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      Pseudomonas aeruginosa in Cancer Therapy: Current Knowledge, Challenges and Future Perspectives

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          Abstract

          Drug resistance, undesirable toxicity and lack of selectivity are the major challenges of conventional cancer therapies, which cause poor clinical outcomes and high mortality in many cancer patients. Development of alternative cancer therapeutics are highly required for the patients who are resistant to the conventional cancer therapies, including radiotherapy and chemotherapy. The success of a new cancer therapy depends on its high specificity to cancer cells and low toxicity to normal cells. Utilization of bacteria has emerged as a promising strategy for cancer treatment. Attenuated or genetically modified bacteria were used to inhibit tumor growth, modulate host immunity, or deliver anti-tumor agents. The bacteria-derived immunotoxins were capable of destructing tumors with high specificity. These bacteria-based strategies for cancer treatment have shown potent anti-tumor effects both in vivo and in vitro, and some of them have proceeded to clinical trials. Pseudomonas aeruginosa, a Gram-negative bacterial pathogen, is one of the common bacteria used in development of bacteria-based cancer therapy, particularly known for the Pseudomonas exotoxin A-based immunotoxins, which have shown remarkable anti-tumor efficacy and specificity. This review concisely summarizes the current knowledge regarding the utilization of P. aeruginosa in cancer treatment, and discusses the challenges and future perspectives of the P. aeruginosa-based therapeutic strategies.

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          Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries

          This article provides an update on the global cancer burden using the GLOBOCAN 2020 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer. Worldwide, an estimated 19.3 million new cancer cases (18.1 million excluding nonmelanoma skin cancer) and almost 10.0 million cancer deaths (9.9 million excluding nonmelanoma skin cancer) occurred in 2020. Female breast cancer has surpassed lung cancer as the most commonly diagnosed cancer, with an estimated 2.3 million new cases (11.7%), followed by lung (11.4%), colorectal (10.0 %), prostate (7.3%), and stomach (5.6%) cancers. Lung cancer remained the leading cause of cancer death, with an estimated 1.8 million deaths (18%), followed by colorectal (9.4%), liver (8.3%), stomach (7.7%), and female breast (6.9%) cancers. Overall incidence was from 2-fold to 3-fold higher in transitioned versus transitioning countries for both sexes, whereas mortality varied <2-fold for men and little for women. Death rates for female breast and cervical cancers, however, were considerably higher in transitioning versus transitioned countries (15.0 vs 12.8 per 100,000 and 12.4 vs 5.2 per 100,000, respectively). The global cancer burden is expected to be 28.4 million cases in 2040, a 47% rise from 2020, with a larger increase in transitioning (64% to 95%) versus transitioned (32% to 56%) countries due to demographic changes, although this may be further exacerbated by increasing risk factors associated with globalization and a growing economy. Efforts to build a sustainable infrastructure for the dissemination of cancer prevention measures and provision of cancer care in transitioning countries is critical for global cancer control.
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            Hallmarks of Cancer: The Next Generation

            The hallmarks of cancer comprise six biological capabilities acquired during the multistep development of human tumors. The hallmarks constitute an organizing principle for rationalizing the complexities of neoplastic disease. They include sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, and activating invasion and metastasis. Underlying these hallmarks are genome instability, which generates the genetic diversity that expedites their acquisition, and inflammation, which fosters multiple hallmark functions. Conceptual progress in the last decade has added two emerging hallmarks of potential generality to this list-reprogramming of energy metabolism and evading immune destruction. In addition to cancer cells, tumors exhibit another dimension of complexity: they contain a repertoire of recruited, ostensibly normal cells that contribute to the acquisition of hallmark traits by creating the "tumor microenvironment." Recognition of the widespread applicability of these concepts will increasingly affect the development of new means to treat human cancer. Copyright © 2011 Elsevier Inc. All rights reserved.
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              Antibiotic resistance in Pseudomonas aeruginosa: mechanisms and alternative therapeutic strategies

              Pseudomonas aeruginosa is an opportunistic pathogen that is a leading cause of morbidity and mortality in cystic fibrosis patients and immunocompromised individuals. Eradication of P. aeruginosa has become increasingly difficult due to its remarkable capacity to resist antibiotics. Strains of Pseudomonas aeruginosa are known to utilize their high levels of intrinsic and acquired resistance mechanisms to counter most antibiotics. In addition, adaptive antibiotic resistance of P. aeruginosa is a recently characterized mechanism, which includes biofilm-mediated resistance and formation of multidrug-tolerant persister cells, and is responsible for recalcitrance and relapse of infections. The discovery and development of alternative therapeutic strategies that present novel avenues against P. aeruginosa infections are increasingly demanded and gaining more and more attention. Although mostly at the preclinical stages, many recent studies have reported several innovative therapeutic technologies that have demonstrated pronounced effectiveness in fighting against drug-resistant P. aeruginosa strains. This review highlights the mechanisms of antibiotic resistance in P. aeruginosa and discusses the current state of some novel therapeutic approaches for treatment of P. aeruginosa infections that can be further explored in clinical practice.
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                Author and article information

                Contributors
                Journal
                Front Oncol
                Front Oncol
                Front. Oncol.
                Frontiers in Oncology
                Frontiers Media S.A.
                2234-943X
                28 April 2022
                2022
                : 12
                : 891187
                Affiliations
                [1] 1 Innovative Institute of Chinese Medicine and Pharmacy, Shandong University of Traditional Chinese Medicine , Jinan, China
                [2] 2 School of Art & Design, Qilu University of Technology (Shandong Academy of Sciences) , Jinan, China
                Author notes

                Edited by: Giulio Fracasso, University of Verona, Italy

                Reviewed by: Rodolfo Ippoliti, University of L’Aquila, Italy; Achim Rothe, University Hospital of Cologne, Germany

                *Correspondence: Zheng Pang, 60230021@ 123456sdutcm.edu.cn ; Tong Tang, tangtong@ 123456qlu.edu.cn

                This article was submitted to Cancer Immunity and Immunotherapy, a section of the journal Frontiers in Oncology

                Article
                10.3389/fonc.2022.891187
                9095937
                35574361
                d71e6b58-19b1-4038-8936-cdce9ad7eca3
                Copyright © 2022 Pang, Gu and Tang

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 07 March 2022
                : 04 April 2022
                Page count
                Figures: 1, Tables: 1, Equations: 0, References: 134, Pages: 10, Words: 3930
                Funding
                Funded by: National Natural Science Foundation of China , doi 10.13039/501100001809;
                Categories
                Oncology
                Mini Review

                Oncology & Radiotherapy
                pseudomonas aeruginosa,cancer therapy,anti-cancer agent,vector,immunotoxin
                Oncology & Radiotherapy
                pseudomonas aeruginosa, cancer therapy, anti-cancer agent, vector, immunotoxin

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