Targeting cell death pathways for cancer therapy: recent developments in necroptosis, pyroptosis, ferroptosis, and cuproptosis research

Journal of Hematology & Oncology, Journal Year: 2022, Volume and Issue: 15(1)

Published: Dec. 8, 2022

Abstract Many types of human cells self-destruct to maintain biological homeostasis and defend the body against pathogenic substances. This process, called regulated cell death (RCD), is important for various activities, including clearance aberrant cells. Thus, RCD pathways represented by apoptosis have increased in importance as a target development cancer medications recent years. However, because tumor show avoidance apoptosis, which causes treatment resistance recurrence, numerous studies been devoted alternative mortality processes, namely necroptosis, pyroptosis, ferroptosis, cuproptosis; these modalities extensively studied shown be crucial therapy effectiveness. Furthermore, evidence suggests that undergoing may alter immunogenicity microenvironment (TME) some extent, rendering it more suitable inhibiting progression metastasis. In addition, other components TME undergo abovementioned forms induce immune attacks on cells, resulting enhanced antitumor responses. Hence, this review discusses molecular processes features cuproptosis effects novel proliferation Importantly, introduces complex affect biology. It also summarizes potential agents nanoparticles or inhibit their therapeutic based from vivo vitro reports clinical trials inducers evaluated treatments patients. Lastly, we summarized impact modulating drug advantages adding modulators over conventional treatments.

Language: Английский

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Current advance of nanotechnology in diagnosis and treatment for malignant tumors

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Aug. 12, 2024

Cancer remains a significant risk to human health. Nanomedicine is new multidisciplinary field that garnering lot of interest and investigation. shows great potential for cancer diagnosis treatment. Specifically engineered nanoparticles can be employed as contrast agents in diagnostics enable high sensitivity high-resolution tumor detection by imaging examinations. Novel approaches labeling are also made possible the use nanoprobes nanobiosensors. The achievement targeted medication delivery therapy accomplished through rational design manufacture nanodrug carriers. Nanoparticles have capability effectively transport medications or gene fragments tissues via passive active targeting processes, thus enhancing treatment outcomes while minimizing harm healthy tissues. Simultaneously, context radiation sensitization photothermal enhance therapeutic efficacy malignant tumors. This review presents literature overview summary how nanotechnology used According oncological diseases originating from different systems body combining pathophysiological features cancers at sites, we most recent developments applications. Finally, briefly discuss prospects challenges cancer.

Language: Английский

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Cardiovascular disease: Mitochondrial dynamics and mitophagy crosstalk mechanisms with novel programmed cell death and macrophage polarisation

Pharmacological Research, Journal Year: 2024, Volume and Issue: 206, P. 107258 - 107258

Published: June 21, 2024

Several cardiovascular illnesses are associated with aberrant activation of cellular pyroptosis, ferroptosis, necroptosis, cuproptosis, disulfidptosis and macrophage polarisation as hallmarks contributing to vascular damage abnormal cardiac function. Meanwhile, these three novel forms dysfunction closely related mitochondrial homeostasis. Mitochondria the main organelles that supply energy maintain Mitochondrial stability is maintained through a series regulatory pathways, such fission, fusion mitophagy. Studies have shown (e.g., impaired dynamics mitophagy) promotes ROS production, leading oxidative stress, which induces M1 phenotypic polarisation. Therefore, an in-depth knowledge dynamic regulation mitochondria during necessary understand disease development. This paper systematically summarises impact changes in mitophagy on regulating dysfunctions promote understanding pathogenesis diseases provide corresponding theoretical references for treating diseases.

Language: Английский

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Inhibition of CDC20 potentiates anti-tumor immunity through facilitating GSDME-mediated pyroptosis in prostate cancer

Experimental Hematology and Oncology, Journal Year: 2023, Volume and Issue: 12(1)

Published: Aug. 1, 2023

Abstract Background Increasing evidence suggests that immunotherapy, especially immune checkpoint inhibitors (ICIs), has the potential to facilitate long-term survival in various cancer besides prostate cancer. Emerging indicated pyroptosis, an immunogenic form of cell death, could trigger anti-tumor microenvironment and enhance effectiveness immunotherapy. Nevertheless, mechanism underlying regulation pyroptosis signaling remains unclear. Methods The differential expression human E3 ligases was integratedly analyzed from five independent public datasets. Moreover, immunohistochemistry analysis a tissue microarray derived patients confirmed results bioinformatic analysis. Furthermore, lines were evaluated via next-generation RNA sequencing assess transcriptomic profile upon CDC20 depletion. Next, qRT-PCR, Western blotting, cycloheximide assay, immunoprecipitation, ubiquitination assay employed explore correlation interaction between GSDME. Both immune-deficient immune-competent murine models utilized examine efficacy inhibition with or without anti-PD1 antibodies, respectively. To analyze xenografts, tumor tissues examined by flow cytometry. Results multiple cohorts suggested most significantly over-expressed ligase. In addition, exerted negative regulatory effect on pathway targeting GSDME for ubiquitination-mediated proteolysis degron-dependent manner. Knockdown leads increased abundance transition apoptosis response death signals. our syngeneic models, we found depletion enhances immunity promoting infiltration CD8 + T lymphocytes dependent existence GSDME, as well reducing myeloid cells. More importantly, Apcin, small molecular inhibitor targets CDC20, exhibited synergistic effects anti-PD1-based immunotherapy Conclusions Overall, these findings provide new insights into upstream GSDME-mediated which specifically interacts facilitates its Importantly, data highlight novel pathways cellular enhancing

Language: Английский

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Therapy resistance in neuroblastoma: Mechanisms and reversal strategies

Frontiers in Pharmacology, Journal Year: 2023, Volume and Issue: 14

Published: Feb. 16, 2023

Neuroblastoma is one of the most common pediatric solid tumors that threaten health children, accounting for about 15% childhood cancer-related mortality in United States. Currently, multiple therapies have been developed and applied clinic to treat neuroblastoma including chemotherapy, radiotherapy, targeted therapy, immunotherapy. However, resistance inevitable following long-term treatment, leading treatment failure cancer relapse. Hence, understand mechanisms therapy discover reversal strategies become an urgent task. Recent studies demonstrated numerous genetic alterations dysfunctional pathways related resistance. These molecular signatures may be potential targets combat refractory neuroblastoma. A number novel interventions patients based on these targets. In this review, we focus complicated such as ATP-binding cassette transporters, long non-coding RNAs, microRNAs, autophagy, stem cells, extracellular vesicles. On basis, summarized recent overcome targeting MYCN gene, hypoxia, autophagy. This review aims provide insight how improve efficacy against resistant neuroblastoma, which shed light future directions would enhance outcomes prolong survival with

Language: Английский

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Crosstalk of pyroptosis and cytokine in the tumor microenvironment: from mechanisms to clinical implication

Molecular Cancer, Journal Year: 2024, Volume and Issue: 23(1)

Published: Nov. 30, 2024

In the realm of cancer research, tumor microenvironment (TME) plays a crucial role in initiation and progression, shaped by complex interactions between cells surrounding non-cancerous cells. Cytokines, as essential immunomodulatory agents, are secreted various cellular constituents within TME, including immune cells, cancer-associated fibroblasts, themselves. These cytokines facilitate intricate communication networks that significantly influence initiation, metastasis, suppression. Pyroptosis contributes to TME remodeling promoting release pro-inflammatory sustaining chronic inflammation, impacting processes such escape angiogenesis. However, challenges remain due interplay among cytokines, pyroptosis, along with dual effects pyroptosis on progression therapy-related complications like cytokine syndrome. Unraveling these complexities could strategies balance inflammatory responses while minimizing tissue damage during therapy. This review delves into crosstalk elucidating their contribution metastasis. By synthesizing emerging therapeutic targets innovative technologies concerning this aims provide novel insights enhance treatment outcomes for patients.

Language: Английский

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Comprehensive Insights into Oral Squamous Cell Carcinoma: Diagnosis, Pathogenesis, and Therapeutic Advances

Pathology - Research and Practice, Journal Year: 2024, Volume and Issue: 261, P. 155489 - 155489

Published: July 27, 2024

Language: Английский

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The role of pyroptosis and gasdermin family in tumor progression and immune microenvironment

Experimental Hematology and Oncology, Journal Year: 2023, Volume and Issue: 12(1)

Published: Dec. 8, 2023

Abstract Pyroptosis, an inflammatory programmed cell death, distinguishes itself from apoptosis and necroptosis has drawn increasing attention. Recent studies have revealed a correlation between the expression levels of many pyroptosis-related genes both tumorigenesis progression. Despite advancements in cancer treatments such as surgery, radiotherapy, chemotherapy, immunotherapy, persistent hallmark enables malignant cells to elude death develop resistance therapy. findings indicate that pyroptosis can overcome amplify treatment-induced tumor death. Moreover, triggers antitumor immunity by releasing pro-inflammatory cytokines, augmenting macrophage phagocytosis, activating cytotoxic T natural killer cells. Additionally, it transforms “cold” tumors into “hot” tumors, thereby enhancing effects various treatments. Consequently, is intricately linked development holds promise effective strategy for boosting therapeutic efficacy. As principal executive protein pyroptosis, gasdermin family plays pivotal role influencing pyroptosis-associated outcomes serve regulatory target. This review provides comprehensive summary relationship members, discusses their roles progression immune microenvironment, analyses underlying strategies treatment based on pyroptotic

Language: Английский

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Etoposide: A rider on the cytokine storm

Cytokine, Journal Year: 2023, Volume and Issue: 168, P. 156234 - 156234

Published: June 1, 2023

Language: Английский

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Pyroptosis: A spoiler of peaceful coexistence between cells in degenerative bone and joint diseases

Journal of Advanced Research, Journal Year: 2024, Volume and Issue: unknown

Published: June 1, 2024

As people age, degenerative bone and joint diseases (DBJDs) become more prevalent. When middle-aged elderly are diagnosed with one or disorders such as osteoporosis (OP), osteoarthritis (OA), intervertebral disc degeneration (IVDD), it often signals the onset of prolonged pain reduced functionality. Chronic inflammation has been identified underlying cause various diseases, including DBJDs. Recently, excessive activation pyroptosis, a form programed cell death (PCD) mediated by inflammasomes, emerged primary driver harmful chronic inflammation. Consequently, pyroptosis potential target for preventing treating This review explored physiological pathological roles pathway in development its relation to Meanwhile, elaborated molecular mechanisms within individual types marrow joints, well interplay among different context Furthermore, this presented latest compelling evidence supporting idea regulating DBJDs treatment, discussed potential, limitations, challenges therapeutic strategies involving regulation. In summary, an interesting identity unregulated was proposed review, which undertaken spoiler peaceful coexistence between cells environment. Over extended course DBJDs, perpetuated activity through crosstalk cascades types, thus exacerbating inflammatory environment throughout entire Correspondingly, regulation therapy promising option clinical treatment

Language: Английский

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