Strategy For Cancer Treatment Research Articles

Causal relationship between gut microbiota and lung squamous cell carcinoma: a bidirectional two-sample Mendelian randomization study.

This study aims to explore the potential causal relationship between gut microbiota and lung squamous cell carcinoma (LUSC). A bidirectional two-sample Mendelian randomization analysis was conducted using genome-wide association study (GWAS) data from gut microbiota and LUSC. Gut microbiota served as the exposure factor, with instrumental variables selected from a GWAS involving 18 340 participants. LUSC data were drawn from a European cohort including 29 266 LUSC cases and 56 450 controls. Inverse-variance weighted (IVW) method was used as the primary method, with the Benjamini-Hochberg method applied to adjust for multiple comparisons. An independent dataset (ieu-a-967, containing 3275 LUSC cases and 15 038 controls) was used for replication analysis to ensure robustness. IVW analysis found that Butyricicoccus (OR = 0.79, 95% CI: 0.63-0.99, P = .042) and Coprobacter (OR = 0.85, 95% CI: 0.74-0.97, P = .018) were significantly protective against LUSC. In contrast, Victivallis (OR = 1.11, 95% CI: 1.00-1.23, P = .045) and Ruminococcus (OR = 1.28, 95% CI: 1.03-1.60, P = .028) increased LUSC risk. Replication analysis in the independent dataset confirmed significant associations for Ruminococcus and Coprobacter. No reverse causality or pleiotropy was detected. This study provides evidence of a causal relationship between specific gut microbiota and LUSC risk, highlighting new microbial targets for potential prevention and treatment strategies in lung cancer. Key messages What is already known on this topic? Previous studies have suggested potential links between gut microbiota composition and the development of various cancers, including lung cancer. However, the exact causal relationship between specific gut microbiota and lung squamous cell carcinoma (LUSC) has remained unclear. Traditional observational studies have struggled to determine the direction of causality due to confounding factors, making further investigation necessary through more robust methods such as Mendelian randomization (MR). What this study adds? This bidirectional MR study provides novel genetic evidence indicating that certain gut microbiotas are causally associated with LUSC risk. Specifically, Butyricicoccus appears to reduce the risk of LUSC, while Victivallis increases the risk. These findings highlight the role of the gut-lung axis in LUSC and open up new avenues for exploring gut microbiota as potential modulators of lung cancer risk. How this study might affect research, practice, or policy? The implications of this study may significantly influence future research into cancer prevention strategies by targeting gut microbiota. Additionally, it could inform clinical practices aimed at modulating gut microbiota to lower the risk of LUSC, potentially influencing dietary or probiotic interventions to reduce cancer susceptibility. Furthermore, these results might shape public health policies that focus on the gut-lung axis as a novel avenue for cancer prevention and management.

Supporting equitable cervical cancer elimination for Australia's culturally and linguistically diverse communities: A call for intersectoral action.

Cervical cancer is a preventable disease and is related to persistent health equities. Whilst several priority populations face health inequities related to cervical cancer prevention, my co-authors and I bring special attention to those who identify as culturally and linguistically diverse (CALD). By reflecting on some of our research and work experiences, we propose four ways that governments and policymakers can enact the community engagement goals of the published and proposed cervical cancer prevention and treatment strategies for CALD communities. This includes: (1) Developing a culturally appropriate approach to collecting and interpreting cultural, ethnic and linguistic data; (2) Building and adapting the effective multicultural community policies and partnerships developed during COVID-19; (3) Incorporating national strategy recommendations across all relevant government policies and (4) Sustainably resourcing and supporting participatory health promotion activities and interventions. By implementing the recommendations above, Australia will continue to lead the elimination of cervical cancer as a public health problem. It will demonstrate how genuine and authentic CALD partnerships and collaborations can reduce national CALD health inequities.

Research progress of immune checkpoint inhibitors in ovarian cancer

Ovarian cancer is the deadliest malignant tumor in the female reproductive system. Despite advancements in standard treatments such as tumor debulking surgery and platinum-based chemotherapy, the overall survival rate remains low. The emergence of targeted therapies, including Poly(ADP-ribose) polymerase (PARP) inhibitors and anti-angiogenic agents, has provided new avenues for treatment. However, drug resistance and disease heterogeneity continue to pose significant challenges. Immune checkpoint inhibitors (ICIs), as an emerging therapeutic approach, primarily target the programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) and cytotoxic T-lymphocyte antigen 4 (CTLA-4) pathways to restore anti-tumor immune responses. Although ICIs have shown significant efficacy in other malignancies, their effectiveness in ovarian cancer is limited, with a response rate of only 10–15% for monotherapy. Recent studies have focused on combining ICIs with chemotherapy, anti-angiogenic agents, or PARP inhibitors to enhance therapeutic outcomes. This article reviews the progress of ICIs in ovarian cancer, including monotherapy and combination treatment strategies, and explores emerging therapeutic targets and strategies aimed at improving patient prognosis and achieving personalized treatment. By gaining a deeper understanding of the tumor microenvironment and its immune evasion mechanisms, there is hope for developing more effective treatment options in the future, ultimately improving the survival rates and quality of life for ovarian cancer patients.

NIR-715 photodynamic therapy induces immunogenic cancer cell death by enhancing the endoplasmic reticulum stress response

Effectively interfering with endoplasmic reticulum (ER) function in tumor cells and simultaneously activating an anti-tumor immune microenvironment to attack the tumor cells are promising strategies for cancer treatment. However, precise ER-stress induction is still a huge challenge. In this study, we synthesized a near-infrared (NIR) probe, NIR-715, which induces tumor cell death and inhibits tumor growth without causing apparent side effects. NIR-715 triggers severe ER stress and immunogenic cell death (ICD) after visible light exposure. NIR-715 induced ICD-associated HMGB1 release in vitro and anti-tumor immune responses, including increased cytotoxic T lymphocyte (GZMB+ CD8+ T cell) infiltration and decreased numbers of exhausted T lymphocytes (PD-L1+ CD8+ T cell). These findings suggest that NIR-715 may be a novel agent for “cold” tumor photodynamic therapy (PDT).Schematic illustration of NIR-715 photodynamic therapy for visible light-triggered, endoplasmic reticulum-targeting antitumor therapy.

Circulating microRNAs as a Prognostic Tool to Determine Treatment Efficacy in Lung Cancer Patients Undergoing Pembrolizumab PD-1 Blockade Immunotherapy

Background: Pembrolizumab has recently emerged as a PD-1 blockade immunotherapy treatment for lung cancer. It is critical that such treatment strategies for lung cancer should be chosen not only on the basis of histopathological features and the expression of targetable cell surface proteins (such as PD-1), but should rather be selected based on other determinants of treatment success or risk factors for poor prognosis. One method to forecast cancer trajectory is the identification of biomolecular signatures such as microRNAs (miRNAs), non-protein-coding RNA molecules that play a regulatory role in gene expression by modulating the translation or stability of messenger RNA. Methods: To find out which miRNAs have an important influence on anti-PD-1 treatment outcomes, we evaluated miRNA levels in sera from 38 lung cancer patients undergoing 3 months of pembrolizumab treatment. We selected a panel of miRNAs previously shown to be involved in lung cancer or PD-1 signaling and performed qPCR analysis. Results: Overall, we observed a significant decrease in the levels of miR126-5p (4-fold), let-7a (5-fold), miR133a-3p (4-fold), miR3615 (2-fold), miR4516 (3-fold), miR16 (3-fold), miR34c-5p (2-fold), miR20b-5p (5-fold), miR106b-5p (5-fold), miR146a-5p (3-fold) and miR181b-5p (3-fold) in response to treatment indicating effectiveness of immunotherapy. Within our selected panel of miRNAs, we identified two markers relevant to cancer prognosis: miR-217, which is negatively associated with patient survival, and let-7a, which is positively associated with patient survival. Conclusions: Our findings suggest that circulating miRNAs can be used for future treatment evaluation and lung cancer prognosis, with potential as therapeutic targets.

Nanozyme as Tumor Energy Homeostasis Disruptor to Augment Cascade Catalytic Therapy.

Breaking the balance of the tumor microenvironment and reshaping it sustainably remain major challenges in lung cancer treatment. Here, a "tumor energy homeostasis disruptor", the Cu2O@Au nanozyme was developed, which exhibits excellent glucose oxidase-like activity, enabling it to be used for starvation therapy and as a mimic peroxidase for chemodynamic therapy (CDT), producing •OH. Cu2O@Au nanozymes consume glucose at the tumor site to block the tumor's energy supply, produce H2O2 continuously, and lower the pH to enhance the efficiency of CDT, initiating a cascade reaction that leads to a storm of reactive oxygen species (ROS). Furthermore, Cu2O@Au nanozyme consumes glutathione and reduces the expression of the SLC7A11 (xCT) protein to decrease cancer cell uptake of cysteine, further enhancing the burst of ROS, resulting in lipid peroxidation in tumor cells and ultimately leading to ferroptosis. The excellent photothermal performance of Cu2O@Au can further enhance CDT. Additionally, Cu2O@Au nanozyme also has computed tomography (CT) and photothermal imaging capabilities. In conclusion, Cu2O@Au nanozymes, acting as tumor energy homeostasis disruptor, can effectively inhibit tumor growth and successfully achieve the synergistic effects of starvation therapy/CDT/photothermal therapy (PTT). This multifunctional nanozyme holds promise for providing valuable insights and therapeutic strategies for cancer treatment.

Prooxidant state in anticancer drugs and prospect use of mitochondrial cofactors and anti-inflammatory agents in cancer prevention.

An extensive body of literature has associated cancer with redox imbalance and inflammatory conditions. Thus, several studies and current clinical practice have relied on the use of anticancer drugs known to be associated with prooxidant state. On the other hand, a number of studies have reported on the effects of several antioxidants, anti-inflammatory agents and of mitochondrial cofactors (also termed mitochondrial nutrients, MNs) in counteracting or slowing carcinogenesis, or in controlling cancer growth. In the available literature, a body of evidence points on the roles of anti-inflammatory agents and of individual MNs against carcinogenesis or in controlling cancer cell proliferation, but only a few reports on the combined use of two or the effect of three MNs. These combinations are proposed as potentially successful tools to counteract carcinogenesis in prospective animal model studies or in adjuvant cancer treatment strategies. A "triad" of MNs are suggested to restore redox balance, mitigate side effects of prooxidative anticancer drugs, or aid in cancer prevention and/or adjuvant therapy. By elucidating their mechanistic underpinnings and appraising their clinical efficacy, we aim to contribute with a comprehensive understanding of these therapeutic modalities.

Coupling Probiotics with CaO2 Nanoparticle-Loaded CoFeCe-LDH Nanosheets to Remodel the Tumor Microenvironment for Precise Chemodynamic Therapy.

Chemodynamic therapy (CDT) has become an emerging cancer treatment strategy with advantages of tumor-specificity, high selectivity, and low systemic toxicity. However, it usually suffers from low therapeutic efficacy. This is caused by low hydroxyl radical (·OH) yield arising because of the relatively high pH, overexpressed glutathione, and low H2O2 concentration in the tumor microenvironment (TME). Herein, a probiotic metabolism-initiated pH reduction and H2O2 supply-enhanced CDT strategy is reported to eradicate tumors by generating ·OH, in which Lactobacillus acidophilus is coupled with CoFeCe-layered double hydroxide nanosheets loaded with CaO2 nanoparticles (NPs) as a chemodynamic platform for high-efficiency CDT (CaO2/LDH@L. acidophilus). Owing to the hypoxia tropism of L. acidophilus, CaO2/LDH@L. acidophilus exhibits increased accumulation at tumor sites compared with the CaO2/LDH. The CaO2 NPs loaded on CoFeCe-LDH nanosheets are decomposed into H2O2 in the TME. L. acidophilus metabolite-induced pH reduction (<5.5) and CaO2-mediated in situ H2O2 generation synergistically boost ·OH generation activity of the CoFeCe-LDH nanosheets, effectively damaging cancer cells and ablating tumors with a tumor inhibition rate of 96.4%, 2.32-fold higher than that of CaO2/LDH. This work demonstrates that probiotics can function as a tumor-targeting platform to remodel the TME and amplify ROS generation for highly efficient and precise CDT.

Beginning at the ends: telomere and telomere-based cancer therapeutics.

Telomeres, which are situated at the terminal ends of chromosomes, undergo a reduction in length with each cellular division, ultimately reaching a critical threshold that triggers cellular senescence. Cancer cells circumvent this senescence by utilizing telomere maintenance mechanisms (TMMs) that grant them a form of immortality. These mechanisms can be categorized into two primary processes: the reactivation of telomerase reverse transcriptase and the alternative lengthening of telomeres (ALT) pathway, which is dependent on homologous recombination (HR). Various strategies have been developed to inhibit telomerase activation in 85-95% of cancers, including the use of antisense oligonucleotides such as small interfering RNAs and endogenous microRNAs, agents that simulate telomere uncapping, expression modulators, immunotherapeutic vaccines targeting telomerase, reverse transcriptase inhibitors, stabilization of G-quadruplex structures, and gene therapy approaches. Conversely, in the remaining 5-15% of human cancers that rely on ALT, mechanisms involve modifications in the chromatin environment surrounding telomeres, upregulation of TERRA long non-coding RNA, enhanced activation of the ataxia telangiectasia and Rad-3-related protein kinase signaling pathway, increased interactions with nuclear receptors, telomere repositioning driven by HR, and recombination events between non-sister chromatids, all of which present potential targets for therapeutic intervention. Additionally, combinatorial therapy has emerged as a strategy that employs selective agents to simultaneously target both telomerase and ALT, aiming for optimal clinical outcomes. Given the critical role of anti-TMM strategies in cancer treatment, this review provides an overview of the latest insights into the structure and function of telomeres, their involvement in tumorigenesis, and the advancements in TMM-based cancer therapies.

SOCS1: A potential diagnostic and prognostic marker for aggressive gliomas and a new target for immunotherapy.

Gliomas, the most common and deadly cancers of the central nervous system, present a unique immunological barrier that severely undermines the effectiveness of immunotherapies. Suppressor of cytokine signaling 1 (SOCS1), belonging to the SOCS protein family and playing a pivotal role in various cancer treatment strategies and is abundant in high-grade gliomas. This study conducted a comparative analysis of SOCS1 and glioma immune checkpoints. It underscores the feasibility of leveraging SOCS1 as a promising diagnostic and prognostic marker for aggressive gliomas, thus offering novel targets for glioma immunotherapy. Comprehensive gene expression analyses and clinical data validations were performed across multiple databases. The expression and biological functions of SOCS1 were examined through an array of techniques including pan-cancer analysis, functional enrichment, gene set variation analysis, and immune microenvironment examination. This was done alongside a comparison of the similarities between SOCS1 and various glioma immune checkpoints. Utilizing clinical information from patients, a bespoke predictive model was developed to further corroborate the prognostic capabilities of SOCS1. The investigation revealed considerable similarities between SOCS1 and several immune checkpoints such as CTLA4, demonstrating SOCS1's role as an independent prognostic factor positively influencing glioma patient outcomes. The inclusion of SOCS1 in the developed predictive model significantly enhanced its precision. Our findings highlight SOCS1's potential as an innovative target for glioma immunotherapy, providing a novel strategy to overcome the immunological barriers posed by gliomas. Furthermore, identifying SOCS1 as a viable diagnostic marker for aggressive gliomas improves the accuracy of prognostic predictions for affected patients.

Targeting Nudix Hydrolase 5 with Bioactive Flavonoids: Molecular Dynamics and Docking Studies for Breast Cancer Therapy.

Breast cancer (BC) is the most prevalent malignancy among women globally and the leading cause of cancer-related mortality. Consequently, there is an urgent need for new, effective treatment strategies for breast cancer. Research has shown that the enzyme nudix hydrolase 5 (NUDT5) plays a critical role in promoting breast cancer aggressiveness and serves as a key regulator of oncogenic pathways. The development of NUDT5 inhibitors presents a viable strategy for enhancing treatment results in managing BC. The ability of the flavonoids to modulate key biochemical pathways and improve therapeutic outcomes highlights their promise in developing novel breast cancer treatments. Hence, the main objective of the present investigation is to identify the potential interaction of structurally diverse bioactive flavonoids with the active site of the target NUDT5. Our docking analysis revealed that the flavonoids such as naringin and genistein have shown a significant binding association with residues Arg51, Asp60, Gln82, Arg84, Ala96, Leu98, Glu112, Glu116, Met132, Cys139, Ile141, and Glu166 of NUDT5, suggesting its potential as a potent inhibitor. The stabilizing effects of these leads (naringin and genistein) were further validated using molecular dynamics investigations, including RMSD, RMRF, Rg, SASA, PCA, and FEL. The results of the MD simulation studies evidenced a more significant interaction between genistein and NUDT5, indicating a steady and robust affinity, making genistein a more promising inhibitor. In conclusion, the flavonoid genistein has a strong potential as a therapeutic agent for targeting NUDT5 in breast cancer treatment making it viable candidates for further preclinical and clinical investigations.

Trace element zinc metabolism and its relation to tumors

Zinc is an essential trace element in the human body, playing a crucial role in cellular metabolism.Dysregulation of zinc homeostasis can lead to abnormal cellular metabolism, contributing to diseases and closely related to tumor development. Adequate zinc intake can maintain zinc homeostasis in the body and support normal cellular metabolism. This review discusses the metabolic processes of zinc in the human body and its close relationship with tumorigenesis. It briefly describes zinc absorption, transport, storage, and release, as well as its important role in gene expression, signal transduction, oxidative stress, immune response, and apoptosis. It focuses on the abnormal cellular metabolism caused by excessive or insufficient zinc, the relationship between zinc homeostasis disruption and metabolic syndrome, and the mechanisms involved in tumor development. It analyzes how changes in the expression and activity of zinc transporters may lead to disrupted zinc homeostasis in tumor tissues. It points out that zinc deficiency is associated with various cancers, including prostate cancer, hepatocellular carcinoma, pancreatic cancer, lung cancer, ovarian cancer, esophageal squamous cell carcinoma, and breast cancer. The summary emphasizes that zinc metalloproteins could serve as potential targets for cancer therapy, and regulating the expression and activity of zinc transport proteins may offer new methods and strategies for clinical cancer treatment.

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Iron Oxide Nanoparticles Functionalized with Macrocycle Antagonists for CXCR4 Receptor Targeting in Cancer Cells

Iron oxide nanoparticles (IONPs) have shown great promise in targeted cancer therapy due to their unique magnetic properties and ability to be functionalized with various ligands. This study explores the use of iron oxide nanoparticles (IONPs) functionalized with macrocycle antagonists to target CXCR4 receptors on cancer cells. The synthesis of superparamagnetic iron oxide nanoparticles (SPIONs) was validated through XRD and TEM analyses, which showed uniform, roughly spherical particles. Fluorescence-loaded SPIONs provided enhanced imaging contrast in Jurkat cancer cells. Flow cytometry demonstrated that the nanoparticles effectively blocked CXCR4 receptors, highlighting their potential for targeted cancer therapy. These findings underscore the successful synthesis, characterization, and functionalization of SPIONs, paving the way for advanced nanomedicine strategies in cancer diagnostics and treatment.

Enhancing Magnetic Hyperthermia Efficiency in Pd/Fe-Oxide Hybrid Nanoparticles through Mn-Doping.

Multifunctional, biocompatible magnetic materials, such as iron oxide nanoparticles (IONPs), hold great potential for biomedical applications including diagnostics (e.g., MRI) and cancer therapy. In particular, they can play a crucial role in advancing cancer thermotherapy by generating heat when administered intratumorally and when exposed to an alternating magnetic field. This heat application is often combined with radio- (chemo)therapy and/or imaging. Consequently, the design of materials for such a multimodal approach requires hybrid nanoparticles that retain their magnetic properties while integrating additional functionalities. This work introduces synthesis and investigation of magnetically enhanced nanoparticles with a palladium core (envisioned for future radiolabeling with therapeutic 103Pd) and a magnetic iron oxide shell containing paramagnetic manganese (Pd/Fe|(nMn)-oxide, n = 0.25 and 0.5). Doping the iron oxide lattice with Mn significantly increases magnetic saturation, boosting specific loss power up to 1.7 times compared to that of undoped analogs. Interestingly, higher Mn-content in Pd/Fe|(0.5Mn)-oxide leads to a pronounced Mn outer rim, enhancing the heating efficiency at 346 kHz and 23 mT and contributing to the water exchange on the surface of the paramagnetically doped nanoparticles, resulting in additional T 1 MRI contrast. The enhanced magnetic properties of the hybrid Pd/Fe|Mn-oxide nanoparticles enable effective therapeutic outcomes with injection of only small quantities of the material, offering great potential for effective cancer treatment strategies that combine hyperthermia/thermal ablation with radiotherapy while allowing for real-time monitoring via MRI.

The N6-methyladenosine writer METTL3 promotes breast cancer progression through YTHDF2-dependent posttranscriptional silencing of GSDMD.

Cell pyroptosis is a form of programmed cell death, with Gasdermin-D (GSDMD) acting as its key executor. While activating pyroptosis represents a promising therapeutic strategy for cancer, the regulatory mechanisms governing GSDMD expression during cell death remain poorly understood. In this study, we identified METTL3 as a negative regulator of GSDMD-mediated pyroptosis, with high expression in breast cancer (BC) cells. YTHDF2 was found to recognize the m6A modification of GSDMD, thereby decreasing its stability. Finally, in vivo experiments further demonstrated the inhibitory effect of the METTL3 inhibitor STM2457 on tumors. Overall, these findings suggest that inhibition of METTL3 can enhance GSDMD-mediated pyroptosis and reveal a novel regulatory mechanism governing GSDMD expression, presenting a novel strategy for cancer treatment.

Development and validation of the Normalized Organoid Growth Rate (NOGR) metric in brightfield imaging-based assays

This study focuses on refining growth-rate-based drug response metrics for patient-derived tumor organoid screening using brightfield live-cell imaging. Traditional metrics like Normalized Growth Rate Inhibition (GR) and Normalized Drug Response (NDR) have been used to assess organoid responses to anticancer treatments but face limitations in accurately quantifying cytostatic and cytotoxic effects across varying growth rates. Here, we introduce the Normalized Organoid Growth Rate (NOGR) metric, specifically developed for brightfield imaging-based assays. A label-free image analysis model was applied to segment organoids precisely, track their growth rates over time, and classify viable and dead organoids. Testing eleven phenotypically distinct pancreatic cancer organoid models with five chemotherapeutics demonstrates that the NOGR metric more effectively captures cytostatic and cytotoxic drug effects compared to existing methods. This approach enhances the biological relevance of drug sensitivity assessments on organoids and offers a valuable tool for advancing personalized cancer treatment strategies.

A stearate-rich diet and oleate restriction directly inhibit tumor growth via the unfolded protein response.

Fatty acids are known to have significant effects on the properties of cancer cells. Therefore, these compounds have been incorporated into therapeutic strategies. However, few studies have examined the effects of individual fatty acids and their interactions in depth. This study analyzed the effects of various fatty acids on cancer cells and revealed that stearic acid, an abundant saturated fatty acid, had a stronger inhibitory effect on cell growth than did palmitic acid, which is also an abundant saturated fatty acid, by inducing DNA damage and apoptosis through the unfolded protein response (UPR) pathway. Intriguingly, the negative effects of stearate were reduced by the presence of oleate, a different type of abundant fatty acid. We combined a stearate-rich diet with the inhibition of stearoyl-CoA desaturase-1 to explore the impact of diet on tumor growth. This intervention significantly reduced tumor growth in both ovarian cancer models and patient-derived xenografts (PDXs), including those with chemotherapy resistance, notably by increasing stearate levels while reducing oleate levels within the tumors. Conversely, the negative effects of a stearate-rich diet were mitigated by an oleate-rich diet. This study revealed that dietary stearate can directly inhibit tumor growth through mechanisms involving DNA damage and apoptosis mediated by the UPR pathway. These results suggest that dietary interventions, which increase stearic acid levels while decreasing oleic acid levels, may be promising therapeutic strategies for cancer treatment. These results could lead to the development of new cancer treatment strategies.

Thiazolidinedione derivatives in cancer therapy: exploring novel mechanisms, therapeutic potentials, and future horizons in oncology.

Thiazolidinedione derivatives have shown significant potential as targeted cancer therapies by leveraging their various mechanisms of action. These include suppressing cell proliferation, triggering apoptosis, and influencing signaling pathways associated with tumor development. Their multifaceted effects make them promising candidates for advancing cancer treatment strategies. They have shown significant promise as anti-cancer agents, particularly through their ability to inhibit lipogenesis pathways and apoptosis essential for cancer cell survival and proliferation. This review comprehensively examines the anti-cancer potential of thiazolidinedione derivatives by targeting key aspects of lipid metabolism, apoptosis, and various mechanistic pathways. This review provides an in-depth examination of the anti-cancer potential of TZD derivatives, focusing on their mechanisms of action, therapeutic applications, and future directions in oncology. The anti-tumor effects of TZDs primarily involve the stimulation of peroxisome proliferator-activated receptor gamma (PPAR-γ), suppressing cell proliferation, induction of apoptosis, and inhibition of angiogenesis. Moreover, recent evidence highlights their ability to modulate non-PPAR-γ pathways, such as PI3K/Akt, NF-κB, and MAPK, further expanding their role in overcoming drug resistance and enhancing therapeutic outcomes. This review explores the preclinical (in vitro and in vivo) and clinical research investigating TZD derivatives efficacy in various cancer types. The insights underscore the significance of targeting lipogenesis as a novel anti-cancer strategy, positioning thiazolidinedione derivatives as potent candidates for future cancer therapeutics. As the oncology landscape evolves, TZD derivatives (rosiglitazone, pioglitazone, inolitazone, troglitazone, and 2,4-thiazolidinedione derivatives) represent a promising class of agents with the potential to contribute meaningfully to cancer treatment. By integrating existing knowledge with recent advancements, this study provides valuable insights into the role of thiazolidinedione derivatives in cancer treatment, paving the way for further research and clinical applications.