and metastasis through its effects on the tumor stroma and immune microenvironment. In TGFβ-responsive tumors it can promote invasion and metastasis through epithelial-mesenchymal transformation, the appearance of cancer stem cell features, and resistance to many drug classes, including checkpoint blockade immunotherapies. Here we consider the biological activities of TGFβ action on different cells of relevance toward improving immunotherapy outcomes for patients, with a focus on the adaptive immune system. We discuss recent advances in the development of drugs that target the TGFβ signaling pathway in a tumor-specific or cell type–specific manner to improve the therapeutic window between response rates and adverse effects. Expected final online publication date for the Annual Review of Cancer Biology, Volume 6 is April 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Targeting KRAS G12C with Covalent Inhibitors

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Jonathan M.L. Ostrem ◽  
Kevan M. Shokat
Keyword(s):  
Clinical Trials ◽  
Cancer Biology ◽  
Phase Iii ◽  
Annual Review ◽  
Publication Date ◽  
Kras Mutations ◽  
Phase Iii Clinical Trials ◽  
Covalent Inhibitors ◽  
Novel Approaches ◽  
Early Phase Clinical Trials

KRAS is the most frequently mutated oncogene in cancer. Following numerous attempts to inhibit KRAS spanning multiple decades, recent efforts aimed at covalently targeting the mutant cysteine of KRAS G12C have yielded very encouraging results. Indeed, one such molecule, sotorasib, has already received accelerated US Food and Drug Administration approval with phase III clinical trials currently underway. A second molecule, adagrasib, has also progressed to phase III, and several others have entered early-phase clinical trials. The success of these efforts has inspired an array of novel approaches targeting KRAS, with some reporting extension to the two most common oncogenic KRAS mutations, G12V and G12D. Expected final online publication date for the Annual Review of Cancer Biology, Volume 6 is April 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

The Coevolution of Placentation and Cancer

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Günter P. Wagner ◽  
Kshitiz ◽  
Anasuya Dighe ◽  
Andre Levchenko
Keyword(s):  
Twentieth Century ◽  
Cancer Cells ◽  
Immune Evasion ◽  
Online Publication ◽  
Cancer Biology ◽  
Annual Review ◽  
Publication Date ◽  
Trophoblast Cells ◽  
Cancer Hallmarks ◽  
Placental Invasion

Analogies between placentation, in particular the behavior of trophoblast cells, and cancer have been noted since the beginning of the twentieth century. To what degree these can be explained as a consequence of the evolution of placentation has been unclear. In this review, we conclude that many similarities between trophoblast and cancer cells are shared with other, phylogenetically older processes than placentation. The best candidates for cancer hallmarks that can be explained by the evolution of eutherian placenta are mechanisms of immune evasion. Another dimension of the maternal accommodation of the placenta with an impact on cancer malignancy is the evolution of endometrial invasibility. Species with lower degrees of placental invasion tend to have lower vulnerability to cancer malignancy. We finally identify several areas in which one could expect to see coevolutionary changes in placental and cancer biology but that, to our knowledge, have not been explored. Expected final online publication date for the Annual Review of Animal Biosciences, Volume 10 is February 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

scholarly journals The Intestinal Microbiota and Colorectal Cancer

2020 ◽  
Vol 11 ◽  
Author(s):  
Yiwen Cheng ◽  
Zongxin Ling ◽  
Lanjuan Li
Keyword(s):  
Oxidative Stress ◽  
Colorectal Cancer ◽  
Escherichia Coli ◽  
Intestinal Microbiota ◽  
Pathogenic Bacteria ◽  
Large Population ◽  
Fusobacterium Nucleatum ◽  
Colorectal Carcinogenesis ◽  
Complex Relationship ◽  
Streptococcus Bovis

The intestinal microbiota, composed of a large population of microorganisms, is often considered a “forgotten organ” in human health and diseases. Increasing evidence indicates that dysbiosis of the intestinal microbiota is closely related to colorectal cancer (CRC). The roles for intestinal microorganisms that initiated and facilitated the CRC process are becoming increasingly clear. Hypothesis models have been proposed to illustrate the complex relationship between the intestinal microbiota and CRC. Recent studies have identified Streptococcus bovis, enterotoxigenic Bacteroides fragilis, Fusobacterium nucleatum, Enterococcus faecalis, Escherichia coli, and Peptostreptococcus anaerobius as CRC candidate pathogens. In this review, we summarized the mechanisms involved in microbiota-related colorectal carcinogenesis, including inflammation, pathogenic bacteria, and their virulence factors, genotoxins, oxidative stress, bacterial metabolites, and biofilm. We also described the clinical values of intestinal microbiota and novel strategies for preventing and treating CRC.

scholarly journals Reeling in the Zebrafish Cancer Models

2020 ◽  
Vol 5 (1) ◽  
Author(s):  
Alicia M. McConnell ◽  
Haley R. Noonan ◽  
Leonard I. Zon
Keyword(s):  
Cancer Biology ◽  
Model Organism ◽  
Transgenic Animals ◽  
Annual Review ◽  
Transgenic Zebrafish ◽  
Publication Date ◽  
Cancer Therapies ◽  
Cancer Models ◽  
Cancer Types ◽  
New Cancer Therapies

Zebrafish are rapidly becoming a leading model organism for cancer research. The genetic pathways driving cancer are highly conserved between zebrafish and humans, and the ability to easily manipulate the zebrafish genome to rapidly generate transgenic animals makes zebrafish an excellent model organism. Transgenic zebrafish containing complex, patient-relevant genotypes have been used to model many cancer types. Here we present a comprehensive review of transgenic zebrafish cancer models as a resource to the field and highlight important areas of cancer biology that have yet to be studied in the fish. The ability to image cancer cells and niche biology in an endogenous tumor make zebrafish an indispensable model organism in which we can further understand the mechanisms that drive tumorigenesis and screen for potential new cancer therapies. Expected final online publication date for the Annual Review of Cancer Biology, Volume 5 is March 4, 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

scholarly journals Framework and Strategies to Eliminate Disparities in Colorectal Cancer Screening Outcomes

2020 ◽  
Vol 72 (1) ◽  
Author(s):  
Chyke A. Doubeni ◽  
Kevin Selby ◽  
Samir Gupta
Keyword(s):  
Colorectal Cancer ◽  
Community Engagement ◽  
Health Equity ◽  
Screening Tests ◽  
Annual Review ◽  
Publication Date ◽  
Structural Barriers ◽  
Screening Process ◽  
Crc Screening ◽  
Racial Ethnic

Preventable differences in colorectal cancer (CRC) mortality across racial/ethnic, economic, geographic, and other groups can be eliminated by assuring equitable access and quality across the care continuum, but few interventions have been demonstrated to do so. Multicomponent strategies designed with a health equity framework may be effective. A health equity framework takes into account social determinants of health, multilevel influences (policy, community, delivery, and individual levels), screening processes, and community engagement. Effective strategies for increasing screening uptake include patient navigation and other interventions for structural barriers, reminders and clinical decision support, and data to continuously track metrics and guide targets for improvement. Community resource gaps should be addressed to assure high-quality services irrespective of racial/ethnic and socioeconomic status. One model combines population-based proactive outreach screening with delivery screening at in-person or virtual points of contact, as well as community engagement. Patient- and provider-based behavioral interventions may be considered for increasing screening demand and delivery. Providing a choice of screening tests is recommended for CRC screening, and access to colonoscopy is required for completion of the CRC screening process. Expected final online publication date for the Annual Review of Medicine, Volume 72 is January 27, 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

scholarly journals Nutritional Preconditioning in Cancer Treatment in Relation to DNA Damage and Aging

2020 ◽  
Vol 5 (1) ◽  
Author(s):  
Winnie M.C. van den Boogaard ◽  
Marry M. van den Heuvel-Eibrink ◽  
Jan H.J. Hoeijmakers ◽  
Wilbert P. Vermeij
Keyword(s):  
Dna Damage ◽  
Cancer Treatment ◽  
Cancer Biology ◽  
Accelerated Aging ◽  
Nutritional Intervention ◽  
Annual Review ◽  
Publication Date ◽  
Short And Long Term ◽  
Resilience Mechanisms

Dietary restriction (DR) is the most successful nutritional intervention for extending life span and preserving health in numerous species. Reducing food intake triggers a protective response that shifts energy resources from growth to maintenance and resilience mechanisms. This so-called survival response has been shown to particularly increase life and health span and decrease DNA damage in DNA repair–deficient mice exhibiting accelerated aging. Accumulation of DNA damage is the main cause of aging, but also of cancer. Moreover, radiotherapies and most chemotherapies are based on damaging DNA, consistent with their ability to induce toxicity and accelerate aging. Since fasting and DR decrease DNA damage and its effects, nutritional preconditioning holds promise for improving (cancer) therapy and preventing short- and long-term side effects of anticancer treatments. This review provides an overview of the link between aging and cancer, highlights important preclinical studies applying such nutritional preconditioning, and summarizes the first clinical trials implementing nutritional preconditioning in cancer treatment. Expected final online publication date for the Annual Review of Cancer Biology, Volume 5 is March 4, 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

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