Strategy For Cancer Treatment Research Articles

Smart nanocarriers for enzyme-activated prodrug therapy.

Exogenous enzyme-activated prodrug therapy (EPT) is a potential cancer treatment strategy that delivers non-human enzymes into or on the surface of the cell and subsequently converts a non-toxic prodrug into an active cytotoxic substance at a specific location and time. The development of several pharmacological pairs based on EPT has been the focus of anticancer research for more than three decades. Numerous of these pharmacological pairs have progressed to clinical trials, and a few have achieved application in specific cancer therapies. The current review highlights the potential of enzyme-activated prodrug therapy as a promising anticancer treatment. Different microbial, plant, or viral enzymes and their corresponding prodrugs that advanced to clinical trials have been listed. Additionally, we discuss new trends in the field of enzyme-activated prodrug nanocarriers, including nanobubbles combined with ultrasound (NB/US), mesoscopic-sized polyion complex vesicles (PICsomes), nanoparticles, and extracellular vesicles (EVs), with special emphasis on smart stimuli-triggered drug release, hybrid nanocarriers, and the main application of nanotechnology in improving prodrugs.

Unlocking the potential of bispecific ADCs for targeted cancer therapy.

Antibody-drug conjugates (ADCs) are biologically targeted drugs composed of antibodies and cytotoxic drugs connected by linkers. These innovative compounds enable precise drug delivery to tumor cells, minimizing harm to normal tissues and offering excellent prospects for cancer treatment. However, monoclonal antibody-based ADCs still present challenges, especially in terms of balancing efficacy and safety. Bispecific antibodies are alternatives to monoclonal antibodies and exhibit superior internalization and selectivity, producing ADCs with increased safety and therapeutic efficacy. In this review, we present available evidence and future prospects regarding the use of bispecific ADCs for cancer treatment, including a comprehensive overview of bispecific ADCs that are currently in clinical trials. We offer insights into the future development of bispecific ADCs to provide novel strategies for cancer treatment.

Clinicopathological, molecular, and prognostic features of colorectal carcinomas with KRAS c.34G>T (p.G12C) mutation.

Evidence indicates that combinations of anti-EGFR antibodies and KRAS p.G12C (c.34G>T) inhibitors can be an effective treatment strategy for advanced colorectal cancer. We hypothesized that KRAS c.34G>T (p.G12C)-mutated colorectal carcinoma might be a distinct tumor subtype. We utilized a prospective cohort incident tumor biobank (including 1347 colorectal carcinomas) and detected KRAS c.34G>T (p.G12C) mutation in 43 cases (3.2%) and other KRAS mutations (in codon 12, 13, 61, or 146) in 467 cases (35%). The CpG island methylator phenotype (CIMP)-low prevalence was similarly higher in KRAS c.34G>T mutants (52%) and other KRAS mutants (49%) than in KRAS-wild-type tumors (31%). KRAS c.34G>T mutants showed higher CIMP-high prevalence (14%) and lower CIMP-negative prevalence (33%) compared with other KRAS mutants (6% and 45%, respectively; p = 0.0036). Similar to other KRAS mutants, KRAS c.34G>T-mutated tumors were associated with cecal location, non-microsatellite instability (MSI)-high status, BRAF wild type, and PIK3CA mutation when compared with KRAS-wild-type tumors. Compared with BRAF-mutated tumors, KRAS c.34G>T mutants showed more frequent LINE-1 hypomethylation, a biomarker for early-onset colorectal carcinoma. KRAS c.34G>T mutants were not associated with other features, including the tumor tissue abundance of Fusobacterium nucleatum (F. animalis), pks+ Escherichia coli, Bifidobacterium, or (enterotoxigenic) Bacteroides fragilis. Among 1122 BRAF-wild-type colorectal carcinomas, compared with KRAS-wild-type tumors, multivariable-adjusted colorectal cancer-specific mortality hazard ratios (95% confidence interval) were 1.82 (1.05-3.17) in KRAS c.34G>T (p.G12C)-mutated tumors (p = 0.035) and 1.57 (1.22-2.02) in other KRAS-mutated tumors (p = 0.0004). Our study provides novel evidence for clinical and tumor characteristics of KRAS c.34G>T (p.G12C)-mutated colorectal carcinoma.

SUMO promotes DNA repair protein collaboration to support alternative telomere lengthening in the absence of PML.

The alternative lengthening of telomeres (ALT) pathway maintains telomere length in a significant fraction of cancers that are associated with poor clinical outcomes. A better understanding of ALT mechanisms is therefore necessary for developing new treatment strategies for ALT cancers. SUMO modification of telomere proteins contributes to the formation of ALT telomere-associated PML bodies (APBs), in which telomeres are clustered and DNA repair proteins are enriched to promote homology-directed telomere DNA synthesis in ALT. However, it is still unknown whether-and if so, how-SUMO supports ALT beyond APB formation. Here, we show that SUMO condensates that contain DNA repair proteins enable telomere maintenance in the absence of APBs. In PML knockout ALT cell lines that lack APBs, we found that SUMOylation is required for manifesting ALT features independent of PML and APBs. Chemically induced telomere targeting of SUMO produces condensate formation and ALT features in PML-null cells. This effect requires both SUMOylation and interactions between SUMO and SUMO interaction motifs (SIMs). Mechanistically, SUMO-induced effects are associated with the accumulation of DNA repair proteins, including Rad52, Rad51AP1, RPA, and BLM, at telomeres. Furthermore, Rad52 can undergo phase separation, enrich SUMO at telomeres, and promote telomere DNA synthesis in collaboration with the BLM helicase in a SUMO-dependent manner. Collectively, our findings suggest that SUMO condensate formation promotes collaboration among DNA repair factors to support ALT telomere maintenance without PML. Given the promising effects of SUMOylation inhibitors in cancer treatment, our findings suggest their potential use in perturbing telomere maintenance in ALT cancer cells.

Crosstalk Between MAPK and PI3K/AKT Signaling Pathways in Cellular Responses: Implications for Cancer Therapy

This research paper aims to explore the intricate crosstalk between the mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signaling pathways. These pathways play crucial roles in regulating cellular processes such as growth, proliferation, survival, and apoptosis. Dysregulation of these pathways is commonly associated with the development and progression of various cancers. By understanding the mechanisms of crosstalk between MAPK and PI3K/AKT pathways, this study seeks to identify potential therapeutic targets and strategies for more effective cancer treatment.

Discovery of Novel HDAC3 Inhibitors with PD-L1 Downregulating/Degrading and Antitumor Immune Effects.

Targeting the programmed cell death-1/ligand 1 (PD-1/PD-L1) pathway is one of the most promising cancer treatment strategies. Studies have shown that HDAC inhibitors can enhance the antitumor immune response by modulating the expression of PD-L1. Herein, we designed and synthesized a series of novel hydrazide-based small molecule HDAC inhibitors; among them, compound HQ-30 showed selective HDAC3 inhibition (IC50 = 89 nM) and remarkable PD-L1-degrading activity (DC50 = 5.7 μM, Dmax = 80% at 10 μM). Further studies revealed that HQ-30 induced the degradation of PD-L1 by regulating cathepsin B (CTSB) in the lysosomes. Further, HQ-30 could enhance the infiltration of CD3+ CD4+ helper T and CD3+ CD8+ cytotoxic T cells in tumors, thus activating the tumor immune microenvironment. Moreover, HQ-30 possessed a benign toxicity profile (LD50 > 1000 mg/kg) and favorable pharmacokinetic properties (F = 57%). Taken together, HQ-30 is worthy of further investigation as a small molecule-based epigenetic modulator of tumor immunotherapy.

TSP50 facilitates breast cancer stem cell-like properties maintenance and epithelial-mesenchymal transition via PI3K p110α mediated activation of AKT signaling pathway

BackgroundStudies have confirmed that epithelial-mesenchymal transition (EMT) and cancer stem cell (CSC)-like properties are conducive to cancer metastasis. In recent years, testes-specific protease 50 (TSP50) has been identified as a prognostic factor and is involved in tumorigenesis regulation. However, the role and molecular mechanisms of TSP50 in EMT and CSC-like properties maintenance remain unclear.MethodsThe expression and prognostic value of TSP50 in breast cancer were excavated from public databases and explored using bioinformatics analysis. Then the expression of TSP50 and related genes was further validated by quantitative RT-PCR (qRT-PCR), Western blot, and immunohistochemistry (IHC). In order to investigate the function of TSP50 in breast cancer, loss- and gain-of-function experiments were conducted, both in vitro and in vivo. Furthermore, immunofluorescence (IF) and immunoprecipitation (IP) assays were performed to explore the potential molecular mechanisms of TSP50. Finally, the correlation between the expression of TSP50 and related genes in breast cancer tissue microarray and clinicopathological characteristics was analyzed by IHC.ResultsTSP50 was negatively correlated with the prognosis of patients with breast cancer. TSP50 promoted CSC-like traits and EMT in both breast cancer cells and mouse xenograft tumor tissues. Additionally, inhibition of PI3K/AKT partly reversed TSP50-induced activation of CSC-like properties, EMT and tumorigenesis. Mechanistically, TSP50 and PI3K p85α regulatory subunit could competitively interact with the PI3K p110α catalytic subunit to promote p110α enzymatic activity, thereby activating the PI3K/AKT signaling pathway for CSC-like phenotypes maintenance and EMT promotion. Moreover, IHC analysis of human breast cancer specimens revealed that TSP50 expression was positively correlated with p-AKT and ALDH1 protein levels. Notably, breast cancer clinicopathological characteristics, such as patient survival time, tumor size, Ki67, pathologic stage, N stage, estrogen receptor (ER) and progesterone receptor (PR) levels, correlated well with TSP50/p-AKT/ALDH1 expression status.ConclusionThe effects of TSP50 on EMT and CSC-like properties promotion were verified to be dependent on PI3K p110α. Together, our study revealed a novel mechanism by which TSP50 facilitates the progression of breast cancer, which can provide new insights into TSP50-based breast cancer treatment strategies.

The role of gastric mucins and mucin-related glycans in gastric cancers.

Gastric mucins serve as a protective barrier on the stomach's surface, protecting from external stimuli including gastric acid and gut microbiota. Their composition typically changes in response to the metaplastic sequence triggered by Helicobacter pylori infection. This alteration in gastric mucins is also observed in cases of gastric cancer, although the precise connection between mucin expressions and gastric carcinogenesis remains uncertain. This review first introduces the relationship between mucin expressions and gastric metaplasia or cancer observed in humans and mice. Additionally, we discuss potential pathogenic mechanisms of how aberrant mucins and their glycans affect gastric carcinogenesis. Finally, we summarize challenges to target tumor-specific glycans by utilizing lectin-drug conjugates that can bind to specific glycans. Understanding the correlation and mechanism between these mucin expressions and gastric carcinogenesis could pave the way for new strategies in gastric cancer treatment.

Cancer-associated fibroblasts promote the malignant development of lung cancer through the FOXO1 protein/LIF signaling

This paper aims to investigate the current situation of cancer related fibroblasts promoting malignant development of cancer through FOXO1 protein/LIF signal, and explore the strategy of cancer treatment. Recent studies have shown that the expression of the protein forkhead box O1 (FOXO1) is increased in CAFsCAFs (Cancer-associated fibroblasts). This led researchers to investigate whether FOXO1 is involved in the role of CAFs in lung cancer. The results of the study revealed that FOXO1 is indeed upregulated in CAFs, and it positively regulates the transcription of another protein called LIF. Notably, LIF is also upregulated in both CAFs and lung cancer cells. These changes in protein expression were associated with the overexpression of FOXO1 in CAFs. Conversely, silencing FOXO1 in CAFs suppressed their effects on cancer cells and transplanted tumors. The study revealed that the downregulation of LIFR in cancer cells abolished the impact of CAFs overexpressing FOXO1 on cancer cell behavior. This suggests that the FOXO1/LIF signaling pathway is involved in mediating the malignant development of lung cancer induced by CAFs.

Histone demethylase PHF8 promotes prostate cancer metastasis via the E2F1-SNAI1 axis.

Metastasis is the primary culprit behind cancer-related fatalities in multiple cancer types, including prostate cancer. Despite great advances, the precise mechanisms underlying prostate cancer metastasis are far from complete. By using a transgenic mouse prostate cancer model (TRAMP) with and without Phf8 knockout, we have identified a crucial role of PHF8 in prostate cancer metastasis. By complexing with E2F1, PHF8 transcriptionally upregulates SNAI1 in a demethylation-dependent manner. The upregulated SNAI1 subsequently enhances epithelial-to-mesenchymal transition (EMT) and metastasis. Given the role of the abnormally activated PHF8/E2F1-SNAI1 axis in prostate cancer metastasis and poor prognosis, the levels of PHF8 or the activity of this axis could serve as biomarkers for prostate cancer metastasis. Moreover, targeting this axis could become a potential therapeutic strategy for prostate cancer treatment. © 2024 The Pathological Society of Great Britain and Ireland.

The regulation and function of Nrf2 signaling in ferroptosis-activated cancer therapy.

Ferroptosis is an iron-dependent programmed cell death process that involves lipid oxidation via the Fenton reaction to produce lipid peroxides, causing disruption of the lipid bilayer, which is essential for cellular survival. Ferroptosis has been implicated in the occurrence and treatment response of various types of cancer, and targeting ferroptosis has emerged as a promising strategy for cancer therapy. However, cancer cells can escape cellular ferroptosis by activating or remodeling various signaling pathways, including oxidative stress pathways, thereby limiting the efficacy of ferroptosis-activating targeted therapy. The key anti-oxidative transcription factor, nuclear factor E2 related factor 2 (Nrf2 or NFE2L2), plays a dominant role in defense machinery by reprogramming the iron, intermediate, and glutathione peroxidase 4 (GPX4)-related network and the antioxidant system to attenuate ferroptosis. In this review, we summarize the recent advances in the regulation and function of Nrf2 signaling in ferroptosis-activated cancer therapy and explore the prospect of combining Nrf2 inhibitors and ferroptosis inducers as a promising cancer treatment strategy.

Deep Learning for the Accurate Prediction of Triggered Drug Delivery.

The need to mitigate the adverse effects of chemotherapy has driven the exploration of innovative drug delivery approaches. One emerging trend in cancer treatment is the utilization of Drug Delivery Systems (DDSs), facilitated by nanotechnology. Nanoparticles, ranging from 1 nm to 1000 nm, act as carriers for chemotherapeutic agents, enabling precise drug delivery. The triggered release of these agents is vital for advancing this novel drug delivery system. Our research investigated this multifaceted delivery capability using liposomes and metal organic frameworks as nanocarriers and utilizing all three targeting techniques: passive, active, and triggered. Liposomes are modified using targeting ligands to render them more targeted toward certain cancers. Moieties are conjugated to the surfaces of these nanocarriers to allow for their binding to receptors overexpressed on cancer cells, thus increasing the accumulation of the agent at the tumor site. A novel class of nanocarriers, namely metal organic frameworks, has emerged, showing promise in cancer treatment. Triggering techniques (both intrinsic and extrinsic) can be used to release therapeutic agents from nanoparticles, thus enhancing the efficacy of drug delivery. In this study, we develop a predictive model combining experimental measurements with deep learning techniques. The model accurately predicts drug release from liposomes and MOFs under various conditions, including low- and high-frequency ultrasound (extrinsic triggering), microwave exposure (extrinsic triggering), ultraviolet light exposure (extrinsic triggering), and different pH levels (intrinsic triggering). The deep learning-based predictions significantly outperform linear predictions, proving the utility of advanced computational methods in drug delivery. Our findings demonstrate the potential of these nanocarriers and highlight the efficacy of deep learning models in predicting drug release behavior, paving the way for enhanced cancer treatment strategies.

A pH-triggered N-oxide polyzwitterionic nano-drug loaded system for the anti-tumor immunity activation research

Triple negative breast cancer (TNBC) has the characteristics of low immune cell infiltration, high expression of tumor programmed death ligand 1 (PD-L1), and abundant cancer stem cells. Systemic toxicity of traditional chemotherapy drugs due to poor drug selectivity, and chemotherapy failure due to tumor drug resistance and other problems, so it is particularly important to find new cancer treatment strategies for TNBC with limited treatment options. Both the anti-tumor natural drugs curcumin and ginsenoside Rg3 can exert anti-tumor effects by inducing immunogenic cell death (ICD) of tumor cells, reducing PD-L1 expression, and reducing cancer stem cells. However, they have the disadvantages of poor water solubility, low bioavailability, and weak anti-tumor effect of single agents. We used vinyl ether bonds to link curcumin (Cur) with N-O type zwitterionic polymers and at the same time encapsulated ginsenoside Rg3 to obtain hyperbranched zwitterionic drug-loaded micelles OPDEA-PGED-5HA@Cur@Rg3 (PPH@CR) with pH response. In vitro cell experiments and in vivo animal experiments have proved that PPH@CR could not only promote the maturation of dendritic cells (DCs) and increase the CD4+ T cells and CD8+ T cells by inducing ICD in tumor cells but also reduce the expression of PD-L1 in tumor tissues, and reduce cancer stem cells and showed better anti-tumor effects and good biological safety compared with free double drugs, which is a promising cancer treatment strategy.

Relationship of pancreatitis to pancreatic cancer: from population-based observations to preclinical and mechanistic insights

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest malignancies, accounting for 95% of pancreatic cancer cases, with a 5-year survival rate of around 10%. The relationship between pancreatitis and pancreatic cancer has been noted within the medical community. Recent epidemiological data and findings from experimental mouse models have underscored pancreatitis as a critical risk factor for pancreatic cancer. Therefore, exploring the mechanisms underlying the transition from pancreatitis to pancreatic cancer is crucial for improving early detection and treatment strategies for pancreatic cancer. In this review, we conducted a comprehensive search of the PubMed database and discussed relevant original studies, focusing on three key areas: findings from population- and animal-based studies, the role of pancreatic epithelial cell-intrinsic factors, and the impact of immune cells and cytokines. Additionally, we offered our prospectives on possible future research directions.

Applications of Modified Mesenchymal Stem Cells as Targeted Systems against Tumor Cells

Combined gene and cell therapy are promising strategies for cancer treatment. Given the complexity of cancer, several approaches are actively studied to fight this disease. Using mesenchymal stem cells (MSCs) has demonstrated dual antitumor and protumor effects as they exert massive immune/regulatory effects on the tissue microenvironment. MSCs have been widely investigated to exploit their antitumor target delivery system. They can be genetically modified to overexpress genes and selectively or more efficiently eliminate tumor cells. Current approaches tend to produce more effective and safer therapies using MSCs or derivatives; however, the effect achieved by engineered MSCs in solid tumors is still limited and depends on several factors such as the cell source, transgene, and tumor target. This review describes the progress of gene and cell therapy focused on MSCs as a cornerstone against solid tumors, addressing the different MSC-engineering methods that have been approached over decades of research. Furthermore, we summarize the main objectives of engineered MSCs against the most common cancers and discuss the challenges, limitations, risks, and advantages of targeted treatments combined with conventional ones.

NIR-II-Responsive Versatile Nanozyme Based on H2O2 Cycling and Disrupting Cellular Redox Homeostasis for Enhanced Synergistic Cancer Therapy.

Disturbing cellular redox homeostasis within malignant cells, particularly improving reactive oxygen species (ROS), is one of the effective strategies for cancer therapy. The ROS generation based on nanozymes presents a promising strategy for cancer treatment. However, the therapeutic efficacy is limited due to the insufficient catalytic activity of nanozymes or their high dependence on hydrogen peroxide (H2O2) or oxygen. Herein, we reported a nanozyme (CSA) based on well-defined CuSe hollow nanocubes (CS) uniformly covered with Ag nanoparticles (AgNPs) to disturb cellular redox homeostasis and catalyze a cascade of intracellular biochemical reactions to produce ROS for the synergistic therapy of breast cancer. In this system, CSA could interact with the thioredoxin reductase (TrxR) and deplete the tumor microenvironment-activated glutathione (GSH), disrupting the cellular antioxidant defense system and augmenting ROS generation. Besides, CSA possessed high peroxidase-mimicking activity toward H2O2, leading to the generation of various ROS including hydroxyl radical (•OH), superoxide radicals (•O2-), and singlet oxygen (1O2), facilitated by the Cu(II)/Cu(I) redox and H2O2 cycling, and plentiful catalytically active metal sites. Additionally, due to the absorption and charge separation performance of AgNPs, the CSA exhibited excellent photothermal performance in the second near-infrared (NIR-II, 1064 nm) region and enhanced the photocatalytic ROS level in cancer cells. Owing to the inhibition of TrxR activity, GSH depletion, high peroxidase-mimicking activity of CSA, and abundant ROS generation, CSA displays remarkable and specific inhibition of tumor growth.

HES6 Mediates Oxidative Phosphorylation Pathway to Promote Immune Infiltration of CD8+ T Cells in Lung Adenocarcinoma.

Tumor immunotherapy has recently gained popularity as a cancer treatment strategy. The molecular mechanism controlling immune infiltration in lung adenocarcinoma (LUAD) cells, however, is not well characterized. Investigating the immune infiltration modulation mechanism in LUAD is crucial. LUAD patient samples were collected, and HES6 expression and immune infiltration level of CD8+ T cells in patient tissues were analyzed. Bioinformatics was utilized to identify binding relationship between E2F1 and HES6, and enrichment pathway of HES6. The binding of E2F1 to HES6 was verified using dual-luciferase and ChIP experiments. HES6 and E2F1 expression in LUAD cells was detected. LUAD cells were co-cultured with CD8+ T cells, and the CD8+ T cell killing level, IFN-γ secretion, and CD8+ T-cell chemotaxis level were measured. Expression of key genes involved in oxidative phosphorylation was detected, and the oxygen consumption rate of LUAD cells was assessed. A mouse model was constructed to assay Ki67 expression and apoptosis in tumor tissue. High expression of HES6 promoted CD8+ T-cell infiltration and enhanced T-cell killing ability through oxidative phosphorylation. Further bioinformatics analysis, molecular experiments, and cell experiments verified that E2F1 negatively regulated HES6 by oxidative phosphorylation, which suppressed CD8+ T-cell immune infiltration. In addition, in vivo assays illustrated that silencing HES6 repressed tumor cell immune evasion. E2F1 inhibited HES6 transcription, thereby mediating oxidative phosphorylation to suppress immune infiltration of CD8+ T cells in LUAD. The biological functions and signaling pathways of these genes were analyzed, which may help to understand the possible mechanisms regulating immune infiltration in LUAD.

The Potential Role of Non-coding RNAs in Regulating Ferroptosis in Cancer: Mechanisms and Application Prospects.

Cancer is the second leading cause of death globally. Despite some successes, conventional cancer treatments are insufficient to address the growing problem of drug resistance in tumors and to achieve efficient treatment outcomes. Therefore, there is an urgent need to explore new therapeutic options. Ferroptosis, a type of iron- and reactive oxygen species-dependent regulated cell death, has been closely associated with cancer development and progression. Non-coding RNAs (ncRNAs) are a class of RNAs that do not code for proteins, and studies have demonstrated their involvement in the regulation of ferroptosis in cancer. This review aims to explore the molecular regulatory mechanisms of ncRNAs involved in ferroptosis in cancer and to emphasize the feasibility of ferroptosis and ncRNAs as novel therapeutic strategies for cancer. We conducted a systematic and extensive literature review using PubMed, Google Scholar, Web of Science, and various other sources to identify relevant studies on ferroptosis, ncRNAs, and cancer. A deeper understanding of ferroptosis and ncRNAs could facilitate the development of new cancer treatment strategies.

Testosterone Nanoemulsion Prevents Prostate Cancer: PC-3 and LNCaP Cell Viability In Vitro

For many years, it has been speculated that elevated testosterone levels may be critically involved in the genesis and proliferation of prostate cancer. Methods: The effect of testosterone on the metabolic activity of hormone-independent [PC-3] and hormone-dependent [LNCAP] cancer cells was investigated in vitro. Additionally, the impact of testosterone nanoemulsion [nanocare®] on cell viability was accessed by flow cytometry. Results: Despite the dependency of the normal prostate and of most prostatic cancers upon androgens, the obtained results indicate that, contrary to prevailing opinion, the supplementation of testosterone with higher doses in nanoemulsion was able to lower the metabolic activity and viability of prostate cancer cells. Conclusions: We conclude that the growth of hormone-independent and hormone-dependent prostate cancer cells was reduced by the exposure of a nanoemulsion of bioidentical testostosterone in vitro. To the best of our knowledge, this is the first time that the potential effect of a testosterone nanoemulsion on the metabolic activity of prostate cancer cells has been shown. Such tests suggest that the growth of hormone-independent and hormone-dependent prostate cancer cells was reduced by the administration of bioidentical testostosterone, and this might be an interesting strategy for prostate cancer treatment in diagnosed patients.

Ferroptosis crosstalk in anti-tumor immunotherapy: molecular mechanisms, tumor microenvironment, application prospects.

Immunotherapies for cancer, specifically immune checkpoint inhibition (ICI), have shown potential in reactivating the body's immune response against tumors. However, there are challenges to overcome in addressing drug resistance and improving the effectiveness of these treatments. Recent research has highlighted the relationship between ferroptosis and the immune system within immune cells and the tumor microenvironment (TME), suggesting that combining targeted ferroptosis with immunotherapy could enhance anti-tumor effects. This review explores the potential of using immunotherapy to target ferroptosis either alone or in conjunction with other therapies like immune checkpoint blockade (ICB) therapy, radiotherapy, and nanomedicine synergistic treatments. It also delves into the roles of different immune cell types in promoting anti-tumor immune responses through ferroptosis. Together, these findings provide a comprehensive understanding of synergistic immunotherapy focused on ferroptosis and offer innovative strategies for cancer treatment.