INTRODUCTION:Targeted cancer therapy focuses on inhibiting specific molecular pathways that drive tumor growth and survival. In this study, computational methods were employed to identify potential acetogenin- based inhibitors of two key anti-apoptotic proteins, HER2 and MELK. Given their crucial involvement in cancer pathogenesis, HER2 and MELK have emerged as significant molecular targets for the development of effective cancer therapies. Acetogenins, a class of bioactive compounds exclusive to the Annonaceae family, have attracted significant attention for their anticancer properties. METHODS:A library of 47 acetogenins derived from Annona muricata and Annona squamosa was screened using molecular docking, and the top-scoring ligand-protein complexes were further evaluated through 100 ns molecular dynamics (MD) simulations. RESULTS:Docking results identified squamocin-C and annocherin as the top-scoring potential binders for HER2 and MELK, respectively, that exhibited predicted binding energies ranging from -171.43 to -133.50 kcal/mol in docking studies and favorable interaction profiles with key active-site residues. MD simulations revealed that the annocherin-MELK complex maintained greater structural stability and lower root mean square deviation (RMSD) fluctuations compared to the squamocin-C-HER2 complex, suggesting enhanced conformational retention. Collectively, RMSF, radius of gyration, and hydrogen bond occupancy data suggest thermodynamic stability of the respective complexes. ADME and toxicity predictions indicated that annocherin possessed higher solubility and permeability, while squamocin-C exhibited greater blood-brain barrier permeability. CONCLUSION:Overall, this study highlights acetogenins as promising scaffolds for the rational design of novel MELK and HER2 inhibitors, offering a potential route toward targeted cancer therapeutics derived from natural products.
INTRODUCTION:Cancer remains a leading contributor to global mortality, and current therapeutic interventions continue to grapple with significant limitations. The multi-target characteristics and low toxicity of natural products position them as promising sources of novel anti-tumor agents. Isorhamnetin (ISO), a naturally occurring O-methylated flavonol, exemplifies this potential, demonstrating diverse bioactivities such as cardiovascular protection, inflammation modulation, and cancer suppression. METHOD:This review systematically analyzed the latest advances in ISO mediated anti-tumor effects by searching databases such as PubMed and Web of Science, focusing on elucidating their molecular mechanisms, experimental evidence, and combination therapy strategies. RESULT:Research has shown that ISO has broad-spectrum anti-tumor activity against various malignant tumors. Mechanistically, ISO inhibits tumor cell proliferation, induces apoptosis, suppresses angiogenesis, and metastasis by regulating key signaling pathways. In addition, combining ISO with traditional chemotherapy drugs or autophagy inhibitors has a synergistic effect. DISCUSSION:Although the multi-target anti-tumor potential of ISO has been validated, the direct molecular targets have not been fully identified, and pharmacokinetics, metabolic pathways, and bioavailability still need to be systematically evaluated. The optimal clinical dose and long-term toxicity also need to be considered to promote translational applications. CONCLUSION:ISO is a promising natural anti-tumor drug with multi-target regulatory ability. This review provides a theoretical basis for its anti-tumor mechanism and supports its clinical translational potential as a new strategy for cancer treatment.
INTRODUCTION:Glioma is the most prevalent primary central nervous system malignancy. Wogonoside, a flavonoid bioactive derived from Scutellaria baicalensis Georgi, has been reported to induce apoptosis in glioblastoma cells. However, the functional roles and molecular mechanisms in regulating glioma stem cell (GSC)-driven malignant progression remain poorly defined. The authors initially investigated the inhibitory effects of wogonoside on GSCs, as well as the intrinsic mechanisms responsible for these actions. MATERIALS AND METHODS:In vitro functional assays including extreme limiting dilution analysis, tumorsphere formation, tube formation, flow cytometry, immunofluorescence, and Western blotting were performed in primary human GSC lines (GSC#1 and GSC#2). RNA sequencing was applied to identify the key signaling pathways modulated by wogonoside. An orthotopic glioma mouse model was established to verify the in vivo antitumor efficacy of wogonoside. RESULTS:Wogonoside significantly suppressed GSC self-renewal capacity, as evidenced by reduced tumor sphere number and size, decreased tumor-forming frequency, and downregulated the expression of GSC stemness markers SOX2 and CD133. Mechanistically, wogonoside inhibited the PI3K/AKT signaling pathway and enhanced ZEB1-mediated transcriptional repression in GSCs. Notably, ZEB1 rescue substantially reversed the inhibitory effects of wogonoside on GSC sphere formation and stemness marker expression, and restored the expression of ZEB1 target genes. Consistent with the in vitro findings, wogonoside markedly inhibited GSC-derived tumor growth and prolonged the survival of orthotopic glioma-bearing mice. CONCLUSION:This study reveals a novel antitumor mechanism of wogonoside in glioma, whereby it suppresses GSC stemness and malignant progression via PI3K/AKT inactivation and ZEB1-dependent transcriptional regulation. Wogonoside is a promising therapeutic candidate for the treatment of recurrent glioma.
INTRODUCTION:Cancer progression is characterized by metabolic reprogramming, including the enhanced Warburg effect, hypoxia-driven adaptations, ferroptosis regulation, and altered lipid metabolism. These metabolic changes promote tumor growth, survival, metastasis, and therapeutic resistance. This review aims to analyze the recent advances in nanoparticle-based strategies designed to target metabolic vulnerabilities in cancer and ameliorate therapeutic outcomes. METHODS:A comprehensive analysis of recent studies was performed to examine nanoparticle-based interventions targeting key metabolic pathways in cancer. Different nanocarrier platforms, including polymeric, lipidbased, metallic, and biomimetic nanoparticle was assessed regarding their design, targeting mechanisms, and metabolic dysregulation capabilities. RESULTS:Various nanoparticle systems have demonstrated considerable potential for selectively disrupting tumor metabolism. Polymeric nanoparticles provide controlled drug release and structural flexibility for targeted delivery. Conversely, lipid-based nanocarriers offer high biocompatibility. At the same time, metallic nanoparticles exhibit strong oxidative stress induction. Several studies also reported enhanced therapeutic efficacy through codelivery approaches and stimulus-responsive drug release. DISCUSSION:Targeting cancer metabolism through nanotechnology offers significant advantages over conventional therapies by improving drug stability, bioavailability, and tumor specificity. Nevertheless, major challenges remain, including metabolic adaptability, off-target toxicity, variability in nanoparticle accumulation, and manufacturing complexities. Addressing these barriers requires a deeper understanding of metabolic interactions within the tumor microenvironment and the development of more precise, safe, and scalable nanoparticles. CONCLUSION:Nanoparticle-mediated targeting of cancer metabolism represents a promising therapeutic strategy. However, successful clinical translation requires improved understanding of metabolic networks, optimized nanoparticle design, and standardized evaluation frameworks.
Gastrointestinal (GI) cancers-including colorectal, gastric, pancreatic, and esophageal malignancies- remain among the most prevalent and lethal cancers worldwide, largely due to their biological complexity and late-stage diagnosis. This narrative review examines the critical role of biomarkers in advancing personalized treatment strategies for GI cancers. Key diagnostic, prognostic, and predictive biomarkers, such as KRAS, HER2, PD-L1, microsatellite instability (MSI), and circulating tumor DNA (ctDNA), are discussed about their application in clinical decision-making. The review highlights biomarker-driven approaches across different GI cancer types, demonstrating how molecular profiling informs early detection, treatment selection, and monitoring of therapeutic response. Recent technological advances-including liquid biopsy, next-generation sequencing, and multi-omics integration- have expanded biomarker discovery and enhanced clinical utility. Challenges in implementing biomarker testing, such as variability in expression, lack of standardization, and limited accessibility, are also addressed. Overall, this article emphasizes the transformative potential of biomarkers to tailor therapy, improve patient outcomes, and shape the future of precision oncology in gastrointestinal cancers.
Introduction: Colorectal cancer (CRC) remains a significant global health burden; therefore, a better understanding of its molecular underpinnings is needed to develop more effective therapeutic methods. Traf2 and Nck-interacting kinase (TNIK) have emerged as key regulators in various malignancies, including CRC, but their exact roles and regulatory mechanisms remain only partially understood. The present study aimed to characterize TNIK expression in colorectal cancer through integrative analysis of two independent GEO microarray datasets (GSE9348 and GSE21510) comprising a total of 193 CRC and 37 normal tissue samples. Methods: Differential gene expression (DEG) analysis was conducted using GEO2R with the limma package, and protein-protein interaction network analysis was performed using STRING v12.0 and visualized in Cytoscape v3.8.2 to identify TNIK's functional partners within the Wnt signaling pathway. This work highlights genes that are up- and downregulated in CRC using a significance threshold of p < 0.05 and log FC > 1. Additionally, to investigate the epigenetic regulation of TNIK, an exploratory differential methylation analysis was performed on a murine CRC RRBS dataset (PRJNA589067) that models Wnt hyperactivation in APC-mutant CRC organoids. The data were processed through Bismark v0.24.2 for alignment and the Bioconductor package edgeR for DMR identification in the CpG context. Therefore, an epigenetic analysis of colorectal cancer was conducted to identify differentially methylated regions, using the thresholds p < 0.05 and logFC > 1. Results: DEG analysis reveals that TNIK is significantly upregulated in cancer samples. From DMR analysis, TNIK was observed to be relatively hypomethylated in the murine experimental model, while expression analysis of human CRC microarray data identified TNIK as an upregulated gene, an inverse relationship consistent with established epigenetic regulatory trends. Discussion: The data analyses and interpretations in this work provide a molecular basis for future pharmacological studies targeting TNIK kinase activity and aberrant DNA methylation in CRC, with potential implications for drug discovery efforts to restore normal Wnt pathway regulation. The study links changes in DNA methylation patterns to gene expression and provides important mechanistic definitions of how epigenetic modifications affect gene regulation. Conclusion: The overall contribution of TNIK overexpression to carcinogenesis and tumor progression through epigenetic modulation in CRC could be applied as a clinical biomarker or candidate for tumor suppressor genes in future studies.
INTRODUCTION:Gallbladder Cancer (GBC) remains one of the most aggressive biliary tract malignancies, frequently diagnosed at an advanced stage due to its subtle early symptoms. This review examines receptor-mediated drug delivery as a promising approach to address the challenges of late diagnosis, limited treatment options, and chemoresistance in GBC. METHODS:A structured literature review methodology was used to produce a comprehensive synthesis of evidence on available advances in receptor-targeted drug delivery and immunomodulatory strategies for Gallbladder Cancer (GBC). RESULTS:Emphasis is placed on exploiting specific cancer cell receptors, such as EGFR, HER2, VEGFR, FGFR, and the estrogen-related receptor, as targets for nanoparticles, liposomes, and antibody-drug conjugates to enhance drug internalization while reducing off-target toxicity. DISCUSSION:In parallel, the role of modern immunotherapies, including immune checkpoint inhibitors, cancer vaccines, and adoptive cell therapies such as CAR-T cells, is discussed with respect to their synergistic potential when combined with targeted drug-delivery systems. Additionally, emerging RNA- and gene-based therapies provide new avenues to modulate tumor biology and reverse treatment resistance. CONCLUSION:Collectively, integrating receptor-targeted nanomedicine with immunotherapeutic strategies could pave the way for personalized treatment regimens that improve therapeutic outcomes and survival in patients with gallbladder cancer.
Introduction: Breast cancer (BC) remains a primary driver of cancer-related mortality globally, necessitating the identification of novel molecular targets. While androgen receptor (AR) signaling is a recognized modulator of breast oncology, the therapeutic efficacy of selective androgen receptor modulators (SARMs), particularly S4 (Andarine), remains poorly characterized in this context. Methods: The anti-cancer activity of S4 was investigated across Estrogen Receptor-positive (MCF-7) and Triple- Negative (MDA-MB-231) models. Cellular viability, clonogenicity, and migratory capacity were assessed, alongside flow cytometric analysis of apoptosis and cell cycle distribution. Mechanistic insights were derived from quantitative gene expression profiling and untargeted LC-MS-based metabolomics. Results: S4 treatment induced a significant, dose-dependent reduction in cellular viability, suppressed clonogenicity and migration, and promoted apoptosis and cell cycle arrest, with MCF-7 cells exhibiting S-phase arrest and MDA-MB-231 cells exhibiting G0/G1-S arrest. Gene expression analysis revealed modulation of genes associated with apoptosis, stress response, and cell-cycle regulation, supporting the anti-cancer effects of S4. Metabolomic analysis further demonstrated that S4 exposure leads to marked remodeling of metabolic pathways associated with amino acid turnover, nucleotide homeostasis, lipid metabolism, and cofactor utilization. Discussion: These alterations point to a coordinated yet context-dependent metabolic response, characterized by shared core changes alongside distinct subtype-specific adaptations. Our findings suggest that S4 treatment is associated with significant alterations in breast cancer growth and metabolic pathways. Conclusion: The subtype-specific metabolic rewiring suggests that S4 exploits unique metabolic vulnerabilities, supporting further investigation of SARMs in breast cancer models.
Background: New medications and treatment approaches are needed due to the rising frequency of hepatocellular carcinoma; pharmacological combination therapy is one such approach that is being thoroughly studied. Methods: After co-treatment with atractylon and magnolol, cell viability and death were assessed using a CCK8 kit and an LDH kit, cell migration and invasion were assessed using a transwell assay, and related proteins were detected by western blotting after applying specific drug treatments or disturbances Results: In both HepG2 and Hep3B cells, magnolol and atractylon demonstrated significant synergistic effects, including the inhibition of cell proliferation, migration, and invasion. This mechanism may be mediated by the mTOR/TFEB signaling pathway. Discussion: Based on our experimental findings and the existing literature, the combined application of atractylon and magnolol is considered to have promising therapeutic potential for suppressing the growth of hepatocellular carcinoma cells. This warrants further investigation to elucidate the underlying mechanisms and optimize this combinatorial approach. Conclusion: The synergistic effect of magnolol and atractylon was found to be superior to that of either compound alone, particularly in terms of cell viability, migration, and invasion. The use of both drugs leads to autophagy-associated cell death, and the mTOR/TFEB signal pathway is an important factor in this process
Introduction: Innovative drug delivery systems are required to improve the therapeutic efficacy of cancer, which continues to be a global health challenge. Gelatin-based nanocarriers provide a prospective platform for targeted cancer therapy by utilizing their biocompatibility and stimuli-responsive properties, thereby addressing the limitations of conventional treatments. Methods: This review provides an overview of gelatin nanoparticles for the effective delivery of anticancer drugs. Various search databases were utilized for literature investigation, including PubMed, ScienceDirect, and Google Scholar. All the studies from the year 2015 to 2025 were added, along with patents associated with the field. Results: In lung, breast, melanoma, and other miscellaneous malignancies, gelatin nanoparticles exhibit reduced systemic toxicity and improved drug targeting. When combined with therapies, such as ultrasound or photothermal treatment, studies have demonstrated enhanced cellular absorption, sustained drug release, and synergistic effects. The increasing interest in their diagnostic and therapeutic applications is reflected in patents. Discussion: The improved treatment outcomes are facilitated by the versatility of gelatin nanocarriers, which allows for the tailored release of drugs in response to tumor-specific stimuli. Nevertheless, clinical implementation is impeded by obstacles, such as scalable production, nanoparticle stability, and unpredictable drug release. To surmount these obstacles, there are emerging strategies, such as stimuli-responsive and size-transformable nanoparticles. Conclusion: The precise delivery of drugs through gelatin-based nanosystems has the potential to revolutionise cancer therapy. To ensure their successful clinical application, it is essential to address current limitations through innovative engineering and integration with advanced therapeutic modalities.
INTRODUCTION:Chitosan Nanoparticles (CNPs), derived from the natural polymer chitosan, are increasingly recognized as highly versatile nanocarriers for delivering biological macromolecules in biomedical and biotechnological applications. Their utility in fields such as drug delivery, gene therapy, and tissue engineering is highly valued for their biocompatibility, biodegradability, and targeted delivery capabilities. However, comprehensive safety evaluations, including cytotoxicity and genotoxicity, are crucial before clinical or experimental applications. Green synthesis using plant extracts offers an eco-friendly route for nanoparticle production and may enhance biocompatibility. In this study, Martynia annua was employed, a plant with bioactive properties, to synthesize CNPs and evaluate their safety in vitro and in vivo. MATERIALS AND METHODS:CNPs were synthesized using an aqueous extract of Martynia annua via ionic gelation. Cytotoxicity was assessed in CHO-K1 cells using the chromosomal aberration assay across concentrations up to 2000 μg/mL. Genotoxic effects were evaluated in murine models using the micronucleus test at doses up to 2000 mg/kg. Standard controls were included to validate the assays. RESULTS:The CNPs demonstrated uniform morphology and nanoscale size. No significant cytotoxicity was observed in CHO-K1 cells, and chromosomal aberrations remained within baseline levels. Similarly, the in vivo micronucleus test showed no increase in micronuclei formation, indicating the absence of genotoxic effects even at high doses. DISCUSSION:These findings suggest that Martynia annua-derived CNPs are biocompatible and safe for cellular and systemic exposure. The green synthesis approach may further reduce the potential toxicity associated with chemical reagents. CONCLUSION:Naturally synthesized CNPs from Martynia annua are safe, non-cytotoxic, and non-genotoxic, supporting their potential application as nanocarriers for biological macromolecule delivery in therapeutic and biotechnological contexts.
Introduction: Colorectal cancer causes high global mortality. Natural compounds boldine and naringenin exhibit preventive potential by reducing oxidative stress, inhibiting cell proliferation, and regulating inflammation, making them promising, safer therapeutic agents. This study evaluated the chemopreventive potential of boldine and naringenin using DMH-induced Wistar rats, in silico EGFR binding studies, and in vitro antiproliferative assays. Methods: A multi-pronged approach was employed to evaluate the chemopreventive potential of boldine and naringenin. In silico molecular docking and dynamics simulations assessed binding affinity and stability with EGFR kinase, a key regulator of cancer progression. In vitro studies evaluated cytotoxicity in HCT116 colorectal cancer (CRC) cells using the MTT assay, and antioxidant activity was measured using the DPPH assay. In vivo, Wistar rats were divided into five groups: Control, DMH only, DMH + Boldine, DMH + Naringenin, and DMH + Vincristine. Lipid profiles, oxidative stress markers, and colon histopathology were analyzed. Results: Molecular docking revealed boldine’s stronger binding affinity (-8.75 kcal/mol) to EGFR kinase compared to naringenin (-7.43 kcal/mol), with dynamics simulations confirming stable interactions beyond 100 ns. In vitro, both compounds significantly reduced HCT116 cell proliferation dose-dependently and exhibited robust antioxidant activity in the DPPH assay. In vivo, boldine and naringenin counteracted DMH-induced lipid imbalances (by reducing serum cholesterol, LDL, VLDL, and TG levels, with a simultaneous increase in HDL) and modulated oxidative stress (by decreasing malondialdehyde and restoring glutathione, superoxide dismutase, and catalase levels; p<0.05). Histopathological analysis showed that both compounds, restoring nearnormal colon architecture, markedly alleviated DMH-induced hyperplastic polyps and crypt distortions. Discussion: Boldine and naringenin demonstrated chemopreventive potential by regulating lipid metabolism, bolstering antioxidant defenses, and preserving colon tissue integrity. Their strong EGFR interactions suggest utility as complementary therapies in CRC management, though further clinical validation is required to confirm their therapeutic potential. Conclusion: Boldine and naringenin effectively attenuated DMH-induced colorectal carcinogenesis by modulating lipid profiles, reducing oxidative stress, and mitigating histological abnormalities. Their multifaceted mechanisms highlight their promise as adjuvant therapies for CRC, necessitating further clinical studies.
Introduction: Glioblastoma (GBM), an aggressive and highly recurrent brain tumor, remains a significant challenge despite advancements in treatment. With a median survival of only 15 months and recurrence often occurring within a year despite aggressive initial therapy, there is an urgent need for more effective therapeutic strategies. The interplay of intrinsic and extrinsic factors, such as genetic mutations and alterations in the tumor microenvironment, drives recurrence, highlighting the importance of targeted approaches. Emerging therapies, particularly dendritic cell (DC)-based immunotherapies, show promise in enhancing anti-tumor immune responses. This study aimed to compare the effectiveness of DC-based immunotherapy in improving survival outcomes for patients with newly diagnosed or recurrent GBM. Methods: We conducted a comprehensive search across four electronic databases (Cochrane Central Register of Controlled Trials, PubMed, Scopus, and Web of Science) up to March 2024 to identify pertinent studies evaluating the efficacy of DC vaccines in the treatment of both newly diagnosed and recurrent GBM. The quality of evidence from trials was assessed using the Cochrane risk-of-bias version 1 (RoB1) tool. Data from the included studies were extracted into a standardized online sheet and analyzed using Review Manager (RevMan) 5.4. Results: Our search identified three records with a total of 355 patients. The results of the meta-analysis showed that DC-based immunotherapy had a greater impact on recurrent GBM than on newly diagnosed GBM. However, overall survival favored newly diagnosed cases, demonstrating a more protective effect (HR = 0.62, 95% confidence intervals (CI) (0.46,0.84), p = 0.002) with no significant heterogeneity (p = 0.97, I2 = 0%). A similar trend was observed for progression-free survival, favoring newly diagnosed cases over recurrent ones (HR = 0.56, 95% CI (0.31,1.00), p = 0.05), with no significant heterogeneity (p = 0.48, I2 = 0%). Moreover, comparable results were observed for survival at both 12 and 24 months Conclusion: Dendritic cell-based immunotherapy can enhance survival outcomes in GBM patients. The results showed DC-based immunotherapy to be more effective in newly diagnosed GBM than in recurrent cases.
Introduction: CDK4/6 kinases are crucial cell cycle regulators, and pharmacological inhibition of these kinases to block the G1-to-S phase transition has become an integral part of modern cancer therapy. Although five CDK4/6 inhibitors have been clinically approved, the development of acquired drug resistance greatly limits their long-term therapeutic efficacy. Methods: This review systematically summarizes the latest advances in CDK4/6 inhibitor research from 2022 to 2025, focusing on their structural features, biological functions, and preclinical research progress. In addition, this article comprehensively explores emerging therapeutic strategies, including bifunctional molecules and PROTAC-based protein degraders. Results: The action mechanisms of conventional CDK4/6 inhibitors have been relatively well elucidated. Notably, these emerging strategies have yielded encouraging preclinical results, including co-targeting CDK4/6 with other critical therapeutic nodes (e.g., HDAC, PARP1) and adopting PROTAC-based degraders to directly induce the degradation of target proteins. A growing number of innovative approaches targeting drug resistance via multi-target inhibition and induced protein degradation have been developed. Distinct from classical singletarget monotherapy, these innovative strategies leverage distinct pharmacological pathways, offering feasible research directions to improve therapeutic efficacy and delay drug resistance. Discussion: In-depth understanding of CDK4/6 inhibitors and the continuous development of bifunctional agents and protein degraders provides key theoretical and technical support for the design of next-generation therapeutic strategies to address current clinical limitations. These research advances are expected to facilitate the development of more effective and long-lasting therapeutic modalities for tumor treatment. Conclusion: This review summarizes recent advances in CDK4/6 inhibitors. Novel dual-target and PROTACbased strategies offer promising resistance-overcoming tumor therapies.
One of the leading causes of death related to cancer worldwide is non-small cell lung cancer (NSCLC). Epidermal growth factor receptor (EGFR) mutations are one of the most important therapeutic targets. Lazertinib is an irreversible EGFR tyrosine kinase inhibitor (TKI) that is selectively active against EGFR mutations and the T790M resistance mutation, but not against wild-type EGFR. In this paper, we have evaluated the significant role of lazertinib in the treatment of NSCLC, compared with agents, such as osimertinib. We have analyzed the pharmacological benefits, clinical trial evidence, and interactions with the central nervous system (CNS), as well as its active role in first-line therapy beyond acquired resistance. The early-phase results are promising, but queries regarding resistance mechanisms and treatment protocols remain. We have conducted a detailed investigation of lazertinib's therapeutic properties, its role in combination therapies, and its potential to improve treatment outcomes in EGFR-mutant NSCLC. We aimed to highlight both the opportunities and clinical uncertainties associated with lazertinib in cancer care.
Telisotuzumab Vedotin (Teliso-V), previously known as ABBV-399, is a novel, first-in-class antibodydrug conjugate developed by AbbVie. It combines an anti-c-Met monoclonal antibody (ABT-700) with monomethyl auristatin E (MMAE), a potent microtubule-disrupting agent, via a cleavable linker. This design allows selective delivery of the cytotoxic payload to c-Met-overexpressing tumour cells, thereby bypassing reliance on MET signalling for efficacy. Preclinical studies demonstrated that ABBV-399 effectively inhibited the growth of xenograft tumors refractory to other MET-targeted inhibitors. In early Phase I trials, the agent showed a favourable safety profile and elicited objective tumour responses in c-Met-expressing non-small cell lung cancer (NSCLC) patients. In the Phase II LUMINOSITY study, which served as the basis for accelerated FDA approval, Teliso-V demonstrated an overall response rate (ORR) of 35% and a median duration of response (DOR) of 9 months in patients with high c-Met protein overexpression. Continued approval may depend on confirmatory Phase III data.
Introduction: Cancer cells exhibit metabolic characteristics known as the Warburg effect, which is aerobic glycolysis. Tan IIA, a compound from Salvia miltiorrhiza, has antitumor effects, but its impact on prostate cancer metabolism is not fully understood. Methods: The effects of Tan IIA on prostate cancer cell proliferation and apoptosis were assessed. Glucose metabolism was evaluated by measuring glycolysis-related metabolic changes and the expression levels of key metabolic enzymes. The underlying molecular mechanisms were investigated by analyzing the AKT/mTOR/ HIF-1α signaling pathway and the role of CD147. Results: Tan IIA significantly suppressed prostate cancer cell proliferation and induced apoptosis by inhibiting glucose metabolism. Treatment with Tan IIA downregulated hypoxia-inducible factor-1α (HIF-1α) expression via blockade of the AKT/mTOR signaling cascade. This resulted in reduced expression levels of critical glycolytic regulators, including glucose transporter 1 (GLUT1), pyruvate kinase M2 (PKM2), and hexokinase 2 (HK2). Furthermore, CD147 silencing impaired glycolysis, an effect potentiated by Tan IIA, suggesting a mechanism involving CD147 inhibition. Discussion: Tan IIA disrupts the glycolytic pathway in prostate cancer cells by suppressing the activity of the AKT/mTOR/HIF-1α axis and potentially through CD147 modulation Conclusion: In summary, these results establish Tan IIA as a potential antitumor compound worthy of further preclinical investigation that exerts its antitumor activity by targeting the unique metabolic dependencies of prostate cancer.
INTRODUCTION:The evolution of resistance to different types of cancer therapies has become a significant challenge in oncology research, leading to disease progression and limited treatment options. Rechallenge therapy, where a previously used treatment is reintroduced after a period of discontinuation, has emerged as a potential strategy to overcome resistance. METHODS:This review synthesizes current knowledge on rechallenge therapy by analyzing data from clinical trials, retrospective studies, and case reports. A comprehensive examination was conducted across multiple cancer types and therapeutic classes, including immunotherapy, chemotherapy, targeted therapy, hormonal therapy, and combination approaches. RESULTS:The efficacy of rechallenge therapy varies across cancer types. For instance, in metastatic colorectal cancer, anti-EGFR rechallenge therapy has shown response rates of 20-30% in RAS wild-type patients after a drug-free interval. In prostate cancer, rechallenge with androgen deprivation therapy or abiraterone has demonstrated biochemical response rates of approximately 30-40% in selected populations. DISCUSSION:In hormone receptor-positive breast cancer, endocrine therapy rechallenges, especially following a treatment break, have yielded clinical benefit rates of over 40% in some cohorts. These outcomes are influenced by tumor biology, duration of prior response, molecular profiling, and patient selection criteria. CONCLUSION:Rechallenge approaches show promise as viable options for treating cancer recurrence and resistance, but their application must be carefully tailored to each patient. A well-planned scientific strategy is required to optimize different rechallenge approaches, identify predictive biomarkers, and understand the longterm outcomes associated with this method.
Chimeric antigen receptor (CAR)-T cells are synthetic receptors used for the recognition of specific antigens expressed by reprogrammed T cells for targeting tumors. CAR-T cell therapy has gained remarkable clinical success for the treatment of hematological malignancies such as chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL), diffuse large B-cell lymphoma (DLBCL), lymphoplasmacytic lymphoma (LPL), and primary intraocular lymphoma (PIL). The increasing number of preclinical investigations and clinical trials is focusing on extending CAR-T cell therapy to solid tumors due to its remarkable success in leukemia and lymphoma cancers. However, some limitations of CAR-T therapy still exist, including a lack of targetable antigen diversity, heterogeneous antigen expression, insufficient T-cell trafficking efficiency, and an immunosuppressive tumor microenvironment. This review explores the role of CAR-T cell therapy, current challenges, and emerging solutions for solid tumor malignancies. To overcome the existing limitations of CAR-T cell therapy, innovative strategies, including the optimization of novel CAR vectors with checkpoint inhibitors, have been designed to enhance the antitumor activity of CAR-T cells against solid tumors. It also explores the design of novel CAR-T cells and strategies for improving antitumor activity against solid tumors. Among the emerging strategies, universal CARs and combination approaches with checkpoint inhibitors are especially promising for extending CAR-T therapy to solid tumors.
