Chemotherapy and immune checkpoint inhibitors (ICIs) are widely utilized in cancer treatment, exerting not only direct cytotoxic effects on tumor cells but also significantly reshaping the systemic immune status of patients, particularly the composition and function of the T cell repertoire. This review begins with the analysis of the widespread depletion and dysfunction of early T cell subsets in cancer patients, particularly naïve T cells (Tn) and stem-like memory T cells (Tscm). Afterward, it details how chemotherapy and ICIs differentially regulate T cell homeostasis, including their ability to induce T cell exhaustion and differentiation skewing, as well as their ability to stimulate immunity and remodel the tumor microenvironment. On this basis, it is shown that the quality of T cell memory phenotypes is central in determining the in vivo expansion and persistence of chimeric antigen receptor T (CAR-T) cells. To overcome the challenges of classical autologous CAR-T therapy, which stems from raw material quality and in vitro manufacturing bottlenecks, we focus on transforming chemotherapy and ICIs from traditional treatment modalities into beneficial "host preconditioning" regimens aimed at optimizing the baseline state of the endogenous T cell repertoire. All in all, this transformation of traditional therapies into host preconditioning strategies, along with recent advances in in vivo CAR-T approaches, provides theoretical grounds and translatable clues to develop next-generation cellular immunotherapy.
Calcium electrochemotherapy (CaECT) is an effective alternative to standard chemotherapeutic treatments, utilizing intracellular delivery of supraphysiological calcium concentrations to induce cell death. High-frequency sub-microsecond bursts can be successfully used for CaECT, however, bipolar waveforms have not yet been characterized in this context, potentially offering better impedance mitigation and more uniform treatment when compared to unipolar procedures. Therefore, this study evaluated the feasibility of unipolar and symmetric bipolar sub-microsecond pulses (7 kV/cm × 300 ns × 250, 1 MHz) for CaECT including their capacity to modulate antitumor immunity in a moderately immunogenic murine breast cancer model. Standard microsecond protocol (1.5 kV/cm × 100 μs × 8 pulses at 1 Hz) was used as a reference. In vitro data revealed that a bipolar cancellation phenomenon when symmetric bipolar pulses were applied, whereas this effect was not detected in vivo. CaECT treatment induced systemic immune alterations across electroporation groups, including increased CD4+ and CD8+ memory T-cell populations in the spleen and reduced CD4+ regulatory T cells and myeloid-derived suppressor cells in tumor-draining lymph nodes. Unipolar nanosecond pulses showed a clearer increase in central memory T-cell populations, while bipolar pulses were associated with pronounced modulation of lymph-node immune composition. It is shown that bipolar cancellation phenomenon is not necessarily triggered in vivo, which was predicted by in vitro data.
Diffuse large B cell lymphoma (DLBCL) presents a critical clinical challenge due to declining chemosensitivity and difficult-to-manage dose-limiting toxicities. Although gut microbiota modulation shows potential for "toxicity reduction and efficacy enhancement", its mechanism in DLBCL remains unclear. Comparative analysis revealed a marked reduction of beneficial bacteria in patients with DLBCL versus healthy volunteers, with a marked decrease in the abundance of core probiotics, particularly Limosilactobacillus reuteri. Fecal microbiota transplantation from healthy donors into DLBCL mouse models reduced tumor burden, improved chemosensitivity, and alleviated intestinal toxicity. A core probiotic strain, L. reuteri HG001, was isolated and shown to replicate these effects alone, with the tryptophan metabolite indole-3-carbaldehyde (ICAld) identified as the key component responsible for its adjunctive antitumor activity. Mechanistic studies demonstrated that ICAld exerts significant adjunctive antitumor effects both in vitro and in vivo in a dose-dependent manner in mouse models; it acts by activating the aryl hydrocarbon receptor (AHR)/cytochrome P450 family 1 subfamily A member 1 (CYP1A1)/reactive oxygen species (ROS) axis, inhibiting the phosphatidylinositol 3-kinase (PI3K)/AKT/mechanistic target of rapamycin (mTOR) signaling pathway, promoting apoptosis, and synergizing with cyclophosphamide. An aryl hydrocarbon receptor antagonist reversed both the chemosensitizing and intestinal protective effects of L. reuteri HG001 and ICAld. This study elucidates a microbiota-mediated mechanism in DLBCL and supports L. reuteri HG001 as a probiotic adjuvant to enhance therapy while reducing toxicity.
The aim of this study was to assess the inflammatory status of patients with pancreatic cancer (PC) prior to the initiation of the first course of chemotherapy and to ascertain the most precise systemic inflammation index for predicting overall survival (OS). A single-centre retrospective analysis involving 310 pa- tients with PC was conducted. Blood samples were collected from patients during chemotherapy qualification, either on the first day of chemotherapy or the day before the first chemotherapy dose. The following inflammatory indices were calculated: systemic immune-inflammation index, systemic inflammation response index, and inflammatory benchmark index (IBI). Statistical analyses were performed utilizing appropriate tests (e.g., the log-rank test). All parameters were significant predictors of mortality; however, their area under the curve indicated only a moderate ability to differentiate mortality risk. Among the indices analysed, IBI was the sole metric that predicted OS in adjuvant (p < 0.05) and palliative (p < 0.001) cohorts, alongside disease-free survival (p < 0.04) and progression-free survival (p < 0.009). In the multivariate analysis, only IBI was proven to be statistically associated with OS (p < 0.043). Furthermore, IBI well stratified the tumour stage. All analysed indices related to inflammation and immune response may function as prognostic markers; however, additional studies are required to determine their precise cut-off value. In our investigation, IBI exhibited a distinctive protective effect, culminating in a 65% reduction in mortality, thereby underscoring the importance of C-reactive protein in patient stratification.
Paclitaxel, a natural diterpenoid compound derived from Taxus species, is one of the most successful plant-based anticancer drugs and has been widely applied in the treatment of various solid tumors. In recent years, emerging evidence has suggested its potential efficacy in refractory or advanced colorectal cancer (CRC), particularly in patients resistant to standard first-line chemotherapy such as 5-fluorouracil (5-FU). However, responses to paclitaxel in CRC are heterogeneous. This study aimed to elucidate the metabolic determinants underlying the heterogeneous response of CRC to paclitaxel and to identify serum metabolites associated with therapeutic response. Integrated serum metabolomic profiling was performed in patient-derived tumor organoid (PDTOs, n=18), combined with drug sensitivity assays and in vivo validation using mouse xenograft models. An analysis was conducted to sensitivity of paclitaxel, followed by targeted metabolomic quantification and pathway enrichment to identify key metabolites influencing paclitaxel efficacy. Linoleic acid (LA) was identified as a serum metabolite significantly correlated with reduced paclitaxel sensitivity. Elevated LA levels attenuated paclitaxel-induced G2/M cell cycle arrest and reduced cytotoxicity by altering microtubule dynamics. Functional validation in CRC cell lines and animal models further confirmed that LA diminished the antitumor effect of paclitaxel, supporting a metabolism-mediated mechanism of chemoresistance. This study identifies serum linoleic acid as a metabolism-related candidate biomarker associated with paclitaxel resistance in CRC. These findings highlight the potential clinical relevance of metabolic factors in modulating chemotherapy response and suggest that LA may have potential relevance for patient stratification in future studies of paclitaxel response in CRC.
Chylous ascites is an uncommon condition characterized by the accumulation of triglyceride-rich, milky fluid in the peritoneal cavity due to lymphatic disruption or obstruction. Although lymphoma is a leading cause of malignant chylous ascites, its occurrence as an initial presentation remains rare. A 69-year-old woman presented with a three-month history of postprandial abdominal pain, weight loss, anorexia, and dyspnea. Imaging revealed extensive abdominal and pelvic lymphadenopathy with bilateral pleural effusions. Diagnostic laparoscopy demonstrated milky peritoneal fluid, and fluid analysis confirmed chylous ascites (triglycerides, 1361 mg/dL). Lymph node biopsy demonstrated high-grade B-cell lymphoma with morphological features favoring follicular lymphoma. Immunohistochemistry revealed a markedly elevated Ki-67 proliferative index (> 90%), and genomic profiling identified pathogenic EZH2 and TET2 mutations with a high tumor mutational burden. According to the fifth edition of the WHO Classification of Haematolymphoid Tumours (2022), these findings are most consistent with follicular lymphoma, a mature B-cell neoplasm with high-grade features. Given the high-output drainage and recent surgery, cytotoxic chemotherapy was deferred, and rituximab monotherapy was initiated. Rapid clinical improvement and decreased drain output allowed safe transition to standard R-CHOP therapy, achieving a complete metabolic response (Deauville score 2) after six cycles. This case highlights chylous ascites as a rare but important presenting feature of lymphoma. Its recognition should prompt early histopathologic evaluation and multidisciplinary management. In selected postoperative or frail patients, rituximab monotherapy can serve as an effective bridge to full chemotherapy, facilitating recovery and improving outcomes. Early diagnosis and targeted treatment remain essential to prevent complications from lymphatic loss and to optimize prognosis in lymphoma-associated chylous ascites.
Chemotherapy drugs are known to cause peripheral neuropathy of varying severity. However, Bell's palsy, which is an acute lower motor neuron facial nerve palsy, is rarely observed in oncology patients receiving chemotherapy. We report a case of Bell's palsy in a 74-year-old male metastatic lung adenocarcinoma patient while on treatment with nab-paclitaxel and pregabalin. Temporal association, diagnostic workup, and management are discussed in this case report to highlight the importance of differentiating neurological adverse effects in cancer therapy. The most likely causative factor remained nab-paclitaxel-induced Bell's palsy in our patient. However, viral reactivation due to immunosuppression resulting from drug toxicity cannot be completely ruled out.
Oropharyngeal carcinoma (OPC) represents one of the most rapidly increasing head and neck cancers worldwide, with prognosis strongly influenced by human papillomavirus (HPV) infection. Given the clinical significance, there is a strong demand to evaluate novel biomarkers to monitor treatment outcomes. Therefore, we conducted a study to assess the prognostic value of citrulline, a well- established marker of enterocyte injury, in patients undergoing OPC treatment. We reanalysed a cohort of patients with OPC recruited across three tertiary oncology centres in Poland. All patients were treated with intensity-modulated radiotherapy, with concurrent chemotherapy. Serum citrulline levels were measured prior to treatment using a dedicated ELISA kit. The associations between pre-treatment citrulline levels, clinical characteristics, and patient survival outcomes were evaluated. A total of 64 patients treated with chemoradiotherapy (CRT) were included. The baseline citrulline level showed no significant association with clinical characteristics. In univariable Cox regression, tumour size, along with induction chemotherapy, were significantly associated with poorer overall survival (OS) and progression- free survival (PFS). In contrast, the baseline citrulline level was not predictive in univariate analysis. In the subgroup analysis of patients with positive HPV status, both the larger tumour size and higher citrulline level were significantly associated with poorer OS and PFS. Baseline citrulline demonstrated prognostic value for OS and PFS in HPV-positive patients treated with CRT. These findings suggest a potential role for citrulline as a biomarker of treatment-related vulnerability in OPC and warrant further validation in larger, independent cohorts.
Traditional metal-organic frameworks (MOFs) suffer from limited responsiveness to the complex tumor microenvironment, systemic toxicity from non-specific distribution, and compromised Fenton-like efficiency due to antioxidants. To address these, we propose a multi-modal synergistic strategy to functionalize MOFs and achieve chemodynamic and photothermal synergy without chemotherapeutics. A replacement MOFs system (FHMGA) integrated with hyaluronic acid, glucose oxidase, and gold nanoparticles is designed based on CD44 receptor recognition. In the acidic TME, FHMGA degrades and is reduced by overexpressed glutathione to Fe2+ and Mn2+ for further reaction with endogenous H2O2 via Fenton-like reactions to generate ·OH and induce oxidative stress. Under near-infrared irradiation, gold nanoparticles exhibit high photothermal conversion efficiency, triggering local hyperthermia for thermal ablation. Simultaneously, heat enhances glucose oxidase-powered catalysis, which catalyzes glucose oxidation in cancer cells to disrupt energy metabolism and produce additional H2O2, further boosting Fenton-like reactions. Our results demonstrate that FHMGA exhibits significant anti-tumor efficacy with minimal systemic toxicity. The triple synergy of oxidative damage from chemodynamic therapy, thermal ablation from photothermal therapy, and metabolic disruption via glucose oxidase significantly inhibits cancer cell growth by overcoming antioxidant-mediated limitations. Self-amplifying Fenton catalysis, while responsive degradation reduces systemic toxicity. This work advances precise cancer therapy by establishing a chemotherapy-free, multi-responsive synergistic system, addressing critical bottlenecks of ferrium-based MOFs and providing a safer, more effective strategy for tumor-specific treatment.
Two-dimensional porphyrin-based metal-organic frameworks (2D Por-MOFs) have emerged as promising candidates in biomedical applications due to their ultrathin morphology, high surface area, tunable electronic properties, and excellent optical characteristics. This review systematically summarizes recent advances in their utilization for cancer therapy, antibacterial treatment, and biosensing. In oncology, 2D Por-MOFs serve as efficient photosensitizers for photodynamic therapy (PDT) by generating reactive oxygen species (ROS) to eradicate tumor cells, while also enabling synergistic therapeutic outcomes through integration with chemodynamic therapy (CDT), chemotherapy, immunotherapy, sonodynamic therapy (SDT), and novel mechanisms such as copper-dependent cell death. For antibacterial applications, these materials enhance ROS production via size engineering, single-atom modification, or nanozyme loading, effectively killing pathogens and promoting wound healing, as well as being incorporated into smart dressings to achieve combined hemostatic and antimicrobial functions. In biosensing, 2D Por-MOFs act as ideal platforms for photoelectrochemical signal transduction or fluorescent probes, facilitating the development of highly sensitive fiber-optic SPR, electrochemical, and fluorescence sensors capable of detecting disease biomarkers, pathogens, small-molecule metabolites, and ions with high sensitivity. Finally, the current challenges and future prospects for the clinical translation of 2D Por-MOFs are discussed.
Polysaccharides comprise a structurally varied class of natural macromolecules found in plants, fungi, animals, marine algae, and microorganisms. Therefore, they have attracted considerable attention over several decades due to numerous anticancer-associated activities indicated by accumulating in vitro and in vivo evidence, along with clinical data of heterogeneous maturity-ranging from well-established adjuvants such as lentinan and PSK, which have demonstrated survival benefits in randomized controlled trials, to early-phase exploratory studies for agents like fucoidan. Traditional chemotherapeutic agents (e.g., alkylating agents, antimetabolites) exert direct cytotoxic effects; however, many contemporary small-molecule drugs-such as kinase inhibitors and hormone receptor modulators-act through targeted inhibition of oncogenic signaling, and immunotherapies (e.g., checkpoint inhibitors) function by enhancing endogenous anti tumor immunity rather than directly damaging tumor cells, as cytotoxic agents do. By contrast, polysaccharides are increasingly recognized as biological response modifiers that exert an impact on cancer development through, for instance, immune system functioning, redox, and/or inflammatory balance, communications between cancer and stromal cells of the tumor microenvironment, and intracellular signaling cascades. This review presents an outline of the structural variability, physiological sources, and functions of polysaccharides relevant to cancer treatment. Based on the present armamentarium of polysaccharides, the main modes of action are summarized in terms of immunomodulation through the engagement of pattern-recognition receptors, oxidative stress and inflammation regulation, quantifiable programmed cell death modes, angiogenesis and metastasis, and indirect regulation of oncogenic signaling pathways. These are first expressed in terms of the target-unrelated context and at the network level. Finally, we briefly discuss recent developments regarding polysaccharides as coadjuvants in chemotherapy, radiotherapy, and immunotherapy, in addition to their status as potential biomaterials in novel drug delivery systems. Critical reviews of relevant issues regarding structural heterogeneity and reproducibility, pharmacokinetics, and clinical translation are given. Indeed, this review presents polysaccharides as multi-functional components in multi-dimensional cancer therapy, paying due attention to appropriate structural elucidation, mechanism validation, and systems-oriented approaches to their rational development and clinical application.
2-oxoglutarate-and iron-dependent oxygenase domain-containing protein 1(OGFOD1) is a prolyl hydroxylase that plays a pivotal role in regulating protein synthesis accuracy and efficiency. OGFOD1 is implicated in the pathogenesis of various cancers, including lung cancer, breast cancer and colonic cancer. A recent study highlights that under chemotherapy pressure, the upregulation of OGFOD1 promotes global protein synthesis via its catalytic activity, which is a key mechanism for AML chemoresistance. Deleting of OGFOD1 specifically compromises AML translation adaptability, thereby eradicating post-chemotherapy resistant cells and extending survival in vivo, while sparing normal hematopoiesis. Consequently, targeting OGFOD1 with identified inhibitors presents a promising therapeutic strategy to disrupt the translational adaptability of AML cells, potentially overcoming chemoresistance and improving patient outcomes. More importantly, there is an urgent need to develop highly selective OGFOD1-targeted agents with minimal toxicity.
Lung cancer remains a leading cause of global cancer-related mortality, with most patients diagnosed at advanced stages. The emergence of immune checkpoint inhibitors (ICIs), specifically targeting PD-1/PD-L1 and CTLA-4 pathways, has revolutionized the treatment landscape by restoring anti-tumor immune responses. Currently, ICIs are integrated into clinical practice across all stages of lung cancer, administered either as monotherapy or in combination with chemotherapy, radiotherapy, and anti-angiogenic agents. Despite significant survival benefits, several critical challenges persist. First, primary and acquired resistance, driven by tumor microenvironment (TME) immunosuppression, impaired antigen presentation, and aberrant signaling, limits long-term efficacy. Second, existing biomarkers like PD-L1 expression and tumor mutational burden (TMB) face limitations due to insufficient standardization and spatiotemporal heterogeneity. Furthermore, immune-related adverse events (irAEs) across multiple organ systems necessitate vigilant clinical management and occasionally treatment discontinuation. This review systematically evaluates the research progress and clinical applications of ICI therapy in lung cancer. We highlight the therapeutic heterogeneity observed across different histological types, including non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), with a specific focus on the management of brain metastases (BMs). Additionally, the article discusses varying response patterns within specific patient subgroups, such as geriatric patients and individuals with differing smoking or performance statuses. By synthesizing data on both favorable therapeutic outcomes and the spectrum of irAEs, we emphasize the necessity of personalized immunotherapy. Ultimately, this review looks forward to future advancements aimed at enhancing the precision and safety of lung cancer treatment, providing a roadmap for more tailored clinical interventions.
A 56-year-old man presented with weight loss, abdominal pain, and altered bowel habits. Computed tomography revealed an appendiceal mass with hepatic lesions and regional lymphadenopathy, suggestive of advanced appendiceal malignancy. Surgical exploration identified a mucin-producing appendiceal tumor with metastatic involvement of the mesentery, liver, and lymph nodes. Histopathological examination confirmed an invasive, moderately differentiated mucinous adenocarcinoma of the appendix, without lymphovascular or perineural invasion. The mesenteric lesion showed malignant neoplastic cells consistent with metastatic appendiceal adenocarcinoma, infiltrating the surrounding tissue. The patient underwent surgical resection followed by systemic chemotherapy. During follow-up, clinical evolution was consistent with advanced metastatic disease requiring ongoing multidisciplinary management. This case highlights the diagnostic and therapeutic challenges of advanced appendiceal mucinous adenocarcinoma and emphasizes the importance of complete pathological characterization and coordinated oncologic care.
Metronomic cyclophosphamide is occasionally used as maintenance therapy for patients with metastatic triple-negative breast cancer (TNBC), although there is limited long-term safety data. In this case study, we present the patient with metastatic TNBC who achieved a durable complete response and subsequently received metronomic cyclophosphamide for seven years. Progressive cytopenias prompted an investigation, which revealed myelodysplastic syndrome with monosomy 7 once reversible causes had been addressed, including vitamin deficiencies, Helicobacter pylori infection and previous hepatitis C exposure. Following discontinuation of cyclophosphamide, gradual haematological recovery was observed, and the patient remains without radiological evidence of progression. This case highlights the potential for late haematological toxicity associated with prolonged exposure to low doses of alkylating agents, emphasises the need for periodic reassessment of maintenance therapy in long-term responders, and shows that persistent cytopenias require evaluation of alternative causes rather than being solely attributed to chemotherapy.
Uterine mesonephric-like adenocarcinoma (MLA) is a rare and biologically aggressive subtype of endometrial carcinoma, estrogen receptor (ER) and progesterone receptor (PR) are typically absent or exhibit very low expression in this type of cancer. The cornerstone of treatment is still surgical resection, frequently in combination with chemotherapy or radiation therapy. There is currently disagreement over the optimal therapeutic regimen. A 60-year-old postmenopausal woman presented with vaginal bleeding as the initial symptom. Computed tomography (CT) imaging revealed a uterine mass, and postoperative histopathology confirmed a diagnosis of mesonephric-like adenocarcinoma of the uterus. This case demonstrates dual ER/PR positivity, representing the first reported instance of this rare clinical subtype. This study aims to enhance clinicians' recognition and management of uterine mesonephric-like adenocarcinoma. MLA with hormone receptor expression may exhibit distinct biological behavior. Future studies with larger cohorts and longer follow-up are needed to explore whether these tumors could represent a candidate for endocrine-based therapeutic approaches.
Radiotherapy (RT) remains a cornerstone of cancer management but is fundamentally constrained by normal tissue toxicity, intrinsic and acquired radioresistance, and hypoxia- and microenvironment-driven dose-response plateaus. Engineered nanomaterials offer a versatile toolbox to reshape this therapeutic landscape by coupling enhanced energy deposition with microenvironmental and biological reprogramming. This review summarizes recent advances in nanomaterial-enabled radiosensitization from four interlocking dimensions: (i) high-atomic-number platforms that amplify local dose via photoelectric and related interactions and thereby increase microscopic energy deposition; (ii) chemical radiosensitization through modulation of reactive oxygen species (ROS), including Fenton/Fenton-like catalysis and depletion of glutathione (GSH)/thioredoxin antioxidant networks; (iii) tumor microenvironment (TME) remodeling strategies that alleviate hypoxia, buffer acidity, rewire redox and metabolic states, relieve immune suppression, and normalize vasculature and extracellular matrix (ECM) to broaden the effective therapeutic window; and (iv) biological radiosensitization targeting DNA damage response (DDR), cell-cycle redistribution, and multiple programmed cell-death pathways such as apoptosis and ferroptosis. We further discuss nano-delivery architectures-passive EPR-based systems, ligand-directed and biomimetic carriers, and stimuli-responsive (pH, hypoxia, redox, or irradiation triggered) formulations-that co-load radiosensitizers, chemotherapeutics, and molecularly targeted agents, as well as theranostic platforms integrating computed tomography (CT)/magnetic resonance imaging (MRI)/optical contrast for image-guided, dose-adapted treatment. Emerging multimodal regimens, including radiotherapy combined with photothermal, sonodynamic, chemotherapy, and immunotherapy on a single nano-platform, are highlighted for their capacity to achieve genuine "1 + 1>2" synergy. Finally, we outline key translational challenges-industrial-scale, standardized manufacturing; long-term safety and clearance; inter-patient and spatiotemporal heterogeneity; quantitative linkage between imaging signals, dose, and biological effect; and the integration of biomarkers and artificial intelligence into personalized nano-radiotherapy-and propose future directions to accelerate clinical implementation.
Breast cancer is a significant health problem worldwide, being the most frequent cancer in females and one of the most lethal. The current approach to breast cancer has moved away from the morbid Halsted radical mastectomy to breast-conserving surgery (BCS). Although BCS, supplemented by radiotherapy, has the same survival rates as the Halsted procedure, it is associated with significantly good post-operative outcomes. Oncoplastic breast surgery (OBS) combines the principles of breast cancer removal and reconstruction, allowing for the removal of larger tumors while maintaining the breast appearance by reshaping the breast tissue. In this article, the current evidence for the clinical, cosmetic, and oncological outcomes of OBS is reviewed. The evidence demonstrates the safety and potential benefits of OBS in comparison to BCS in the removal of breast cancer. The article provides a background on the various classifications of OBS, including the evolution from volume-based to ptosis-based classifications by the American Society of Breast Surgeons. A comparison is made between volume displacement techniques, such as therapeutic mammoplasties, and volume replacement techniques, including regional perforator flaps and fat grafts. The article also discusses the challenges facing the adoption of OBS across the world, including the disparity in training between surgeons in developed and developing countries. Additionally, the article presents the challenges facing the adoption of OBS, including the risk of fat necrosis and fibrosis. The article also presents the future direction in the development of OBS, including the use of extreme oncoplastic techniques in the removal of breast cancer using neoadjuvant chemotherapy. Additionally, the article presents the use of artificial intelligence in the pre-operative modeling of breast tissue using robotic-assisted tissue transfer. OBS is the current gold standard in the removal of breast cancer.
This review examines the evolving first-line immunotherapy landscape in metastatic renal cell carcinoma (mRCC), with emphasis on the comparative clinical logic of dual immune checkpoint blockade (ICI-ICI) and immune checkpoint inhibitor-tyrosine kinase inhibitor combinations (ICI-TKI), the persistent efficacy-effectiveness gap, biomarker development, and translational resistance biology. Pivotal phase III trials have established superior survival for contemporary ICI-based regimens over sunitinib; however, cross-trial heterogeneity, differences in IMDC risk distribution, varying toxicity profiles, and selection of fitter trial populations complicate simple regimen ranking. Real-world studies confirm that outcomes in routine practice are frequently less favorable than those reported in registration studies, but these differences are partly explained by confounding related to performance status, comorbidity burden, access to care, toxicity management, and treatment sequencing. Renal cell carcinoma remains a biomarker-challenged disease in which PD-L1 and tumor mutational burden have limited predictive value, while PBRM1 status, VHL-driven pseudohypoxia, and spatial immune architecture are biologically informative but not yet clinically validated as stand-alone selection tools. Resistance arises through tumor-intrinsic metabolic reprogramming, impaired antigen presentation, compensatory checkpoint signaling, and stromal-myeloid exclusion within the tumor microenvironment. Taken together, the field is moving from empirical regimen selection toward a model that integrates disease tempo, patient fitness, translational biomarkers, and mechanism-based sequencing. Future progress will depend on composite biomarker validation, biomarker-enriched trials, rational resistance-directed combinations, and structural measures that improve external validity and equitable access.
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a chronic liver disease with rising prevalence and disease burden. However, despite recent therapeutic advances, effective and broadly applicable treatment options remain limited, prompting continued efforts to develop novel therapeutic agents. Traditional Chinese Medicine (TCM) has attracted growing interest in MASLD management because its bioactive compounds can target multiple pathogenic processes. However, many TCM-derived compounds are limited by poor solubility, low bioavailability, and insufficient tissue specificity. Nanotechnology-based formulations enable controlled release and targeted delivery, offering a strategy to improve the utilization and therapeutic efficacy of TCM-derived active ingredients against MASLD. Based on a structured literature search across four databases, 45 representative studies were included and narratively synthesized according to nanoplatform type, design features, and mechanism-related therapeutic actions. Compared with previous broader reviews on TCM nanomedicine or MASLD-related nanotherapies, this review particularly emphasizes MASLD-oriented TCM nanoformulations from the perspectives of platform classification, design features, and mechanism-related therapeutic actions. We also discuss current challenges and future directions for clinical translation.