The mitotic inhibitor docetaxel (DTX) is often used to treat endocrine-refractory metastatic breast cancer, but initial responses are mitigated as patients develop disease progression. Using a cohort of ex vivo cultured circulating tumor cells (CTCs) from patients with heavily pretreated breast cancer (n=18), we find distinct patterns of response to DTX, which are intrinsic and independent of past clinical treatment with taxanes. In some CTC cultures, treatment with a single dose of DTX results in complete cell killing, associated with accumulation of nonviable polyploid (≥8 N) cells arising from endomitosis. In other CTC cultures, a transient viable drug-tolerant persister (DTP) population emerges, ultimately enabling renewed proliferation of CTCs with preserved parental cell ploidy and restored DTX sensitivity identical to that of the pretreated culture. In these CTCs, efficient cell cycle exit generates a ≤4 N drug-tolerant state dependent on CDKN1B (p27/kip1). Exposure to DTX triggers stabilization of CDKN1B through AKT-mediated phosphorylation at serine 10. Suppression of CDKN1B reduces the number of persister CTCs, increases ≥8 N mitotic cells and abrogates regrowth after DTX exposure. Thus, CDKN1B-mediated suppression of endomitosis contributes to the initiation of a reversible drug-tolerant persister state following mitotic inhibitors in advanced patient-derived breast cancer cells.

This study demonstrates the utility of a rat model of chemotherapy-induced peripheral neuropathy (CIPN) to assess the ability of the non-psychoactive cannabinoid cannabidiol (CBD) to modulate the development of this syndrome in vivo. The method utilizes the chemotherapeutic agent paclitaxel to generate an allodynic phenotype in the animals. This study describes how to handle and solubilize CBD, administer the chemotherapeutic agent, assess mechanical and cold sensitivity, and apply high-speed videography to measure nocifensive behavior in animals. Using the procedures outlined, the data support that CBD prevents the allodynic phenotype from developing in the treated animals. No difference was observed in the CBD-treated animals from day 0 (pre-paclitaxel baseline) to day 7 (post-sensitization) in mechanical or thermal sensitivity, while the vehicle-treated animals became significantly more sensitive. This response to treatment is durable up to the latest time point where data were collected (7 weeks). The addition of high-speed videography allows for a more granular and unbiased assessment of this behavioral phenotype (e.g., classification of analgesia and anti-allodynia). This demonstrates both the utility of this model for cannabinoid drug characterization and the potential role of CBD in mitigating neuropathic pain.

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.

In the literature, it is seen that heteroaromatic imidazole compounds have many effective biological properties such as antitumor, antimicrobial, antioxidant, antihypertensive, antiallergic, anticancer, analgesic and anti-inflammatory. Due to these effects, its therapeutic effects in various types of cancer are being investigated more and more day by day. In particular, the effects of imidazole derivatives are being investigated for cancer types for which no treatment has yet been identified, such as Glioblastoma Multiforme (GBM). For this reason, the anticancer effects of imidazole derivatives on U-87 MG and HDFa cells, their inhibitory effects on TrxR1, GR and GST enzymes associated with multidrug resistance in cancer cells, and their antioxidant and antimicrobial activities were investigated. Cytotoxic effects were measured by MTT assay after U-87 MG HDFa cells were treated with imidazole compounds. The results revealed that imidazole compounds decreased the viability of cells in a dose-dependent manner compared to the control group. In addition, when imidazole compounds are used in treatments targeting enzymes in cancerous cells, it has been observed that they do not harm healthy HDFa cells, but they also have a significant effect on U-87 MG cells. It can be said that compound I3 is a selective inhibitor in the treatment of Glioblastoma. It was observed that compounds I2 and I3 have antimicrobial activity. When the antioxidant activities of imidazole derivatives were examined, we observed that compounds I2 and I3 exhibited antioxidant activity. These results show us that imidazole molecules have antioxidant, antimicrobial and anticancer effects.

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.

Artemisinin, found in the traditional Chinese medicine (TCM) Artemisia annua, has demonstrated remarkable efficacy in therapeutics and holds significant potential as a pharmaceutical drug in cancer. Until now, there have been no systematic scientometrics studies to analyze the research trend of artemisinin and its derivatives in cancer.

Small cell lung cancer (SCLC) is a highly aggressive disease associated with poor patient survival rates. The addition of an anti-programmed death ligand 1 antibody to platinum combination chemotherapy can improve its prognosis. However, only a few patients achieve a long-term response; thus, establishing new therapies for SCLC is crucial. Midkine (MDK) is a heparin-binding growth factor involved in various biological processes, including cell proliferation and chemotherapeutic resistance, in diverse cancers. MDK has garnered attention as a therapeutic and diagnostic target for several cancers; however, only a few studies have evaluated its expression and function in SCLC. This study aimed to evaluate the MDK expression in human SCLC tissue and human SCLC cell lines, and to clarify its function in tumorigenesis.

Immune checkpoint inhibitors (ICIs) are monoclonal antibodies that block inhibitory pathways that cancer cells exploit to suppress T-cell activation. Although immune-related adverse events (irAEs) linked to ICI therapy are well documented and encompass dermatologic, endocrine, gastrointestinal, hepatic, and neurologic systems, ICI-related dysautonomia remains a rare phenomenon. Management of ICI-related dysautonomia is undefined.

Selenium, an essential micronutrient in the human body, not only exhibits potent antioxidant properties but also plays a critical role in regulating thyroid hormone metabolism, maintaining normal immune function, and inhibiting tumour progression. Among selenium-containing compounds, ebselen is the most extensively studied drug candidate. Research has shown that various derivatives obtained through structural modifications of Ebselen exhibits significant biological activities; however, these compounds have yet to progress to clinical trials. Consequently, selenium-containing heterocyclic compounds represent a promising avenue for drug discovery and development. This review summarizes three synthetic approaches for constructing selenium-containing heterocyclic compounds and emphasizes their notable biological activities and potential applications in pharmaceuticals.

While cancer-associated fibroblasts (CAFs) significantly influence tumor progression, their temporal dynamics remain poorly understood. We investigated time-dependent interactions between non-small cell lung cancer (NSCLC) cells and CAFs, and evaluated rosmarinic acid (RA)'s potential to modulate these interactions. HCC827 lung adenocarcinoma cells and MRC-5 fibroblasts were co-cultured in vitro. CAF activation markers (α-SMA, FAP) and epithelial-mesenchymal transition (EMT) were assessed through morphological and molecular analyses. Xenograft models with different tumor-to-fibroblast ratios (1:1, 1:2) evaluated tumor growth dynamics and RA's therapeutic effects combined with gefitinib. Time-course analysis revealed a biphasic pattern in tumor-CAF interactions. CAF activation markers reached peak levels by day 6, followed by maximal EMT marker expression in NSCLC cells at day 8. In xenograft models, higher CAF proportions initially inhibited tumor growth but accelerated tumor progression. RA treatment significantly attenuated CAF activation markers and reversed EMT-related changes in cancer cells, leading to reduced tumor growth in CAF-enriched xenografts. The combination of RA with gefitinib demonstrated enhanced anti-tumor effects compared to gefitinib alone. CAFs exhibit temporally biphasic roles in NSCLC progression characterized by initial suppression followed by promotion of tumor microenvironment deterioration. RA effectively modulates these tumor-stromal interactions, enhances gefitinib efficacy, and delays the development of drug resistance.