Radiotherapy combined with immunotherapy: the dawn of cancer treatment

Signal Transduction and Targeted Therapy, Год журнала: 2022, Номер 7(1)

Опубликована: Июль 29, 2022

Abstract Radiotherapy (RT) is delivered for purposes of local control, but can also exert systemic effect on remote and non-irradiated tumor deposits, which called abscopal effect. The view RT as a simple treatment has dramatically changed in recent years, it now widely accepted that provoke immune response gives strong rationale the combination immunotherapy (iRT). Nevertheless, several points remain to be addressed such interaction system, identification best schedules with (IO), expansion mechanism amplify iRT. To answer these crucial questions, we roundly summarize underlying showing whole landscape clinical trials attempt identify In consideration rarity effect, propose occurrence induced by radiation promoted 100% molecular genetic level. Furthermore, “radscopal effect” refers using low-dose reprogram microenvironment may overcome resistance Taken together, could regarded trigger antitumor response, help IO used radical added into current standard regimen patients metastatic cancer.

Язык: Английский

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Three-Dimensional Spheroids as In Vitro Preclinical Models for Cancer Research

Pharmaceutics, Год журнала: 2020, Номер 12(12), С. 1186 - 1186

Опубликована: Дек. 6, 2020

Most cancer biologists still rely on conventional two-dimensional (2D) monolayer culture techniques to test in vitro anti-tumor drugs prior vivo testing. However, the vast majority of promising preclinical have no or weak efficacy real patients with tumors, thereby delaying discovery successful therapeutics. This is because 2D lacks cell–cell contacts and natural tumor microenvironment, important signaling drug response, resulting a reduced malignant phenotype compared tumor. In this sense, three-dimensional (3D) cultures cells that better recapitulate cell environments emerged as scientifically accurate low cost models for screening testing new candidates before moving expensive time-consuming animal models. Here, we provide comprehensive overview 3D systems highlight strategies spheroid construction evaluation tools targeted therapies, focusing their applicability research. Examples therapeutic nanomedicines are discussed.

Язык: Английский

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Nanozymes-recent development and biomedical applications

Journal of Nanobiotechnology, Год журнала: 2022, Номер 20(1)

Опубликована: Фев. 22, 2022

Nanozyme is a series of nanomaterials with enzyme-mimetic activities that can proceed the catalytic reactions natural enzymes. In field biomedicine, nanozymes are capturing tremendous attention due to their high stability and low cost. Enzyme-mimetic be regulated by multiple factors, such as chemical state metal ion, pH, hydrogen peroxide (H2O2), glutathione (GSH) level, presenting great promise for biomedical applications. Over past decade, multi-functional have been developed various To promote understandings development novel multifunctional nanozymes, we herein provide comprehensive review applications in field. Nanozymes versatile enzyme-like properties briefly overviewed, mechanism application discussed future research. Finally, underlying challenges prospects frontier this review.

Язык: Английский

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Programmed Cell Death Tunes Tumor Immunity

Frontiers in Immunology, Год журнала: 2022, Номер 13

Опубликована: Март 30, 2022

The demise of cells in various ways enables the body to clear unwanted cells. Studies over years revealed distinctive molecular mechanisms and functional consequences several key cell death pathways. Currently, most intensively investigated programmed (PCD) includes apoptosis, necroptosis, pyroptosis, ferroptosis, PANoptosis, autophagy, which has been discovered play crucial roles modulating immunosuppressive tumor microenvironment (TME) determining clinical outcomes cancer therapeutic approaches. PCD can dual roles, either pro-tumor or anti-tumor, partly depending on intracellular contents released during process. also regulates enrichment effector regulatory immune cells, thus participating fine-tuning anti-tumor immunity TME. In this review, we focused primarily discussed messengers regulating their intricate crosstalk with response TME, explored immunological consequence its implications future therapy developments.

Язык: Английский

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The Role of Cancer Stem Cells in Radiation Resistance

Frontiers in Oncology, Год журнала: 2020, Номер 10

Опубликована: Фев. 20, 2020

Cancer stem cells (CSC) are a distinct subpopulation within tumor. They able to self-renew and differentiate possess high capability repair DNA damage, exhibit low levels of reactive oxygen species (ROS), proliferate slowly. These features render CSC resistant various therapies, including radiation therapy (RT). Eradication as many possible is requirement for an effective antineoplastic treatment therefore utmost importance the patient. This makes prime targets any therapeutic approach. Albeit clinical data still scarce, experimental first trials give hope that CSC-based has potential improve treatment, especially tumors known be resistant, such glioblastoma. In this review, we will discuss in context RT, describe mechanisms resistance, examine possibilities biomarkers, new approaches.

Язык: Английский

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CSC Radioresistance: A Therapeutic Challenge to Improve Radiotherapy Effectiveness in Cancer

Cells, Год журнала: 2020, Номер 9(7), С. 1651 - 1651

Опубликована: Июль 9, 2020

Radiotherapy (RT) is a modality of oncologic treatment that can be used to treat approximately 50% all cancer patients either alone or in combination with other modalities such as surgery, chemotherapy, immunotherapy, and therapeutic targeting. Despite the technological advances RT, which allow more precise delivery radiation while progressively minimizing impact on normal tissues, issues like radioresistance tumor recurrence remain important challenges. Tumor heterogeneity responsible for variation response different subpopulations. A main factor related presence stem cells (CSC) inside tumors, are metastases, relapses, RT failure, poor prognosis patients. The plasticity CSCs, process highly dependent epithelial–mesenchymal transition (EMT) associated cell dedifferentiation, complicates identification eradication CSCs it might involved disease relapse progression after irradiation. microenvironment interactions their niches also play an role RT. This review provides deep insight into characteristics mechanisms both primary metastasis radiation, radiobiological principles CSC Finally, we summarize major clinical trials development CSC-based therapies combined overcome radioresistance. better understanding potential targets radiosensitization will provide safer efficient strategies, turn improve live expectancy curability

Язык: Английский

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Low dose ionizing radiation effects on the immune system

Environment International, Год журнала: 2020, Номер 149, С. 106212 - 106212

Опубликована: Дек. 5, 2020

Ionizing radiation interacts with the immune system in many ways a multiplicity that mirrors complexity of itself: namely need to maintain delicate balance between different compartments, cells and soluble factors work collectively protect, maintain, restore tissue function face severe challenges including damage. The cytotoxic effects high dose are less relevant after low exposure, where subtle quantitative functional predominate may go unnoticed until late exposure or second challenge reveals exacerbates effects. For example, doses permanently alter fitness therefore accelerate senescence pave way for wide spectrum possible pathophysiological events, early-onset age-related degenerative disorders cancer. By contrast, so called therapy displays beneficial, anti-inflammatory pain relieving properties chronic inflammatory diseases. In this review, epidemiological, clinical experimental data regarding low-dose on homeostasis integrity will be discussed, as role immune-mediated mechanisms systemic manifestation localized exposures such reactions. central conclusion is ionizing fundamentally durably reshapes system. Further, importance discovery immunological pathways modifying resilience amongst other research directions field implied.

Язык: Английский

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Exosomal miRNAs in tumor microenvironment

Journal of Experimental & Clinical Cancer Research, Год журнала: 2020, Номер 39(1)

Опубликована: Апрель 16, 2020

Tumor microenvironment (TME) is the internal environment in which tumor cells survive, consisting of cells, fibroblasts, endothelial and immune as well non-cellular components, such exosomes cytokines. Exosomes are tiny extracellular vesicles (40-160nm) containing active substances, proteins, lipids nucleic acids. carry biologically miRNAs to shuttle between TME, thereby affecting development. Tumor-derived exosomal induce matrix reprogramming creating a that conducive growth, metastasis, escape chemotherapy resistance. In this review, we updated role process TME reshaping.

Язык: Английский

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Interfering with Tumor Hypoxia for Radiotherapy Optimization

Journal of Experimental & Clinical Cancer Research, Год журнала: 2021, Номер 40(1)

Опубликована: Июнь 21, 2021

Hypoxia in solid tumors is an important predictor of treatment resistance and poor clinical outcome. The significance hypoxia the development to radiotherapy has been recognized for decades search hypoxia-targeting, radiosensitizing agents continues. This review summarizes main hypoxia-related processes relevant on subcellular, cellular tissue level discusses radiation oncology, especially with regard current shift towards hypofractionated regimens. Furthermore, we discuss strategies interfere optimization, highlight novel insights into molecular pathways involved that might be utilized increase efficacy radiotherapy.

Язык: Английский

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The Tumor Microenvironment in Tumorigenesis and Therapy Resistance Revisited

Cancers, Год журнала: 2023, Номер 15(2), С. 376 - 376

Опубликована: Янв. 6, 2023

Tumorigenesis is a complex and dynamic process involving cell-cell cell-extracellular matrix (ECM) interactions that allow tumor cell growth, drug resistance metastasis. This review provides an updated summary of the role played by microenvironment (TME) components hypoxia in tumorigenesis, highlight various ways through which cells reprogram normal into phenotypes are pro-tumorigenic, including cancer associated- fibroblasts, -macrophages -endothelial cells. Tumor secrete numerous factors leading to transformation previously anti-tumorigenic environment pro-tumorigenic environment. Once formed, solid tumors continue interact with stromal cells, local infiltrating macrophages, mesenchymal stem endothelial pericytes, secreted ECM within (TME). The TME key response treatment outcome. Importantly, can initially be anti-tumorigenic, but over time promote tumorigenesis induce therapy resistance. To counter hypoxia, increased angiogenesis leads formation new vascular networks order actively sustain growth via supply oxygen nutrients, whilst removing metabolic waste. Angiogenic network aid metastatic dissemination. Successful novel development require identification therapeutic targeting cancer-associated- fibroblasts (CAFs) (CAMs), blocking ECM-receptor interactions, addition reprogramming immune success. Lastly, this highlights potential TME- hypoxia-centered therapies under investigation.

Язык: Английский

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