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Immunity Oct 2023The cancer-immunity cycle provides a framework to understand the series of events that generate anti-cancer immune responses. It emphasizes the iterative nature of the... (Review)
Review
The cancer-immunity cycle provides a framework to understand the series of events that generate anti-cancer immune responses. It emphasizes the iterative nature of the response where the killing of tumor cells by T cells initiates subsequent rounds of antigen presentation and T cell stimulation, maintaining active immunity and adapting it to tumor evolution. Any step of the cycle can become rate-limiting, rendering the immune system unable to control tumor growth. Here, we update the cancer-immunity cycle based on the remarkable progress of the past decade. Understanding the mechanism of checkpoint inhibition has evolved, as has our view of dendritic cells in sustaining anti-tumor immunity. We additionally account for the role of the tumor microenvironment in facilitating, not just suppressing, the anti-cancer response, and discuss the importance of considering a tumor's immunological phenotype, the "immunotype". While these new insights add some complexity to the cycle, they also provide new targets for research and therapeutic intervention.
Topics: Humans; Immunotherapy; Neoplasms; T-Lymphocytes; Antigen Presentation; Genotype; Tumor Microenvironment
PubMed: 37820582
DOI: 10.1016/j.immuni.2023.09.011 -
CA: a Cancer Journal For Clinicians 2023Cancer development is driven by the accumulation of alterations affecting the structure and function of the genome. Whereas genetic changes disrupt the DNA sequence,... (Review)
Review
Cancer development is driven by the accumulation of alterations affecting the structure and function of the genome. Whereas genetic changes disrupt the DNA sequence, epigenetic alterations contribute to the acquisition of hallmark tumor capabilities by regulating gene expression programs that promote tumorigenesis. Shifts in DNA methylation and histone mark patterns, the two main epigenetic modifications, orchestrate tumor progression and metastasis. These cancer-specific events have been exploited as useful tools for diagnosis, monitoring, and treatment choice to aid clinical decision making. Moreover, the reversibility of epigenetic modifications, in contrast to the irreversibility of genetic changes, has made the epigenetic machinery an attractive target for drug development. This review summarizes the most advanced applications of epigenetic biomarkers and epigenetic drugs in the clinical setting, highlighting commercially available DNA methylation-based assays and epigenetic drugs already approved by the US Food and Drug Administration.
Topics: Humans; Epigenesis, Genetic; Neoplasms; DNA Methylation; Cell Transformation, Neoplastic
PubMed: 36512337
DOI: 10.3322/caac.21765 -
Molecular Cancer Jun 2023Cancer therapy resistance is the main cause of cancer treatment failure. The mechanism of therapy resistance is a hot topic in epigenetics. As one of the most common RNA... (Review)
Review
Cancer therapy resistance is the main cause of cancer treatment failure. The mechanism of therapy resistance is a hot topic in epigenetics. As one of the most common RNA modifications, N6-methyladenosine (m6A) is involved in various processes of RNA metabolism, such as stability, splicing, transcription, translation, and degradation. A large number of studies have shown that m6A RNA methylation regulates the proliferation and invasion of cancer cells, but the role of m6A in cancer therapy resistance is unclear. In this review, we summarized the research progress related to the role of m6A in regulating therapy resistance in cancers.
Topics: Humans; Methylation; Neoplasms; RNA Splicing; Epigenesis, Genetic; RNA
PubMed: 37264402
DOI: 10.1186/s12943-023-01782-2 -
Cancer Letters May 2023Patient-derived organoids (PDO) are a new biomedical research model that can reconstruct phenotypic and genetic characteristics of the original tissue and are useful for... (Review)
Review
Patient-derived organoids (PDO) are a new biomedical research model that can reconstruct phenotypic and genetic characteristics of the original tissue and are useful for research on pathogenesis and drug screening. To introduce the progression in this field, we review the key factors of constructing organoids derived from epithelial tissues and cancers, covering culture medium and matrix, morphological characteristics, genetic profiles, high-throughput drug screening, and application potential. We also discuss the co-culture system of cancer organoids with tumor microenvironment (TME) associated cells. The co-culture system is widely used in evaluating crosstalk of cancer cells with TME components, such as fibroblasts, endothelial cells, immune cells, and microorganisms. The article provides a prospective for standardized cultivation mode, automatic morphological evaluation, and drug sensitivity screening using high-throughput methods.
Topics: Humans; Drug Evaluation, Preclinical; Endothelial Cells; Prospective Studies; Neoplasms; Organoids; Tumor Microenvironment
PubMed: 37061121
DOI: 10.1016/j.canlet.2023.216180 -
Molecular Cancer Aug 2023Recent advances in neoantigen research have accelerated the development of tumor immunotherapies, including adoptive cell therapies (ACTs), cancer vaccines and... (Review)
Review
Recent advances in neoantigen research have accelerated the development of tumor immunotherapies, including adoptive cell therapies (ACTs), cancer vaccines and antibody-based therapies, particularly for solid tumors. With the development of next-generation sequencing and bioinformatics technology, the rapid identification and prediction of tumor-specific antigens (TSAs) has become possible. Compared with tumor-associated antigens (TAAs), highly immunogenic TSAs provide new targets for personalized tumor immunotherapy and can be used as prospective indicators for predicting tumor patient survival, prognosis, and immune checkpoint blockade response. Here, the identification and characterization of neoantigens and the clinical application of neoantigen-based TCR-T immunotherapy strategies are summarized, and the current status, inherent challenges, and clinical translational potential of these strategies are discussed.
Topics: Humans; Prospective Studies; Neoplasms; Cancer Vaccines; T-Lymphocytes; Receptors, Antigen, T-Cell
PubMed: 37649123
DOI: 10.1186/s12943-023-01844-5 -
Nutrients Oct 2023Cancer is amenable to low-cost treatments, given that it has a significant metabolic component, which can be affected through diet and lifestyle change at minimal cost.... (Review)
Review
Cancer is amenable to low-cost treatments, given that it has a significant metabolic component, which can be affected through diet and lifestyle change at minimal cost. The Warburg hypothesis states that cancer cells have an altered cell metabolism towards anaerobic glycolysis. Given this metabolic reprogramming in cancer cells, it is possible to target cancers metabolically by depriving them of glucose. In addition to dietary and lifestyle modifications which work on tumors metabolically, there are a panoply of nutritional supplements and repurposed drugs associated with cancer prevention and better treatment outcomes. These interventions and their evidentiary basis are covered in the latter half of this review to guide future cancer treatment.
Topics: Humans; Neoplasms; Glycolysis; Energy Metabolism; Treatment Outcome
PubMed: 37836529
DOI: 10.3390/nu15194245 -
Biochimica Et Biophysica Acta. Reviews... Jul 2023The development of new antitumor drugs depends mainly upon targeting tumor cells precisely. Trophoblast surface antigen 2 (Trop-2) is a type I transmembrane glycoprotein... (Review)
Review
The development of new antitumor drugs depends mainly upon targeting tumor cells precisely. Trophoblast surface antigen 2 (Trop-2) is a type I transmembrane glycoprotein involved in Ca signaling in tumor cells. It is highly expressed in various tumor tissues than in normal tissues and represents a novel and promising molecular target for caner targeted therapy. Up to now, the mechanisms and functions associated with Trop-2 have been extensively studied in a variety of solid tumors. According to these findings, Trop-2 plays an important role in cell proliferation, apoptosis, cell adhesion, epithelial-mesenchymal transition, as well as tumorigenesis and tumor progression. In addition, Trop-2 related drugs are also being developed widely. There are a number of Trop-2 related ADC drugs that have demonstrated potent antitumor activity and are currently been studied, such as Sacituzumab Govitecan (SG) and Datopotamab Deruxtecan (Dato-Dxd). In this study, we reviewed the progress of Trop-2 research in solid tumors. We also sorted out the composition and rationale of Trop-2 related drugs and summarized the related clinical trials. Finally, we discussed the current status of Trop-2 research and expanded our perspectives on its future research directions. Importantly, we found that Trop-2 targeted ADCs have great potential for combination with other antitumor therapies. Trop-2 targeted ADCs can reprogramme tumor microenvironment through multiple signaling pathways, ultimately activating antitumor immunity.
Topics: Humans; Neoplasms; Antineoplastic Agents; Apoptosis; Tumor Microenvironment
PubMed: 37121444
DOI: 10.1016/j.bbcan.2023.188902 -
Journal of Hematology & Oncology Nov 2023Research into the potential benefits of artificial intelligence for comprehending the intricate biology of cancer has grown as a result of the widespread use of deep... (Review)
Review
Research into the potential benefits of artificial intelligence for comprehending the intricate biology of cancer has grown as a result of the widespread use of deep learning and machine learning in the healthcare sector and the availability of highly specialized cancer datasets. Here, we review new artificial intelligence approaches and how they are being used in oncology. We describe how artificial intelligence might be used in the detection, prognosis, and administration of cancer treatments and introduce the use of the latest large language models such as ChatGPT in oncology clinics. We highlight artificial intelligence applications for omics data types, and we offer perspectives on how the various data types might be combined to create decision-support tools. We also evaluate the present constraints and challenges to applying artificial intelligence in precision oncology. Finally, we discuss how current challenges may be surmounted to make artificial intelligence useful in clinical settings in the future.
Topics: Humans; Artificial Intelligence; Neoplasms; Precision Medicine; Machine Learning; Medical Oncology
PubMed: 38012673
DOI: 10.1186/s13045-023-01514-5 -
International Journal of Epidemiology Jun 2023Genetic and lifestyle factors are associated with cancer risk. We investigated the benefits of adhering to lifestyle advice by the World Cancer Research Fund (WCRF) with...
BACKGROUND
Genetic and lifestyle factors are associated with cancer risk. We investigated the benefits of adhering to lifestyle advice by the World Cancer Research Fund (WCRF) with the risk of 13 types of cancer and whether these associations differ according to genetic risk using data from the UK Biobank.
METHODS
In 2006-2010, participants aged 37-73 years had their lifestyle assessed and were followed up for incident cancers until 2015-2019. Analyses were restricted to those of White European ancestry with no prior history of malignant cancer (n = 195 822). Polygenic risk scores (PRSs) were computed for 13 cancer types and these cancers combined ('overall cancer'), and a lifestyle index was calculated from WCRF recommendations. Associations with cancer incidence were estimated using Cox regression, adjusting for relevant confounders. Additive and multiplicative interactions between lifestyle index and PRSs were assessed.
RESULTS
There were 15 240 incident cancers during the 1 926 987 person-years of follow-up (median follow-up = 10.2 years). After adjusting for confounders, the lifestyle index was associated with a lower risk of overall cancer [hazard ratio per standard deviation increase (95% CI) = 0.89 (0.87, 0.90)] and of eight specific cancer types. There was no evidence of interactions on the multiplicative scale. There was evidence of additive interactions in risks for colorectal, breast, pancreatic, lung and bladder cancers, such that the recommended lifestyle was associated with greater change in absolute risk for persons at higher genetic risk (P < 0.0003 for all).
CONCLUSIONS
The recommended lifestyle has beneficial associations with most cancers. In terms of absolute risk, the protective association is greater for higher genetic risk groups for some cancers. These findings have important implications for persons most genetically predisposed to those cancers and for targeted strategies for cancer prevention.
Topics: Humans; Incidence; Prospective Studies; Risk Factors; Life Style; Neoplasms
PubMed: 36651198
DOI: 10.1093/ije/dyac238