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      Leveraging the intratumoral microbiota to treat human cancer: are engineered exosomes an effective strategy?

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          Abstract

          Cancer remains a leading cause of global mortality. The tumor microbiota has increasingly been recognized as a key regulator of cancer onset and progression, in addition to shaping tumor responses to immunotherapy. Microbes, including viruses, bacteria, fungi, and other eukaryotic species can impact the internal homeostasis and health of humans. Research focused on the gut microflora and the intratumoral microbiome has revolutionized the current understanding of how tumors grow, progress, and resist therapeutic interventions. Even with this research, however, there remains relatively little that is known with respect to the abundance of microbes and their effects on tumors and the tumor microenvironment. Engineered exosomes are a class of artificial extracellular nanovesicles that can actively transport small molecule drugs and nucleic acids, which have the broad prospects of tumor cell therapy. The present review offers an overview of recent progress and challenges associated with the intratumoral microbiome and engineered exosomes in the context of cancer research. These discussions are used to inform the construction of a novel framework for engineered exosome-mediated targeted drug delivery, taking advantage of intratumoral microbiota diversity as a strategic asset and thereby providing new opportunities to more effectively treat and manage cancer in the clinic.

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          Cancer statistics, 2024

          Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths in the United States and compiles the most recent data on population‐based cancer occurrence and outcomes using incidence data collected by central cancer registries (through 2020) and mortality data collected by the National Center for Health Statistics (through 2021). In 2024, 2,001,140 new cancer cases and 611,720 cancer deaths are projected to occur in the United States. Cancer mortality continued to decline through 2021, averting over 4 million deaths since 1991 because of reductions in smoking, earlier detection for some cancers, and improved treatment options in both the adjuvant and metastatic settings. However, these gains are threatened by increasing incidence for 6 of the top 10 cancers. Incidence rates increased during 2015–2019 by 0.6%–1% annually for breast, pancreas, and uterine corpus cancers and by 2%–3% annually for prostate, liver (female), kidney, and human papillomavirus‐associated oral cancers and for melanoma. Incidence rates also increased by 1%–2% annually for cervical (ages 30–44 years) and colorectal cancers (ages <55 years) in young adults. Colorectal cancer was the fourth‐leading cause of cancer death in both men and women younger than 50 years in the late‐1990s but is now first in men and second in women. Progress is also hampered by wide persistent cancer disparities; compared to White people, mortality rates are two‐fold higher for prostate, stomach and uterine corpus cancers in Black people and for liver, stomach, and kidney cancers in Native American people. Continued national progress will require increased investment in cancer prevention and access to equitable treatment, especially among American Indian and Alaska Native and Black individuals.
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            Tumour heterogeneity and resistance to cancer therapies

            Cancer is a dynamic disease. During the course of disease, cancers generally become more heterogeneous. As a result of this heterogeneity, the bulk tumour might include a diverse collection of cells harbouring distinct molecular signatures with differential levels of sensitivity to treatment. This heterogeneity might result in a non-uniform distribution of genetically distinct tumour-cell subpopulations across and within disease sites (spatial heterogeneity) or temporal variations in the molecular makeup of cancer cells (temporal heterogeneity). Heterogeneity provides the fuel for resistance; therefore, an accurate assessment of tumour heterogeneity is essential for the development of effective therapies. Multiregion sequencing, single-cell sequencing, analysis of autopsy samples, and longitudinal analysis of liquid biopsy samples are all emerging technologies with considerable potential to dissect the complex clonal architecture of cancers. In this Review, we discuss the driving forces behind intratumoural heterogeneity and the current approaches used to combat this heterogeneity and its consequences. We also explore how clinical assessments of tumour heterogeneity might facilitate the development of more-effective personalized therapies.
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              The human tumor microbiome is composed of tumor type–specific intracellular bacteria

              Bacteria were first detected in human tumors more than 100 years ago, but the characterization of the tumor microbiome has remained challenging because of its low biomass. We undertook a comprehensive analysis of the tumor microbiome, studying 1526 tumors and their adjacent normal tissues across seven cancer types, including breast, lung, ovary, pancreas, melanoma, bone, and brain tumors. We found that each tumor type has a distinct microbiome composition and that breast cancer has a particularly rich and diverse microbiome. The intratumor bacteria are mostly intracellular and are present in both cancer and immune cells. We also noted correlations between intratumor bacteria or their predicted functions with tumor types and subtypes, patients’ smoking status, and the response to immunotherapy.
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                Author and article information

                Journal
                J Transl Med
                J Transl Med
                Journal of Translational Medicine
                BioMed Central (London )
                1479-5876
                5 August 2024
                5 August 2024
                2024
                : 22
                : 728
                Affiliations
                [1 ]Department of Breast and Thyroid Surgery, Shaoxing People’s Hospital, ( https://ror.org/05v58y004) Shaoxing, Zhejiang Province 312000 China
                [2 ]Department of Medical Research Center, Shaoxing People’s Hospital, ( https://ror.org/05v58y004) Shaoxing, Zhejiang Province 312000 China
                [3 ]Department of Vascular Hernia Surgery, Shaoxing People’s Hospital, ( https://ror.org/05v58y004) Shaoxing, Zhejiang Province 312000 China
                [4 ]Department of Radiotherapy, Shaoxing People’s Hospital, ( https://ror.org/05v58y004) Shaoxing, Zhejiang Province 312000 China
                [5 ]GRID grid.452853.d, Department of Burn and Plastic Surgery-Hand Surgery, , Changshu Hospital Affiliated to Soochow University, Changshu No.1 People’s Hospital, ; Changshu, Jiangsu Province 215500 China
                [6 ]Cancer Center, Department of Breast Surgery, Zhejiang Provincial People’s Hospital (Affiliated People ’ s Hospital), Hangzhou Medical College, Hangzhou, Zhejiang Province 310014 China
                Author information
                http://orcid.org/0000-0003-0493-871X
                http://orcid.org/0000-0002-6062-8161
                Article
                5531
                10.1186/s12967-024-05531-x
                11302114
                39103887
                8433383f-0031-4b58-a764-891309dc396a
                © The Author(s) 2024

                Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it.The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.

                History
                : 27 April 2024
                : 23 July 2024
                Funding
                Funded by: Da Qian
                Award ID: SKYD2022049
                Award Recipient :
                Categories
                Review
                Custom metadata
                © BioMed Central Ltd., part of Springer Nature 2024

                Medicine
                cancer,intratumoral microbiota,engineering exosomes,tumor microenvironment,treatment
                Medicine
                cancer, intratumoral microbiota, engineering exosomes, tumor microenvironment, treatment

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