A significant proportion of patients fail to respond adequately to the standard R-CHOP regimen for diffuse large B-cell lymphoma (DLBCL). Rapid proliferation requires energy and the interaction between H+ ions and mitochondria suggests that regulating acid secretion in tumor cells may be a therapeutic strategy for DLBCL. This study constructed a macrophage membrane-coated liposomal formulation (MM-Lipid@Vpz) for the targeted delivery of vonoprazan to combat DLBCL, which enables the evasion of the reticuloendothelial system, ensuring enhanced specificity in tumor targeting.

Chemodynamic therapy (CDT) is a promising antitumor strategy that damages tumor cells by generating reactive oxygen species (ROS) to induce oxidative stress. However, antioxidant mechanisms in tumor cells greatly reduce CDT efficacy.

The integration of artificial intelligence (AI) into oncology drug discovery is redefining the traditional pipeline by accelerating discovery, optimizing drug efficacy, and minimizing toxicity. AI has enabled groundbreaking advancements in molecular modeling, simulation techniques, and the identification of novel compounds, including anti-tumor and antibodies, while elucidating mechanisms of drug toxicity. Additionally, AI has emerged as a critical tool in precision medicine, driving the formulation and release of targeted therapies and improving the development of treatments for oncology and central nervous system diseases. Furthermore, AI-assisted clinical trial designs have further optimized the recruitment and stratification of patients, reducing the time and cost of trials. Despite these advancements, challenges such as data integration, transparency, and ethical considerations persist. By synthesizing current innovations, this manuscript provides a comprehensive analysis of AI-driven approaches in drug discovery and their potential to advance oncology therapeutics and precision medicine. It examines the transformative role of AI across the drug development continuum, with a focus on its applications in computer-aided drug design (CADD), generative artificial intelligence (GAI), and high-throughput screening (HTS).

The role of gut microbial dysbiosis in chemotherapy-induced diarrhea (CID) pathogenesis remains unclear in humans. This study investigates gut microbiota alterations in CID patients and evaluates the therapeutic potential of probiotic supplementation.

Biologically active heterocycles hold considerable potential in modulating cellular pathways associated with cancer progression. The present study focuses on the design and synthesis of novel thiadiazole-thiazolidinone hybrid scaffolds aimed at inhibiting the proliferation of cancer cells. The synthesized compounds were evaluated for their cytotoxic efficacy against human cancer cell lines, including HepG2 (hepatocellular carcinoma), MCF-7 (breast adenocarcinoma), HCT-116 (colorectal carcinoma), and W138 (lung fibroblast-derived carcinoma). Doxorubicin was used as a reference standard. Among the synthesized library, compound 7 demonstrated the most potent antiproliferative activity across all tested cell lines, indicating its potential role in targeting molecular pathways involved in tumor growth and survival. To elucidate the underlying mechanism of action, molecular docking studies were conducted to analyze ligand-target interactions at the atomic level, revealing favorable binding conformations within key regulatory proteins implicated in oncogenesis. Furthermore, enzyme kinetics and dose-response inhibition assays were performed to characterize the interaction dynamics and establish potential modes of inhibition. The ADMET profile of the lead compounds was also evaluated in silico, supporting their drug-likeness and safety for further preclinical development. These findings contribute valuable scaffolds for the development of new anticancer agents and highlight the importance of integrating chemical synthesis with molecular biology techniques in the discovery of targeted cancer therapeutics.

Transarterial chemoembolization (TACE) is a common clinical intervention used for unresectable liver tumors, but conventional embolic microspheres generally exhibit slack vascular stacking and suboptimal drug release. Here, we report tumor vessel-adaptable, adhesive, and absorbable microspheres (3Asphere) based on hyaluronic acid developed using microfluidic and radical polymerization techniques for sustained TACE therapy of liver tumors. 3Asphere presents uniform sizes, gradual degradation over two months, and fast encapsulation and sustained release of chemotherapeutics such as epirubicin, irinotecan, and cisplatin. Interestingly, 3Asphere with high elasticity enables robust vascular embolization, effectively blocking rabbit renal blood supply for over one month. In rabbit VX2 orthotopic liver tumors, 3Asphere actively binds to endothelial cells via CD44 and inhibits tumor growth, affording significant survival benefits compared to commercial Embosphere®. TACE with epirubicin-loaded 3Asphere further enhances tumor inhibition and prevents lung metastasis. 3Asphere provides a versatile and advanced TACE therapy that might alleviate liver tumors.

Anticancer drug 5FU is extensively metabolized by dihydropyrimidine dehydrogenase (DPD), an enzyme with high interindividual variability. Poor metabolizer (PM, i.e., DPD deficient) patients are at risk of life-threatening toxicities. Whether ultra-rapid metabolizer (UM) status could conversely compromise 5FU efficacy remains to be investigated.

Although neoadjuvant chemoimmunotherapy has emerged as a promising approach for resectable non-small cell lung cancer (NSCLC), comparative real-world data on different PD-1 inhibitors are limited. This study compared the clinical efficacy, pathological response, survival, and safety of four PD-1 inhibitors-pembrolizumab, tislelizumab, camrelizumab, and sintilimab-in patients with Stage II-IIIa NSCLC.

PARP1 has been shown to regulate EBV latency. However, the therapeutic effect of PARP1 inhibitors on EBV+ lymphomagenesis has not yet been explored. Here, we show that PARPi BMN 673 has a potent antitumor effect on EBV-driven LCL in a mouse xenograft model. We found that PARP1 inhibition induces a dramatic transcriptional reprogramming of LCLs driven largely by the reduction of the MYC oncogene expression and dysregulation of MYC targets, both in vivo and in vitro. PARP1 inhibition also reduced the expression of viral oncoprotein EBNA2, which we previously demonstrated depends on PARP1 for activation of MYC. Further, we show that PARP1 inhibition blocks the chromatin association of MYC, EBNA2, and tumor suppressor p53. Overall, our study strengthens the central role of PARP1 in EBV malignant transformation and identifies the EBNA2/MYC pathway as a target of PARP1 inhibitors and its utility for the treatment of EBNA2-driven EBV-associated cancers.

Hand-foot syndrome (HFS) is the most common adverse effect of capecitabine.

Corticosteroids are frequently prescribed to patients with non-small cell lung cancer (NSCLC) for palliation of cancer-related symptoms; however, the potential impact of baseline steroid use on immune checkpoint inhibitor (ICI) therapy and its underlying mechanisms remain unclear. In this study, we evaluated clinical outcomes of 277 patients with NSCLC treated with ICI therapy at two academic institutions. Twenty-one patients (8%) were taking steroids at the start of ICIs. Patients on baseline steroids had a lower overall response rate with markedly shorter progression-free survival and overall survival compared with those not receiving steroids. In multivariate analysis, steroid use was the only significant independent risk factor for disease progression and mortality in both independent cohorts, Roswell Park Comprehensive Cancer Center (n = 88) and University of Southern California (n = 189). A baseline peripheral blood neutrophil-to-lymphocyte ratio <5 was a strong prognostic indicator; however, the prognostic value of neutrophil-to-lymphocyte ratio was absent in patients receiving steroids. Additionally, the baseline frequency of circulating CX3CR1+CD8+ T cells was substantially lower in patients on steroids. Using a bedside-to-bench approach, we found that concurrent steroid use significantly decreased antitumor efficacy of anti-PD-1 therapy and attenuated the increase of CX3CR1+CD8+ T cells in mice bearing MC38 tumors whereas discontinuation of steroid at the start of treatment did not make a negative impact on survival. Collectively, baseline steroid use was associated with worse outcomes and decreased frequency of circulating differentiated effector T cells in patients with NSCLC. Caution should be taken when interpreting the results from circulating immune-related biomarkers in patients on steroids.

Despite significant attention in the media and oncology community about improved outcomes associated with immune checkpoint inhibitors (ICIs), there remains a gap in our understanding of how oncologists describe ICIs to their patients. Communication around ICIs represents a challenge as some patients have durable, remarkable benefits while others experience severe toxicities. We investigated oncologist-patient communication practices by performing a mixed-methods study of in-clinic discussions about ICIs.

Mature tertiary lymphoid structures (TLSs) are immune aggregates associated with immune checkpoint blockade (ICB) responses in various cancers, yet their role in chemoimmunotherapy response in head and neck squamous cell carcinoma (HNSCC) remains unclear. By analyzing TCGA-HNSC transcriptomic data and pathology slides, we identified an immune subtype enriched in TLSs, predominantly in HPV-positive tumors, which correlated with favorable immunotherapy response. Single-cell and spatial transcriptomics further revealed distinct TLS compositions, with mature TLSs enriched in germinal center B cells, follicular helper T cells, and resident memory CD8 T cells, while immature TLSs contained FCRL4+ B cells and peripheral helper T cells. Multispectral immunohistochemistry, flow cytometry, and ELISA validated these findings. Notably, neoadjuvant chemoimmunotherapy promoted mature TLS formation. These results suggest that TLS maturity correlates with HPV status and response to anti-PD-1-based chemoimmunotherapy, providing insights for potential therapeutic strategies in HNSCC.

Psoriasis is a chronic inflammatory skin disease associated with multisystem comorbidities and impaired mental health. The lesions are typically characterized by sharply demarcated, erythematous plaques covered with silvery scales. Treatment options include topical agents, phototherapy, systemic therapies, and biologic agents. Traditional systemic treatments are generally contraindicated in patients with cancer due to their immunosuppressive effects. Although biologics are widely used in the management of psoriasis, their safety in patients with malignancy remains insufficiently evaluated, as individuals with cancer are typically excluded from clinical trials due to concerns about cancer progression. We report the case of a 61-year-old man whose psoriasis markedly worsened following treatment with sintilimab for pulmonary metastases secondary to colon cancer. The patient was successfully treated with guselkumab, an interleukin (IL)-23 inhibitor, resulting in significant improvement in psoriasis symptoms, while the pulmonary condition remained stable during follow-up after completion of standard cancer therapy. This case highlights the potential utility of IL-23 inhibitors as safe and effective treatment options for patients with concomitant psoriasis and malignancy.

Our goal was to assess the efficacy of integrating PD-1 inhibitors with total neoadjuvant treatment (iTNT) in enhancing complete response (CR) rates and the propensity for watch-and-wait (WW) strategies in patients with proficient mismatch repair or microsatellite stable (pMMR/MSS) locally advanced rectal cancer (LARC).

Immune checkpoint inhibitors have improved survival in patients with recurrent or metastatic cervical cancer (r/mCC), yet reliable predictors of treatment efficacy remain undefined. Immune-related adverse events (irAEs) have been suggested as potential predictors of response, but evidence in cervical cancer is limited.

The increasing threat of antimicrobial resistance and cancer has driven the search for new therapeutic agents, with plant-based biosynthesis of nanoparticles emerging as a promising approach. Silver nanoparticles (AgNPs) synthesized from plant extracts have gained attention for their potential biomedical applications.

The current treatment of hepatocellular carcinoma (HCC) is confronted with anoxic drug resistance and significant side effects. To address these issues, a Reactive Oxygen Species (ROS)-responsive and targeted nano drug delivery system named REG/YC-1@PTP-RGD NPs (RYP-RGD NPs) was designed for the co-delivery of Regorafenib (REG) and the hypoxia inhibitor 3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole (YC-1).

The treatment of cancer remains a formidable challenge, largely due to the difficulty in achieving efficient co-delivery of chemotherapeutic and immunotherapeutic agents to specific tumor sites. Nanosuspension-based biomaterial drug delivery systems for anti-cancer (NBDDSC) have emerged as promising platforms for enhancing drug solubility, stability, and targeted delivery. These systems can be categorized into natural polymer-based, synthetic polymer-based, and hybrid nanosuspensions, each offering distinct advantages in biocompatibility, drug loading, and controlled release. However, the majority of existing NBDDSC rely on synthetic materials that function primarily as excipients, offering no intrinsic therapeutic value. These materials often require intricate manufacturing processes, which can result in issues with batch consistency, reduced stability, and diminished therapeutic efficacy. Additionally, the potential side effects associated with synthetic components further underscore the limitations of these systems. This review explores various preparation methods for nanosuspensions, including antisolvent precipitation, high pressure homogenization, and ultrasonication, highlighting their impact on particle size, drug encapsulation, and stability. Furthermore, the targeted applications of these nanosuspensions in treating of cancers such as glioma is discussed to emphasize their potential clinical relevance. By addressing current limitations, this review underscores the critical importance of simpler, safer, and clinically translatable NBDDSC in advancing cancer therapy.

Doxorubicin (DOX) is an anthracycline chemotherapeutic agent widely used for treating various malignancies due to its remarkable efficacy. However, the dose-limiting cardiotoxicity induced by DOX remains a critical clinical concern with limited therapeutic strategy. Several molecular mechanisms underlying the pathogenesis of doxorubicin-induced cardiotoxicity (DIC) have been proposed, including oxidative stress, dysregulation of Top2β, mitochondrial damage, imbalance of calcium homeostasis, ferroptosis, and inflammatory responses. Increasing studies have posed the promise of the natural products flavonoids against DIC attributed to its advantages in antioxidant activity as well as anti-cancer properties. This paper reviews relevant publications to date and comprehensively summarizes the evidence from preclinical and clinical studies in support of the cardioprotective effect of seven flavonoids subclasses against DIC, including flavones with 18 compounds, flavonols with 11 compounds, isoflavones with 7 compounds, flavanones with 6 compounds, chalcones with 3 compounds, flavanols with 2 compounds and anthocyanins with 2 compounds. Specially, several lines of evidence have also demonstrated the anti-cancer property of flavonoids in addition to the cardioprotective property. This review synthesizes comprehensive mechanistic and translational insights to inform future preclinical and clinical investigations aiming at integrating flavonoid-based interventions into oncotherapeutic regimens. The accumulated evidence underscores flavonoids as promising candidates for DIC as well as adjuvant cancer therapy.